SULT1A3

Summary

SULT1A3 (sulfotransferase family 1A member 3, HGNC:11455) is a protein-coding gene on chromosome 16p11.2, encoding Sulfotransferase 1A3 (P0DMM9). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, (R)-adrenaline/epinephrine, (R)-noradrenaline/norepinephrine and serotonin) and phenolic and ca….

Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes a phenol sulfotransferase with thermolabile enzyme activity. Four sulfotransferase genes are located on the p arm of chromosome 16; this gene and SULT1A4 arose from a segmental duplication. This gene is the most centromeric of the four sulfotransferase genes. Read-through transcription exists between this gene and the upstream SLX1A (SLX1 structure-specific endonuclease subunit homolog A) gene that encodes a protein containing GIY-YIG domains.

Source: NCBI Gene 6818 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• MANE Select transcript: NM_177552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11455
Approved symbol	SULT1A3
Name	sulfotransferase family 1A member 3
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	TL-PST
Ensembl gene	ENSG00000261052
Ensembl biotype	protein_coding
OMIM	600641
Entrez	6818

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000338971, ENST00000395138, ENST00000561533, ENST00000561549, ENST00000562257, ENST00000563322, ENST00000563638, ENST00000567309, ENST00000569409, ENST00000569485, ENST00000857351, ENST00000857352, ENST00000857353, ENST00000857354, ENST00000857355, ENST00000960950, ENST00000960951, ENST00000960952

RefSeq mRNA: 2 — MANE Select: NM_177552 NM_001421666, NM_177552

CCDS: CCDS10674

Canonical transcript exons

ENST00000338971 — 8 exons

Exon	Start	End
ENSE00002608462	30199255	30199327
ENSE00003714298	30203505	30203685
ENSE00003720709	30202690	30202816
ENSE00003737063	30200981	30201106
ENSE00003742981	30200725	30200876
ENSE00003744435	30201196	30201293
ENSE00003754067	30202912	30203006
ENSE00003902183	30203808	30204310

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.98.

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	98.98	gold quality
mucosa of transverse colon	UBERON:0004991	98.24	gold quality
granulocyte	CL:0000094	97.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.68	gold quality
small intestine	UBERON:0002108	95.01	gold quality
lower esophagus mucosa	UBERON:0035834	94.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.56	gold quality
spleen	UBERON:0002106	94.44	gold quality
cerebellar hemisphere	UBERON:0002245	94.39	gold quality
rectum	UBERON:0001052	94.29	gold quality
transverse colon	UBERON:0001157	94.29	gold quality
cerebellar cortex	UBERON:0002129	94.18	gold quality
cerebellum	UBERON:0002037	94.04	gold quality
right lobe of liver	UBERON:0001114	94.02	gold quality
right lobe of thyroid gland	UBERON:0001119	93.09	gold quality
pituitary gland	UBERON:0000007	92.42	gold quality
metanephros cortex	UBERON:0010533	92.28	gold quality
left lobe of thyroid gland	UBERON:0001120	92.20	gold quality
intestine	UBERON:0000160	92.18	gold quality
leukocyte	CL:0000738	92.15	gold quality
adenohypophysis	UBERON:0002196	92.07	gold quality
monocyte	CL:0000576	92.01	gold quality
omental fat pad	UBERON:0010414	91.84	gold quality
thyroid gland	UBERON:0002046	91.81	gold quality
blood	UBERON:0000178	91.41	gold quality
colon	UBERON:0001155	91.33	gold quality
right uterine tube	UBERON:0001302	91.25	gold quality
adipose tissue	UBERON:0001013	91.23	gold quality
minor salivary gland	UBERON:0001830	90.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.93	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	366.92
E-HCAD-6	yes	43.76
E-GEOD-125970	yes	18.80
E-ANND-3	yes	3.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, DRD1, GABPA, MAPK1, MAPK3, SP1

Literature-anchored findings (GeneRIF, showing 29)

• M-PST is involved in protective and detoxification mechanisms that may operate in neurodegenerative processes in the brain (PMID:12228221)
• structure-function relationships in the stereospecific and manganese-dependent 3,4-dihydroxyphenylalanine/tyrosine-sulfating activity of human monoamine-form phenol sulfotransferase, SULT1A3 (PMID:12424257)
• the differential substrate specificity of the two enzymes M-PST and P-PST for the thirteen drug compounds tested (PMID:12761191)
• Eight single nucleotide polymorphisms were observed in African American[AA] and five in Caucasian-American subjects, including one (Lys234Asn) that was observed only in AA subjects with an allele frequency of 4.2% (PMID:14622112)
• For SULT1A3, substrate inhibition is found for dopamine but not with pNP. Based on modeling and kinetic studies, it is proposed that substrate inhibition by dopamine in SULT1A3 is caused by binding of two dopamine molecules in the active site. (PMID:14871892)
• 2 SULT1A3 genes were present on chromosome 16 in all DNA samples studied. (PMID:15358107)
• X-ray crystallographic analysis of SULT1A3 complexed with dopamine and 3’-phosphoadenosine 5’-phosphate (PMID:16083857)
• Of the 11 human cytosol sulfotransferase enzymes tested, only SULT1A3 displayed sulfating activity toward nitrotyrosine. The pH-dependence and kinetic constants of SULT1A3 with nitrotyrosine or dopamine as substrate were determined. (PMID:17002600)
• data from this study shows that the human SULT1A3 gene is inducible by glucocorticoids through a glucocorticoid receptor-mediated mechanism and the glucocorticoid response element at position (-1211 to -1193) is necessary for this induction. (PMID:17963788)
• Concerted action of cytosolic sulfotransferase, SULT1A3, and catechol-O-methyltransferase in the metabolism of dopamine in SK-N-MC human neuroblastoma cells. SULT1A3 is the major enzyme responsible for the sulfation of both dopamine and 3-methyldopamine. (PMID:19447296)
• SULT1A3 has a role in the inactivation of excess chlorotyrosine and nitrotyrosine during inflammation in lung endothelial and epithelial cells. (PMID:21168432)
• Studies indicate that SULT1A3 is the main isoform responsible for flavonoid sulfonation in the Caco-2 cells. (PMID:22352375)
• The expression of ALDOA and/or SULT1A3 is significantly higher. (PMID:22949271)
• Data indicate that protein-ligand interaction energy by using docking Quantitative Structure-Activity Relationships(QSAR) models showed accuracy of 67.28%, 78.00% and 75.46%, for the isoforms SULT1A1, SULT1A3 and SULT1E1, respectively. (PMID:24039991)
• Taken together, these results show that dopamine can induce its own metabolism and protect neuron-like cells from damage, suggesting that SULT1A3 activity may be a risk factor for dopamine-dependent neurodegenerative diseases. (PMID:24136195)
• The common SULT1A3 single-nucleotide polymorphism 105A>G is not an important determinant of salbutamol enantiomer pharmacokinetics under normal clinical use and does not place some individuals at greater risk of accumulation in the body. (PMID:24692077)
• Genetic polymorphism of SULT1A3,a major ritodrine-sulfating SULT, appeared to exert a dramatic effect on the sulfating activity of SULT1A3 allozymes. (PMID:25941087)
• A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. (PMID:26067475)
• This study aimed to establish SULT1A3 stably transfected HEK293 cells, and to determine the contributions of BCRP and MRP transporters to excretion of chrysin and apigenin sulfates. (PMID:26291395)
• Sulfate metabolites R-6-S and R-4’-S were generated from raloxifene in SULT293 expression HEK293 cells. Cellular excretion of the raloxifene sulfates was mainly mediated by BCRP and MRP4. (PMID:26611713)
• The present study revealed SULT1A3 as the major human SULT enzyme capable of sulfating dextrorphan (PMID:27582324)
• In Alzheimer’s disease patients, there was a significantly lower copy number in SULT1A3 genes compared to controls. (PMID:28374858)
• analysis of the catechin-binding site of SULT1A3 (PMID:28630292)
• Our results implied that SULT1A3/4 exhibited bidirectional effect on tumor and normal hepatocytes and may thus provide a novel strategy for hepatocellular carcinoma clinical targeting. In addition, SULT1A3/4 re-expression could serve as a biomarker for hepatocellular carcinoma prognosis. (PMID:29025375)
• Effects of human SULT1A3/SULT1A4 genetic polymorphisms on the sulfation of acetaminophen and opioid drugs by the cytosolic sulfotransferase SULT1A3 (PMID:29705271)
• The results obtained showed clearly the differential enzymatic characteristics of SULT1A3 allozymes in mediating the sulfation of phenylephrine and salbutamol. This information may contribute toward a better understanding of the pharmacokinetics of these two drugs in individuals with distinct SULT1A3 and/or SULT1A4 genotypes. (PMID:31145702)
• Interaction of the Brain-Selective Sulfotransferase SULT4A1 with Other Cytosolic Sulfotransferases: Effects on Protein Expression and Function. (PMID:32152050)
• Farnesoid X receptor represses human sulfotransferase 1A3 expression through direct binding to the promoter. (PMID:37487659)
• Role of Conformational Dynamics of Sulfotransferases SULT1A1 and SULT1A3 in Substrate Specificity. (PMID:38069221)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult1st4	ENSDARG00000003181
danio_rerio	sult5a1	ENSDARG00000007769
danio_rerio	sult1st3	ENSDARG00000018361
danio_rerio	sult1st1	ENSDARG00000028275
danio_rerio	sult2st3	ENSDARG00000028367
danio_rerio	sult2st1	ENSDARG00000033170
danio_rerio	sult1st2	ENSDARG00000041540
danio_rerio	sult1st7	ENSDARG00000079079
danio_rerio	sult1st9	ENSDARG00000094996
danio_rerio	sult2st2	ENSDARG00000103785
mus_musculus	Sult5a1	ENSMUSG00000000739
rattus_norvegicus	Sult5a1	ENSRNOG00000015695
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2B1 (ENSG00000088002), SULT2A1 (ENSG00000105398), SULT1E1 (ENSG00000109193), SULT4A1 (ENSG00000130540), SULT6B1 (ENSG00000138068), SULT1B1 (ENSG00000173597), SULT1C3 (ENSG00000196228), SULT1A1 (ENSG00000196502), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648)

Protein

Protein identifiers

Sulfotransferase 1A3 — P0DMM9 (reviewed: P0DMM9)

Alternative names: Aryl sulfotransferase 1A3/1A4, Catecholamine-sulfating phenol sulfotransferase, HAST3, M-PST, Monoamine-sulfating phenol sulfotransferase, Placental estrogen sulfotransferase, Sulfotransferase 1A3/1A4, Sulfotransferase, monoamine-preferring, Thermolabile phenol sulfotransferase

All UniProt accessions (4): P0DMM9, H3BPL6, H3BRT0, Q1ET61

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, (R)-adrenaline/epinephrine, (R)-noradrenaline/norepinephrine and serotonin) and phenolic and catechol drugs. Catalyzes the sulfation of T4 (L-thyroxine/3,5,3’,5’-tetraiodothyronine), T3 (3,5,3’-triiodothyronine), rT3 (3,3’,5’-triiodothyronine) and 3,3’-T2 (3,3’-diiodothyronine), with a substrate preference of 3,3’-T2 > rT3 > T3 > T4.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Liver, colon, kidney, lung, brain, spleen, small intestine, placenta and leukocyte.

Post-translational modifications. The N-terminus is blocked.

Similarity. Belongs to the sulfotransferase 1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P0DMM9-1	1	yes
P0DMM9-2	2
P0DMM9-3	3

RefSeq proteins (2): NP_001408595, NP_808220* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Enzyme classification (BRENDA):

• EC 2.8.2.1 — aryl sulfotransferase (BRENDA: 19 organisms, 630 substrates, 215 inhibitors, 314 Km, 55 kcat entries)

Substrate kinetics (BRENDA)

81 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DOPAMINE	0.0006–11.3	39
4-NITROPHENOL	0.0001–30.9	36
3’-PHOSPHOADENYLYLSULFATE	0.0003–0.51	17
ACETAMINOPHEN	0.43–4.5	14
MORPHINE	3.8–10	13
O-DESMETHYL TRAMADOL	0.27–0.8	13
TAPENTADOL	0.09–0.84	13
3’-PHOSPHOADENYLYL SULFATE	0.0008–0.024	12
DAIDZEIN	0.0005–0.407	8
GENISTEIN	0.0005–0.371	8
6-HYDROXYMELATONIN	0.018–0.065	6
7-HYDROXYCOUMARIN	0.0005–0.003	4
ROTIGOTINE	0.0291–0.1191	4
2-AMINOPHENOL	0.009–0.223	3
3,3’,5-TRIIODO-L-THYRONINE	0.0387–0.126	3

Catalyzed reactions (Rhea), 11 shown:

• a phenol + 3’-phosphoadenylyl sulfate = an aryl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:12164)
• 4-nitrophenol + 3’-phosphoadenylyl sulfate = 4-nitrophenyl sulfate + adenosine 3’,5’-bisphosphate (RHEA:66548)
• 3,3’,5-triiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’,5-triiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67876)
• dopamine + 3’-phosphoadenylyl sulfate = dopamine 3-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67880)
• dopamine + 3’-phosphoadenylyl sulfate = dopamine 4-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67884)
• 3,3’,5’-triiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’,5’-triiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67888)
• 3,3’-diiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’-diiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67892)
• serotonin + 3’-phosphoadenylyl sulfate = serotonin O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:83339)
• (R)-adrenaline + 3’-phosphoadenylyl sulfate = (R)-adrenaline 4’-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:83343)
• (R)-noradrenaline + 3’-phosphoadenylyl sulfate = (R)-noradrenaline 4’-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:83351)
• L-thyroxine + 3’-phosphoadenylyl sulfate = L-thyroxine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:83575)

UniProt features (57 total): helix 16, sequence variant 10, binding site 9, strand 6, turn 6, sequence conflict 4, splice variant 2, mutagenesis site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1CJM	X-RAY DIFFRACTION	2.4
2A3R	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMM9-F1	96.62	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 108 (proton acceptor)

Ligand- & substrate-binding residues (9): 257–259; 48–53; 86; 106–108; 130; 138; 146; 193; 227–232

Mutagenesis-validated functional residues (2):

Position	Phenotype
235	a 5-fold increase in km and 3-fold decrease in vmax for (r)-noradrenaline. a 100-fold increase in km and a 3-fold increa
290	a 2-fold increase in km for serotonin.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9748784	Drug ADME

MSigDB gene sets: 90 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, REACTOME_BIOLOGICAL_OXIDATIONS, MODULE_274, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MODULE_308, GOBP_SULFATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, RODRIGUES_NTN1_TARGETS_DN, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MODULE_331

GO Biological Process (15): ethanol catabolic process (GO:0006068), xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), flavonoid metabolic process (GO:0009812), thyroid hormone metabolic process (GO:0042403), epinephrine metabolic process (GO:0042414), norepinephrine metabolic process (GO:0042415), dopamine metabolic process (GO:0042417), dopamine catabolic process (GO:0042420), serotonin metabolic process (GO:0042428), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923), cellular response to dopamine (GO:1903351), catecholamine metabolic process (GO:0006584), lipid metabolic process (GO:0006629)

GO Molecular Function (6): aryl sulfotransferase activity (GO:0004062), sulfotransferase activity (GO:0008146), sulfate binding (GO:0043199), amine sulfotransferase activity (GO:0047685), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
IRE1alpha activates chaperones	1
Drug ADME	1
Biological oxidations	1
Metabolism	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catecholamine metabolic process	3
metabolic process	2
phenol-containing compound metabolic process	2
sulfur compound metabolic process	2
sulfotransferase activity	2
cellular anatomical structure	2
ethanol metabolic process	1
primary alcohol catabolic process	1
cellular response to xenobiotic stimulus	1
lipid metabolic process	1
modified amino acid metabolic process	1
hormone metabolic process	1
dopamine metabolic process	1
catecholamine catabolic process	1
indole-containing compound metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
cellular response to catecholamine stimulus	1
response to dopamine	1
biogenic amine metabolic process	1
catechol-containing compound metabolic process	1
primary metabolic process	1
transferase activity, transferring sulphur-containing groups	1
anion binding	1
sulfur compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT1A3	THBD	P07204	835
SULT1A3	GOT1	P17174	830
SULT1A3	SULT1A1	P50225	745
SULT1A3	STS	P08842	700
SULT1A3	F3	P13726	588
SULT1A3	VWF	P04275	583
SULT1A3	ALB	P02768	557
SULT1A3	PLAT	P00750	507
SULT1A3	PROCR	Q9UNN8	480
SULT1A3	SERPINE1	P05121	475
SULT1A3	SULT2A1	Q06520	435
SULT1A3	UGT1A6	P19224	431
SULT1A3	SELE	P16111	431
SULT1A3	SULT1C2	O00338	427
SULT1A3	SDC1	P18827	418

IntAct

0 interactions, top by confidence:

BioGRID (53): SULT1A3 (Two-hybrid), NIF3L1 (Two-hybrid), KHDRBS2 (Two-hybrid), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A4 (Affinity Capture-MS), SULT1A3 (Positive Genetic), SULT1A3 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00338, O43704, O46503, O75897, P0CC03, P0DMM9, P0DMN0, P15709, P17988, P19217, P22789, P49887, P49888, P49891, P50225, P50226, P50227, P50234, P50235, P50236, P50237, P52840, P52841, P52842, P52843, P52844, P52846, P52847, Q06520, Q29476, Q3T0Y3, Q3UZZ6, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17

Diamond homologs: A0A173GP47, A0A2K5X3B6, G3V9R3, O00338, O35400, O43704, O46503, O46640, O75897, P0DMM9, P0DMN0, P19217, P49887, P49888, P49891, P50236, P50237, P52839, P52840, P52842, P52844, P52847, P63046, P63047, Q29476, Q3T0Y3, Q3UZZ6, Q6IMI6, Q80VR3, Q8BGL3, Q8JG30, Q95JD5, Q9BR01, Q9C9D0, Q9D939, Q9FZ80, Q9QWG7, Q9WUW8, Q9WUW9, B2RVI8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1197 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30200872:GTCTG:G	donor_gain	1.0000
16:30200874:CTG:C	donor_gain	1.0000
16:30200875:TG:T	donor_gain	1.0000
16:30200875:TGG:T	donor_loss	1.0000
16:30200876:GG:G	donor_gain	1.0000
16:30200876:GGTA:G	donor_loss	1.0000
16:30200877:G:GG	donor_gain	1.0000
16:30200878:T:G	donor_loss	1.0000
16:30200976:TCCA:T	acceptor_loss	1.0000
16:30200977:CCAG:C	acceptor_loss	1.0000
16:30200978:CA:C	acceptor_loss	1.0000
16:30200979:A:AG	acceptor_gain	1.0000
16:30200979:A:AT	acceptor_loss	1.0000
16:30200979:AG:A	acceptor_gain	1.0000
16:30200980:G:GA	acceptor_gain	1.0000
16:30200980:GG:G	acceptor_gain	1.0000
16:30200980:GGC:G	acceptor_gain	1.0000
16:30200980:GGCA:G	acceptor_gain	1.0000
16:30200980:GGCAC:G	acceptor_gain	1.0000
16:30201036:G:GT	donor_gain	1.0000
16:30201057:C:G	donor_gain	1.0000
16:30201103:TCAG:T	donor_loss	1.0000
16:30201105:AGGTG:A	donor_loss	1.0000
16:30201107:G:GG	donor_loss	1.0000
16:30202686:GCA:G	acceptor_loss	1.0000
16:30202687:CA:C	acceptor_loss	1.0000
16:30202688:A:AC	acceptor_loss	1.0000
16:30202688:AGGT:A	acceptor_gain	1.0000
16:30202689:G:GT	acceptor_loss	1.0000
16:30202689:GGTG:G	acceptor_gain	1.0000

AlphaMissense

1952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30203673:T:C	F255L	0.991
16:30203675:C:A	F255L	0.991
16:30203675:C:G	F255L	0.991
16:30200872:G:C	K48N	0.990
16:30200872:G:T	K48N	0.990
16:30200981:G:T	G50V	0.989
16:30202716:G:C	K133N	0.989
16:30202716:G:T	K133N	0.989
16:30202789:T:C	F158L	0.988
16:30202791:C:A	F158L	0.988
16:30202791:C:G	F158L	0.988
16:30202926:T:A	W172R	0.987
16:30202926:T:C	W172R	0.987
16:30202741:T:C	F142L	0.986
16:30202743:C:A	F142L	0.986
16:30202743:C:G	F142L	0.986
16:30202801:T:C	F162L	0.986
16:30202803:C:A	F162L	0.986
16:30202803:C:G	F162L	0.986
16:30203538:T:C	F210L	0.986
16:30203540:T:A	F210L	0.986
16:30203540:T:G	F210L	0.986
16:30201239:G:C	K106N	0.982
16:30201239:G:T	K106N	0.982
16:30203681:G:C	R257S	0.982
16:30203681:G:T	R257S	0.982
16:30203822:T:A	W264R	0.982
16:30203822:T:C	W264R	0.982
16:30200981:G:A	G50D	0.980
16:30201243:C:G	H108D	0.980

dbSNP variants (sampled 300 via entrez): RS1005284345 (16:30197850 C>G), RS1012475256 (16:30197522 A>G), RS1014971225 (16:30197882 G>A), RS1029479460 (16:30201046 C>T), RS1049757961 (16:30197657 A>C), RS1056158142 (16:30204079 T>A), RS1056525105 (16:30197453 T>G), RS1059667 (16:30204300 T>A), RS112327790 (16:30201854 C>T), RS1156277520 (16:30200768 TA>T), RS1156506191 (16:30203717 G>A), RS1156579943 (16:30201974 C>T), RS1158224210 (16:30204717 A>G), RS1158557821 (16:30204638 C>T), RS1158658024 (16:30200838 G>A)

Disease associations

OMIM: gene MIM:600641 | disease phenotypes: MIM:615401

GenCC curated gene-disease

Mondo (1): severe combined immunodeficiency due to CORO1A deficiency (MONDO:0014168)

Orphanet (1): Severe combined immunodeficiency due to CORO1A deficiency (Orphanet:228003)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1743293 (SINGLE PROTEIN), CHEMBL3542433 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

34 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1293732453	Metabolism/PK	3	acetaminophen
rs1293732453	Metabolism/PK	3	morphine
rs1293732453	Metabolism/PK	3	tapentadol
rs1293732453	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs1328799050	Metabolism/PK	3	acetaminophen
rs1328799050	Metabolism/PK	3	morphine
rs1328799050	Metabolism/PK	3	tapentadol
rs1328799050	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs553050853	Metabolism/PK	3	acetaminophen
rs553050853	Metabolism/PK	3	morphine
rs553050853	Metabolism/PK	3	tapentadol
rs553050853	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs750575779	Metabolism/PK	3	acetaminophen
rs750575779	Metabolism/PK	3	tapentadol
rs750575779	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs751527244	Metabolism/PK	3	acetaminophen
rs751527244	Metabolism/PK	3	morphine
rs751527244	Metabolism/PK	3	tapentadol
rs751527244	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs757573592	Metabolism/PK	3	tapentadol
rs757573592	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs757573592	Metabolism/PK	3	acetaminophen
rs757573592	Metabolism/PK	3	morphine
rs762151655	Metabolism/PK	3	acetaminophen
rs762151655	Metabolism/PK	3	morphine
rs762151655	Metabolism/PK	3	tapentadol
rs762151655	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs767263838	Metabolism/PK	3	acetaminophen
rs767263838	Metabolism/PK	3	morphine
rs767263838	Metabolism/PK	3	tapentadol
rs767263838	Metabolism/PK	3	o-desmethyltramadol;tramadol
rs776817009	Metabolism/PK	3	acetaminophen
rs776817009	Metabolism/PK	3	tapentadol
rs776817009	Metabolism/PK	3	o-desmethyltramadol;tramadol

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs776817009	SULT1A3	3	0.00	3	acetaminophen;tapentadol;o-desmethyltramadol;tramadol
rs762151655	SULT1A3	3	0.00	4	acetaminophen;morphine;tapentadol;o-desmethyltramadol;tramadol
rs750575779	SULT1A3	3	0.00	3	acetaminophen;tapentadol;o-desmethyltramadol;tramadol
rs553050853	SULT1A3	3	0.00	4	acetaminophen;morphine;tapentadol;o-desmethyltramadol;tramadol
rs751527244	SULT1A3	3	0.00	4	acetaminophen;morphine;tapentadol;o-desmethyltramadol;tramadol
rs1293732453	SULT1A3	3	0.00	4	acetaminophen;morphine;tapentadol;o-desmethyltramadol;tramadol
rs1328799050	SULT1A3	3	0.00	4	acetaminophen;morphine;tapentadol;o-desmethyltramadol;tramadol

CTD chemical–gene interactions

83 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dopamine	increases metabolic processing, decreases reaction, increases sulfation	7
2,6-dichloro-4-nitrophenol	decreases sulfation, decreases reaction, increases sulfation, decreases activity, decreases response to substance (+1 more)	4
Estrone	affects cotreatment, decreases sulfation, increases metabolic processing, affects sulfation	3
4-nitrophenol	increases sulfation, increases metabolic processing	2
1-hydroxypyrene	decreases reaction, increases sulfation, increases reaction, increases metabolic processing, decreases activity	2
Benzo(a)pyrene	increases sulfation, increases expression	2
Diethylhexyl Phthalate	affects cotreatment, affects expression, increases expression	2
Estradiol	affects sulfation, increases sulfation	2
Manganese	increases reaction, increases sulfation, decreases expression	2
Sodium Chloride	decreases reaction, increases sulfation	2
harmol	increases sulfation	1
2-hydroxyestradiol	affects sulfation	1
daidzein	decreases reaction, increases sulfation	1
2,4-dichlorophenol	decreases activity	1
naringenin	increases sulfation	1
nitrofen	increases activity	1
nuciferine	increases abundance, increases metabolic processing	1
senecionine	increases expression	1
2,4,5-trichlorophenol	decreases activity	1
6-hydroxymelatonin	increases sulfation	1
N-hydroxy-4-aminobiphenyl	increases sulfation	1
beta-lapachone	increases expression	1
pinocembrin	increases sulfation	1
sodium arsenite	affects binding, increases reaction	1
2,4,6-trichlorophenol	decreases activity	1
5-hydroxyindole	increases sulfation	1
1-naphthol	increases sulfation	1
3,3’-diiodothyronine	decreases reaction, increases sulfation	1
2-chlorophenol	decreases activity	1
2,3,4,6-tetrachlorophenol	decreases activity	1

ChEMBL screening assays

3 unique, capped per target: 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743305	ADMET	Major substrate of human cytosolic sulfotransferase SULT1A3	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2GX	V79-hSULT1A3	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.