T3D0016 - Trichloroethylene

1. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial

Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (R160)

Q15118

PDK1

SNPJam Report

• R160 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

2. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial

Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (R160)

Q15119

PDK2

SNPJam Report

• R160 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

3. Alcohol dehydrogenase 1A

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P07327

ADH1A

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

4. Alcohol dehydrogenase 1B

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P00325

ADH1B

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

5. Alcohol dehydrogenase 1C

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P00326

ADH1C

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

6. Alcohol dehydrogenase class 4 mu/sigma chain

Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P40394

ADH7

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

7. Alcohol dehydrogenase class-3

Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P11766

ADH5

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

8. Alcohol dehydrogenase 4

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P08319

ADH4

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

9. Alcohol dehydrogenase 6

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Chloral hydrate inhibits alcohol dehydrogenase. (R161)

P28332

ADH6

SNPJam Report

• R161 — Sharkawi M, De Saint Blanquat G, Elfassy B: Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction. Toxicol Lett. 1983 Jul;17(3-4):321-8. [6353674 ]

10. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 3, mitochondrial

Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (R160)

Q15120

PDK3

SNPJam Report

• R160 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

11. [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial

Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.

The toxic and carcinogenic effects of trichloroethylene are believed to be cause mainly by its metabolites, including trichloroacetic acid, dichloroacetic acid, and chloral hydrate. The nephrotoxicity and nephrocarcinogenicity of TRI have been attributed to glutathione conjunction, which forms reactive, sulfur-containing metabolites. Dichloroacetic acid is known to inhibit pyruvate dehydrogenase kinase. (R160)

Q16654

PDK4

SNPJam Report

• R160 — Lantum HB, Baggs RB, Krenitsky DM, Anders MW: Nephrotoxicity of chlorofluoroacetic acid in rats. Toxicol Sci. 2002 Dec;70(2):261-8. [12441371 ]

12. Calcium-transporting ATPase type 2C member 1

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P98194

ATP2C1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

13. Calcium-transporting ATPase type 2C member 2

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium (By similarity).

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

O75185

ATP2C2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

14. Gamma-aminobutyric acid receptor subunit alpha-1

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P14867

GABRA1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

15. Gamma-aminobutyric acid receptor subunit alpha-2

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P47869

GABRA2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

16. Gamma-aminobutyric acid receptor subunit alpha-3

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P34903

GABRA3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

17. Gamma-aminobutyric acid receptor subunit alpha-4

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P48169

GABRA4

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

18. Gamma-aminobutyric acid receptor subunit alpha-5

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P31644

GABRA5

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

19. Gamma-aminobutyric acid receptor subunit alpha-6

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

Q16445

GABRA6

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

20. Gamma-aminobutyric acid receptor subunit beta-1

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P18505

GABRB1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

21. Gamma-aminobutyric acid receptor subunit beta-2

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P47870

GABRB2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

22. Gamma-aminobutyric acid receptor subunit beta-3

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P28472

GABRB3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

23. Gamma-aminobutyric acid receptor subunit delta

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

O14764

GABRD

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

24. Gamma-aminobutyric acid receptor subunit epsilon

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P78334

GABRE

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

25. Gamma-aminobutyric acid receptor subunit gamma-1

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

Q8N1C3

GABRG1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

26. Gamma-aminobutyric acid receptor subunit gamma-2

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P18507

GABRG2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

27. Gamma-aminobutyric acid receptor subunit gamma-3

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

Q99928

GABRG3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

28. Gamma-aminobutyric acid receptor subunit pi

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

O00591

GABRP

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

29. Gamma-aminobutyric acid receptor subunit rho-1

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P24046

GABRR1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

30. Gamma-aminobutyric acid receptor subunit rho-2

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

P28476

GABRR2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

31. Gamma-aminobutyric acid receptor subunit rho-3

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel (By similarity).

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

A8MPY1

GABRR3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

32. Gamma-aminobutyric acid receptor subunit theta

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

This organochloride antagonizes the action of the neurotransmitter gamma-aminobutyric acid (GABA) acting at the GABA-A receptors, effectively blocking the GABA-induced uptake of chloride ions and causing hyperexcitability of the central nervous system. (R029)

Q9UN88

GABRQ

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

33. Plasma membrane calcium-transporting ATPase 1

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P20020

ATP2B1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

34. Plasma membrane calcium-transporting ATPase 2

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

Q01814

ATP2B2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

35. Plasma membrane calcium-transporting ATPase 3

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

Q16720

ATP2B3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

36. Plasma membrane calcium-transporting ATPase 4

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P23634

ATP2B4

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

37. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

O14983

ATP2A1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

38. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P16615

ATP2A2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

39. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

Q93084

ATP2A3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

40. Sodium/potassium-transporting ATPase subunit gamma

May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P54710

FXYD2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

41. Sodium/potassium-transporting ATPase subunit alpha-1

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P05023

ATP1A1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

42. Sodium/potassium-transporting ATPase subunit alpha-2

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P50993

ATP1A2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

43. Sodium/potassium-transporting ATPase subunit alpha-3

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P13637

ATP1A3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

44. Sodium/potassium-transporting ATPase subunit alpha-4

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

Q13733

ATP1A4

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

45. Sodium/potassium-transporting ATPase subunit beta-1

This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P05026

ATP1B1

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

46. Sodium/potassium-transporting ATPase subunit beta-2

This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P14415

ATP1B2

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

47. Sodium/potassium-transporting ATPase subunit beta-3

This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.

This organochloride inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (R029)

P54709

ATP1B3

SNPJam Report

• R029 — Casarett LJ, Klaassen CD, and Watkins JB (2003). Casarett and Doull's essentials of toxicology. New York: McGraw-Hill/Medical Pub. Div.

48. Estrogen receptor

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)

P03372

ESR1

SNPJam Report

• S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.

49. Estrogen receptor beta

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)

Q92731

ESR2

SNPJam Report

• S301 — Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors ? and ?: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.