TSTD1

Summary

TSTD1 (thiosulfate sulfurtransferase like domain containing 1, HGNC:35410) is a protein-coding gene on chromosome 1q23.3, encoding Thiosulfate:glutathione sulfurtransferase (Q8NFU3). Thiosulfate:glutathione sulfurtransferase (TST) required to produce S-sulfanylglutathione (GSS(-)), a central intermediate in hydrogen sulfide metabolism.

Predicted to enable thiosulfate-thiol sulfurtransferase activity. Predicted to be involved in sulfide oxidation, using sulfide:quinone oxidoreductase. Located in cytoplasmic ribonucleoprotein granule and cytosol.

Source: NCBI Gene 100131187 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_001113207

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35410
Approved symbol	TSTD1
Name	thiosulfate sulfurtransferase like domain containing 1
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KAT
Ensembl gene	ENSG00000215845
Ensembl biotype	protein_coding
OMIM	616041
Entrez	100131187

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000318289, ENST00000368023, ENST00000368024, ENST00000423014, ENST00000462952, ENST00000466967, ENST00000486084, ENST00000939090

RefSeq mRNA: 3 — MANE Select: NM_001113207 NM_001113205, NM_001113206, NM_001113207

CCDS: CCDS44257, CCDS44258, CCDS53400

Canonical transcript exons

ENST00000423014 — 4 exons

Exon	Start	End
ENSE00001040896	161038551	161038673
ENSE00001446152	161038880	161038964
ENSE00003511567	161037631	161037826
ENSE00003611469	161037913	161038075

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0518 / max 255.7475, expressed in 1339 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15563	23.0518	1339

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.15	gold quality
right uterine tube	UBERON:0001302	98.65	gold quality
ileal mucosa	UBERON:0000331	98.58	gold quality
right lobe of thyroid gland	UBERON:0001119	98.57	gold quality
left lobe of thyroid gland	UBERON:0001120	98.49	gold quality
mucosa of transverse colon	UBERON:0004991	98.43	gold quality
kidney epithelium	UBERON:0004819	98.37	gold quality
upper arm skin	UBERON:0004263	98.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.32	gold quality
thyroid gland	UBERON:0002046	98.30	gold quality
renal medulla	UBERON:0000362	97.97	gold quality
bronchial epithelial cell	CL:0002328	97.94	gold quality
pituitary gland	UBERON:0000007	97.94	gold quality
bronchus	UBERON:0002185	97.91	gold quality
adenohypophysis	UBERON:0002196	97.88	gold quality
trachea	UBERON:0003126	97.63	gold quality
lower esophagus mucosa	UBERON:0035834	97.34	gold quality
saliva-secreting gland	UBERON:0001044	97.25	gold quality
body of pancreas	UBERON:0001150	96.86	gold quality
adult mammalian kidney	UBERON:0000082	96.80	gold quality
minor salivary gland	UBERON:0001830	96.80	gold quality
palpebral conjunctiva	UBERON:0001812	96.69	gold quality
superior surface of tongue	UBERON:0007371	96.60	gold quality
mouth mucosa	UBERON:0003729	96.51	gold quality
corpus epididymis	UBERON:0004359	96.34	gold quality
nasal cavity mucosa	UBERON:0001826	96.18	gold quality
prostate gland	UBERON:0002367	96.13	gold quality
esophagus mucosa	UBERON:0002469	96.13	gold quality
pancreatic ductal cell	CL:0002079	96.05	silver quality
right coronary artery	UBERON:0001625	95.97	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	965.37
E-MTAB-10287	yes	48.50
E-GEOD-134144	yes	35.00
E-HCAD-10	yes	31.39
E-HCAD-1	yes	26.04
E-HCAD-11	yes	20.65
E-HCAD-4	yes	18.18
E-HCAD-9	yes	8.52
E-MTAB-8271	yes	7.63
E-MTAB-7303	no	2373.27
E-MTAB-6524	no	224.47
E-CURD-112	no	3.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting TSTD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675

Literature-anchored findings (GeneRIF, showing 4)

• The presence of kynurenine aminotransferase III in Corpora amylacea in the human retina and optic nerve indicates that this enzyme may be relevant in mechanisms of neurodegeneration leading to Corpora amylaceaformation. (PMID:21845542)
• Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog. (PMID:24981631)
• Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder. (PMID:27030575)
• Data suggest that TSTD1 can utilize thioredoxin as an acceptor in the presence of thioredoxin reductase and NADPH. (PMID:29348167)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tstd1	ENSDARG00000071567
mus_musculus	Tstd1	ENSMUSG00000103711
rattus_norvegicus		ENSRNOG00000076904

Paralogs (1): CEP41 (ENSG00000106477)

Protein

Protein identifiers

Thiosulfate:glutathione sulfurtransferase — Q8NFU3 (reviewed: Q8NFU3)

All UniProt accessions (2): Q8NFU3, R4GNF9

UniProt curated annotations — full annotation on UniProt →

Function. Thiosulfate:glutathione sulfurtransferase (TST) required to produce S-sulfanylglutathione (GSS(-)), a central intermediate in hydrogen sulfide metabolism. Provides the link between the first step in mammalian H(2)S metabolism performed by the sulfide:quinone oxidoreductase (SQOR) which catalyzes the conversion of H(2)S to thiosulfate, and the sulfur dioxygenase (SDO) which uses GSS(-) as substrate. The thermodynamic coupling of the irreversible SDO and reversible TST reactions provides a model for the physiologically relevant reaction with thiosulfate as the sulfane donor. GSS(-) spontaneously reacts with glutathione to form glutathione disulfide.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. Highly expressed in kidney, liver and skeletal muscle. Lower levels of expression in heart, colon, thymus, spleen, placenta and lung. Weakly expressed in brain, small intestine and peripheral blood leukocytes. Expressed at high levels in the breast carcinoma cell lines MCF-7 and MDA-MB-468 and at a lower level in the breast carcinoma cell line MDA-MB-231, the colon carcinoma call line LoVo and the lung carcinoma cell line A-549. No expression in the cell lines EFO-27 and HeLa, or the normal breast tissue cell lines MCF-10A and H184A1. Detected in invasive ductal carcinoma, but not in the adjacent tissues.

Activity regulation. GSS(-) is a potent inhibitor of TSTD1, since the presence of the sulfur dioxygenase (SDO) strongly increases the TSTD1 catalytic activity.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NFU3-1	1	yes
Q8NFU3-2	2
Q8NFU3-3	3
Q8NFU3-4	4

RefSeq proteins (3): NP_001106676, NP_001106677, NP_001106678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001763	Rhodanese-like_dom	Domain
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily
IPR042457	TSTD1_mml	Family

Pfam: PF00581

Enzyme classification (BRENDA):

• EC 2.8.1.1 — thiosulfate sulfurtransferase (BRENDA: 45 organisms, 64 substrates, 66 inhibitors, 78 Km, 10 kcat entries)
• EC 2.8.1.3 — thiosulfate-thiol sulfurtransferase (BRENDA: 3 organisms, 9 substrates, 10 inhibitors, 8 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
THIOSULFATE	0.53–603	45
CN-	0.03–27	19
CYANIDE	0.27–14	6
3-MERCAPTOPYRUVATE	3.7–51.7	3
GLUTATHIONE	0.89–11	3
THIOSULFATE	2.9–17	3
THIOREDOXIN	0.017–0.034	2
H2S	8.8	1
POLYSULFIDE	0.05	1
TETRATHIONATE	6.9	1
BENZENETHIOSULFONATE	0.24	1
CYANIDE	3	1

Catalyzed reactions (Rhea), 2 shown:

• thiosulfate + 2 glutathione = glutathione disulfide + hydrogen sulfide + sulfite + 2 H(+) (RHEA:14505)
• thiosulfate + glutathione = S-sulfanylglutathione + sulfite + H(+) (RHEA:55976)

UniProt features (17 total): helix 6, strand 4, splice variant 3, chain 1, domain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6BEV	X-RAY DIFFRACTION	1.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFU3-F1	94.06	0.93

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): 79 (cysteine persulfide intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
79	leads to the loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1614517	Sulfide oxidation to sulfate

MSigDB gene sets: 86 (showing top): CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GARY_CD5_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_LIVER_METABOLISM_QTL_CIS, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_SULPHUR_CONTAINING_GROUPS, LEE_DIFFERENTIATING_T_LYMPHOCYTE, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, GOMF_SULFURTRANSFERASE_ACTIVITY, REACTOME_SULFIDE_OXIDATION_TO_SULFATE, REACTOME_DEGRADATION_OF_CYSTEINE_AND_HOMOCYSTEINE, HDAC4_TARGET_GENES, ZNF362_TARGET_GENES, MIR22_5P, MIR2116_5P

GO Biological Process (1): obsolete sulfide oxidation, using sulfide:quinone oxidoreductase (GO:0070221)

GO Molecular Function (2): thiosulfate-thiol sulfurtransferase activity (GO:0050337), transferase activity (GO:0016740)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic ribonucleoprotein granule (GO:0036464), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Degradation of cysteine and homocysteine	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
sulfurtransferase activity	1
catalytic activity	1
intracellular anatomical structure	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

1625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSTD1	TST	Q16762	655
TSTD1	SQOR	Q9Y6N5	508
TSTD1	SUOX	P51687	493
TSTD1	ETHE1	O95571	486
TSTD1	KIAA1143	Q96AT1	461
TSTD1	MPST	P25325	443
TSTD1	CTH	P32929	433
TSTD1	NRN1L	Q496H8	428
TSTD1	TBC1D23	Q9NUY8	419
TSTD1	IZUMO4	Q1ZYL8	400
TSTD1	PAPSS1	O43252	380
TSTD1	SDR42E1	Q8WUS8	369
TSTD1	TRMU	O75648	350
TSTD1	FLAD1	Q8NFF5	349
TSTD1	MOCS1	Q9NZB8	349
TSTD1	MOCS2	O96007	349
TSTD1	CCS	O14618	349

IntAct

0 interactions, top by confidence:

BioGRID (1): TSTD1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A6QLU8, O46607, O70325, P00435, P04041, P07203, P07850, P11352, P11909, P18283, P21765, P22352, P23764, P28714, P36968, P36969, P36970, P37141, P46412, P83645, P97346, Q0EF98, Q0EF99, Q0EFA0, Q32QL6, Q4AEG9, Q4AEH0, Q4AEH1, Q4AEH2, Q4AEH3, Q4AEH4, Q4AEH5, Q4AEH7, Q4AEH8, Q4AEH9, Q4AEI0, Q4AEI1, Q4AEI2

Diamond homologs: H0UI37, P22978, Q8NFU3, Q9D0B5, Q08742, Q12305, Q9ZNW0, A0KEH8, A4TGR3, A4WFK9, A4XZJ7, A5VXJ2, A6TF44, A6UZ93, A7FNW5, A8GKU1, A9MMA6, A9MTU1, A9R4D5, B1JE10, B1JHY9, B2K5W3, B4EZM9, B4SVM2, B4TKV1, B4TY78, B5BHH6, B5FCB8, B5FKE4, B5R384, B5XTR4, B6ENU6, B7V4H5, B8F6J5, B9DJ55, O08446, P0AG27, P0AG28, P0AG29, P23857

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

705 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161037994:T:C	donor_gain	1.0000
1:161038881:T:TA	donor_gain	1.0000
1:161037769:T:TA	donor_gain	0.9900
1:161037911:AC:A	donor_gain	0.9900
1:161037912:CC:C	donor_gain	0.9900
1:161037963:G:A	donor_gain	0.9900
1:161037993:ATCTT:A	donor_gain	0.9900
1:161037997:T:TA	donor_gain	0.9900
1:161038074:CA:C	acceptor_gain	0.9900
1:161038076:C:CC	acceptor_gain	0.9900
1:161038084:G:GC	acceptor_gain	0.9900
1:161038093:G:C	acceptor_gain	0.9900
1:161038567:C:A	donor_gain	0.9900
1:161038875:GGTA:G	donor_loss	0.9900
1:161038876:GTAC:G	donor_loss	0.9900
1:161038877:TACCT:T	donor_loss	0.9900
1:161038878:AC:A	donor_loss	0.9900
1:161038879:C:CG	donor_loss	0.9900
1:161037825:CC:C	acceptor_gain	0.9800
1:161037826:CC:C	acceptor_gain	0.9800
1:161037905:C:A	donor_gain	0.9800
1:161037968:T:C	donor_gain	0.9800
1:161038072:GACA:G	acceptor_gain	0.9800
1:161038075:AC:A	acceptor_loss	0.9800
1:161038076:C:CG	acceptor_loss	0.9800
1:161038077:T:C	acceptor_loss	0.9800
1:161038084:G:C	acceptor_gain	0.9800
1:161038592:T:TA	donor_gain	0.9800
1:161038817:C:CA	donor_gain	0.9800
1:161038875:GGTAC:G	donor_loss	0.9800

AlphaMissense

723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161038032:G:C	F59L	0.987
1:161038032:G:T	F59L	0.987
1:161038034:A:G	F59L	0.987
1:161038605:G:T	R27S	0.982
1:161037934:G:T	A92D	0.980
1:161038033:A:G	F59S	0.977
1:161038574:A:G	I37T	0.971
1:161038556:A:G	I43T	0.968
1:161038610:T:A	D25V	0.967
1:161037982:A:T	V76D	0.966
1:161038610:T:C	D25G	0.962
1:161038610:T:G	D25A	0.961
1:161038556:A:C	I43S	0.960
1:161037978:G:C	F77L	0.959
1:161037978:G:T	F77L	0.959
1:161037980:A:G	F77L	0.959
1:161038609:G:C	D25E	0.959
1:161038609:G:T	D25E	0.959
1:161037946:G:T	A88D	0.958
1:161037956:C:G	G85R	0.958
1:161038033:A:C	F59C	0.958
1:161037947:C:G	A88P	0.957
1:161037974:A:G	C79R	0.957
1:161038611:C:G	D25H	0.957
1:161037973:C:T	C79Y	0.955
1:161038556:A:T	I43N	0.952
1:161037979:A:G	F77S	0.951
1:161038604:C:G	R27P	0.951
1:161037795:A:G	W110R	0.950
1:161037795:A:T	W110R	0.950

dbSNP variants (sampled 300 via entrez): RS1000010156 (1:161040145 A>G), RS1000080464 (1:161038710 G>A,T), RS1000550967 (1:161040479 A>G), RS1002068278 (1:161037700 G>A,T), RS1003072486 (1:161038286 G>C), RS1004127617 (1:161039537 G>A), RS1004178674 (1:161039196 A>G), RS1004513386 (1:161038044 C>T), RS1008585995 (1:161038663 G>A,C), RS1008721752 (1:161038438 G>C), RS1010853329 (1:161037333 A>AC), RS1012934227 (1:161040879 A>G), RS1013237007 (1:161038967 T>C,G), RS1014153204 (1:161039808 T>A,C,G), RS1014494183 (1:161037746 G>A,C)

Disease associations

OMIM: gene MIM:616041 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_114	Night sleep phenotypes	7.000000e-06
GCST003542_135	Night sleep phenotypes	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
methylmercuric chloride	decreases expression	3
Estradiol	affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	2
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Berberine	increases expression	1
Diuron	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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