TST

Summary

TST (thiosulfate sulfurtransferase, HGNC:12388) is a protein-coding gene on chromosome 22q12.3, encoding Thiosulfate sulfurtransferase (Q16762). Catalyzes the transfer of sulfur ion from thiosulfate to cyanide, although other thiol compounds, besides cyanide, can act as sulfur ion acceptors.

This is one of two neighboring genes encoding similar proteins that each contain two rhodanese domains. The encoded protein is localized to the mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite. In addition, the protein interacts with 5S ribosomal RNA and facilitates its import into the mitochondria. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7263 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• GTEx eGene: eQTL in 31 tissues, sQTL in 1 (q < 0.05)
• ChEMBL bioactivity: 17 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.48 (unconstrained)
• MANE Select transcript: NM_003312
• Notable: 53 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12388
Approved symbol	TST
Name	thiosulfate sulfurtransferase
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	RDS
Ensembl gene	ENSG00000128311
Ensembl biotype	protein_coding
OMIM	180370
Entrez	7263

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

MANE Select: ENST00000249042

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 5: 1

ENST00000249042, ENST00000403892, ENST00000438203, ENST00000622841, ENST00000864747, ENST00000864748, ENST00000864749, ENST00000864750, ENST00000864751, ENST00000864752, ENST00000864753, ENST00001095808, ENST00001095809, ENST00001109768, ENST00001123203, ENST00001131800

RefSeq mRNA: 2 — MANE Select: NM_003312 NM_001270483, NM_003312

CCDS: CCDS13938

Canonical transcript exons

ENST00000249042 — 3 exons

Exon	Start	End
ENSE00000880104	37018138	37018753
ENSE00001045113	37019400	37019447
ENSE00003844735	37010865	37011325

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2127 / max 278.4387, expressed in 1755 samples.

Highest expression (Bgee): mucosa of transverse colon, colonic mucosa, lobe of liver, mucosa of sigmoid colon, ileal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TST is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Spinal cord cervical c-1	eqtl	1.2e-16	+0.89	22:37022220:G:A
Brain Hippocampus	eqtl	3.8e-14	+0.59	22:37022220:G:A
Thyroid	eqtl	7.0e-14	-0.20	22:37025661:A:G
Skin Sun Exposed Lower leg	eqtl	4.1e-11	+0.18	22:37022220:G:A
Skin Not Sun Exposed Suprapubic	eqtl	6.2e-07	+0.17	22:37022220:G:A
Brain Frontal Cortex BA9	eqtl	2.1e-06	+0.27	22:37022220:G:A
Cells Cultured fibroblasts	eqtl	4.0e-06	+0.20	22:37022220:G:A
Brain Cerebellar Hemisphere	eqtl	5.3e-06	+0.19	22:37013185:G:A
Pancreas	eqtl	1.2e-05	-0.23	22:37012189:A:G
Brain Caudate basal ganglia	eqtl	1.5e-05	+0.27	22:37022220:G:A
Artery Tibial	eqtl	3.7e-05	-0.58	22:37600146:A:G
Brain Cerebellum	eqtl	4.3e-05	+0.20	22:37008208:G:A
Brain Substantia nigra	eqtl	1.1e-04	+0.42	22:37022220:G:A
Brain Cortex	eqtl	1.3e-04	+0.29	22:37022220:G:A
Adrenal Gland	eqtl	2.5e-04	+0.23	22:37009630:C:T
Brain Putamen basal ganglia	eqtl	3.8e-04	+0.19	22:37007261:C:T
Brain Anterior cingulate cortex BA24	eqtl	5.3e-04	+0.20	22:36984976:A:G
Heart Left Ventricle	eqtl	7.4e-04	-0.13	22:37017628:A:ACAGACGG
Esophagus Mucosa	eqtl	1.4e-03	+0.15	22:37022220:G:A
Cells EBV-transformed lymphocytes	eqtl	2.0e-03	+0.73	22:37018427:T:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193987	17.2127	1755

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.54	gold quality
colonic mucosa	UBERON:0000317	99.21	gold quality
right lobe of liver	UBERON:0001114	99.11	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.10	gold quality
ileal mucosa	UBERON:0000331	98.82	gold quality
right adrenal gland cortex	UBERON:0035827	98.59	gold quality
liver	UBERON:0002107	98.56	gold quality
right adrenal gland	UBERON:0001233	98.49	gold quality
jejunal mucosa	UBERON:0000399	98.02	gold quality
duodenum	UBERON:0002114	97.99	gold quality
left adrenal gland	UBERON:0001234	97.91	gold quality
left adrenal gland cortex	UBERON:0035825	97.87	gold quality
nephron tubule	UBERON:0001231	97.82	gold quality
adrenal cortex	UBERON:0001235	97.69	gold quality
lower esophagus mucosa	UBERON:0035834	97.53	gold quality
esophagus squamous epithelium	UBERON:0006920	96.91	gold quality
kidney epithelium	UBERON:0004819	96.90	gold quality
renal glomerulus	UBERON:0000074	96.62	gold quality
pancreatic ductal cell	CL:0002079	96.55	gold quality
metanephric glomerulus	UBERON:0004736	96.46	gold quality
transverse colon	UBERON:0001157	96.37	gold quality
rectum	UBERON:0001052	96.01	gold quality
epithelium of esophagus	UBERON:0001976	95.97	gold quality
gingival epithelium	UBERON:0001949	95.92	gold quality
adult mammalian kidney	UBERON:0000082	95.91	gold quality
adrenal gland	UBERON:0002369	95.86	gold quality
esophagus mucosa	UBERON:0002469	95.69	gold quality
squamous epithelium	UBERON:0006914	95.57	gold quality
gall bladder	UBERON:0002110	95.46	gold quality
body of stomach	UBERON:0001161	94.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.30	gold quality
pharyngeal mucosa	UBERON:0000355	94.26	gold quality
amniotic fluid	UBERON:0000173	94.21	gold quality
small intestine	UBERON:0002108	94.20	gold quality
heart left ventricle	UBERON:0002084	94.14	gold quality
gingiva	UBERON:0001828	94.08	gold quality
cardiac ventricle	UBERON:0002082	93.97	gold quality
cortex of kidney	UBERON:0001225	93.74	gold quality
kidney	UBERON:0002113	93.66	gold quality
cervix squamous epithelium	UBERON:0006922	93.43	gold quality
cranial nerve II	UBERON:0000941	93.30	gold quality
jejunum	UBERON:0002115	93.29	gold quality
body of pancreas	UBERON:0001150	93.27	gold quality
large intestine	UBERON:0000059	93.20	gold quality
intestine	UBERON:0000160	93.16	gold quality
metanephros	UBERON:0000081	93.08	gold quality
colon	UBERON:0001155	93.00	gold quality
apex of heart	UBERON:0002098	92.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.68	gold quality
heart right ventricle	UBERON:0002080	92.58	gold quality
palpebral conjunctiva	UBERON:0001812	92.54	gold quality
cervix epithelium	UBERON:0004801	92.51	gold quality
parotid gland	UBERON:0001831	92.46	gold quality
stomach	UBERON:0000945	92.26	gold quality
gastrocnemius	UBERON:0001388	92.23	gold quality
right atrium auricular region	UBERON:0006631	91.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.86	gold quality
omental fat pad	UBERON:0010414	91.85	gold quality
peritoneum	UBERON:0002358	91.82	gold quality
parietal pleura	UBERON:0002400	91.63	gold quality
mammalian vulva	UBERON:0000997	91.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.59	gold quality
oral cavity	UBERON:0000167	91.57	gold quality
esophagus	UBERON:0001043	91.55	gold quality
heart	UBERON:0000948	91.48	gold quality
cardiac atrium	UBERON:0002081	90.97	gold quality
muscle of leg	UBERON:0001383	90.65	gold quality
fundus of stomach	UBERON:0001160	90.64	gold quality
vagina	UBERON:0000996	90.62	gold quality
body of tongue	UBERON:0011876	90.61	gold quality
adipose tissue	UBERON:0001013	90.50	gold quality
pylorus	UBERON:0001166	90.50	gold quality
germinal epithelium of ovary	UBERON:0001304	90.50	gold quality
eye	UBERON:0000970	90.43	gold quality
caudate nucleus	UBERON:0001873	90.20	gold quality
biceps brachii	UBERON:0001507	90.15	gold quality
epithelium of bronchus	UBERON:0002031	90.13	gold quality
putamen	UBERON:0001874	90.10	gold quality
bronchus	UBERON:0002185	89.83	gold quality
adult organism	UBERON:0007023	89.69	gold quality
substantia nigra	UBERON:0002038	89.66	gold quality
muscle organ	UBERON:0001630	89.61	gold quality
endometrium epithelium	UBERON:0004811	89.58	gold quality
connective tissue	UBERON:0002384	89.56	gold quality
bronchial epithelial cell	CL:0002328	89.52	gold quality
tongue squamous epithelium	UBERON:0006919	89.49	gold quality
triceps brachii	UBERON:0001509	89.37	gold quality
pleura	UBERON:0000977	89.35	gold quality
right ovary	UBERON:0002118	89.35	gold quality
sigmoid colon	UBERON:0001159	89.26	gold quality
lateral globus pallidus	UBERON:0002476	89.25	gold quality
right uterine tube	UBERON:0001302	89.20	gold quality
gluteal muscle	UBERON:0002000	89.09	gold quality
metanephros cortex	UBERON:0010533	89.02	gold quality
saliva-secreting gland	UBERON:0001044	89.01	gold quality
mouth mucosa	UBERON:0003729	88.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.94	gold quality
deltoid	UBERON:0001476	88.89	gold quality
amygdala	UBERON:0001876	88.89	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	16.22
E-MTAB-8410	yes	15.43
E-MTAB-7303	no	548.99
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	240.4	high
Spinal cord	tissue	170.7
Colon	tissue	141.0	high
Duodenum	tissue	138.9	high
Medulla oblongata	tissue	125.4
Midbrain	tissue	117.2
Small intestine	tissue	107.6	high
Periaqueductal gray	tissue	106.6
Substantia nigra	tissue	104.7
Pons	tissue	102.7
Hypothalamus	tissue	93.6
Thalamus	tissue	93.2
Stomach 1	tissue	83.4	high
Rectum	tissue	75.4	high
Superior colliculi	tissue	73.4
Gallbladder	tissue	71.3	high
Frontal cortex	tissue	65.4
Kidney	tissue	61.5	high
Adrenal gland	tissue	58.6	high
Vagina	tissue	55.0	medium
Caudate putamen	tissue	52.9
Septum	tissue	49.3
Hippocampal formation	tissue	48.2
Amygdala	tissue	47.5
Esophagus	tissue	45.9	low
Putamen	tissue	44.4
Corpus callosum	tissue	43.7
Pancreas	tissue	43.0	medium
Ventral forebrain	tissue	37.7
Salivary gland	tissue	37.5	medium
Adipose tissue	tissue	34.7	medium
Tongue	tissue	32.5
Cervix	tissue	32.1	high
Cerebral cortex	tissue	31.6	medium
Retrosplenial cortex	tissue	31.6
Skeletal muscle	tissue	31.0	low
Motor cortex	tissue	30.4
Basal ganglia	tissue	29.3	medium
Somatosensory cortex	tissue	29.0
Entorhinal cortex	tissue	28.5
Temporal cortex	tissue	28.5
Insular cortex	tissue	27.4
Heart muscle	tissue	27.2	low
Olfactory bulb	tissue	27.0
Retrosplenial and cingulate cortex	tissue	26.8
Prefrontal cortex	tissue	26.3
Occipital cortex	tissue	26.2
Cerebellum	tissue	25.6	medium
Bone marrow	tissue	25.5	low
Ovary	tissue	25.3	medium
Choroid plexus	tissue	24.8
Fallopian tube	tissue	24.1	high
Nucleus accumbens	tissue	22.8
Locus coeruleus	tissue	21.2
Hippocampus	tissue	19.8	low
Appendix	tissue	19.8	high
Urinary bladder	tissue	18.7	high
Lung	tissue	18.4	medium
Seminal vesicle	tissue	17.2	low
Tonsil	tissue	15.2	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (170.7), Dorsal spinal cord (120.0), Ventral hippocampus (48.2), Subiculum (46.0), Dorsal hippocampus (45.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

Targeting TST by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-6850-3P	88.96	69.27	33

Functional genomics

gnomAD constraint: pLI 1.24e-09, LOEUF 1.48, missense Z 0.156 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000249042 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 7)

• The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. (PMID:17035239)
• Proteomics was used to study colonic epithelial aging, for differential proteins in the human normal colonic epithelial tissues from young and old people. Rack1, EF-Tu and Rhodanese, three validated differential proteins, were further investigated. (PMID:20099848)
• silencing of the rhodanese gene caused not only a proportional decrease of 5 S rRNA import but also a general inhibition of mitochondrial translation, indicating the functional importance of the imported 5 S rRNA inside the organelle. (PMID:20663881)
• Loss of Thiosulfate Sulfurtransferase is associated with decreased mucosal sulfide detoxification capacity in patients with Crohn’s disease (PMID:23399736)
• show that polymorphic variations that are distant from the active site differentially modulate the sulfurtransferase activity of human rhodanese to cyanide versus sulfite (PMID:26269602)
• TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. (PMID:27270587)
• Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases. (PMID:32061776)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpst	ENSDARG00000093235
mus_musculus	Tst	ENSMUSG00000044986
rattus_norvegicus	Tst	ENSRNOG00000000186
caenorhabditis_elegans		WBGENE00008409
caenorhabditis_elegans		WBGENE00010380
caenorhabditis_elegans		WBGENE00010383
caenorhabditis_elegans		WBGENE00011307
caenorhabditis_elegans		WBGENE00017387
caenorhabditis_elegans		WBGENE00022006
caenorhabditis_elegans		WBGENE00022007

Paralogs (1): MPST (ENSG00000128309)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98852) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased leukocyte cell number	1
abnormal testis morphology	1
small testis	1
increased mean corpuscular volume	1
abnormal epididymis morphology	1
enlarged epididymis	1
increased lymphocyte cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis variant bovis AF2122/97	P59989	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WHF8	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WHF9	100.0%	Diamond
Escherichia coli K-12	P31142	99.6%	Diamond
Escherichia coli O157:H7	P58388	99.6%	Diamond
Cricetulus griseus	P46635	95.6%	Diamond
Bos taurus	P00586	91.9%	Diamond
Arabidopsis thaliana	O64530	78.5%	Diamond
Gallus gallus	P25324	72.8%	Diamond
Thermus thermophilus HB27	Q72JV2	64.5%	Diamond
Deinococcus radiodurans R1 = ATCC 13939 = DSM 20539	Q9RXT9	64.5%	Diamond
Corynebacterium glutamicum ATCC 13032	P71121	60.3%	Diamond
Haloferax volcanii DS2	D4GYM0	54.8%	Diamond
Pseudomonas aeruginosa PAO1	Q9I452	42.8%	Diamond
Schizosaccharomyces pombe 972h-	Q9USJ1	41.0%	Diamond
Saccharomyces cerevisiae S288C	Q08686	36.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CIMIP4	protein-coding	339669
MPST	protein-coding	4357
IL2RB-AS1	ncRNA	139281655
TMPRSS6	protein-coding	164656
IL2RB	protein-coding	3560
KCTD17	protein-coding	79734
LL22NC01-81G9.3	ncRNA	100506241

Protein

Protein identifiers

Thiosulfate sulfurtransferase — Q16762 (reviewed: Q16762)

Alternative names: Rhodanese

All UniProt accessions (3): A0A384NKQ2, B1AH48, Q16762

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of sulfur ion from thiosulfate to cyanide, although other thiol compounds, besides cyanide, can act as sulfur ion acceptors. It also has weak mercaptopyruvate sulfurtransferase (MST) activity. Has a pivotal role in cyanide detoxification. Together with MRPL18, acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion. Mitochondrion matrix.

Domain organisation. Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue.

RefSeq proteins (2): NP_001257412, NP_003303* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001307	Thiosulphate_STrfase_CS	Conserved_site
IPR001763	Rhodanese-like_dom	Domain
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily
IPR045078	TST/MPST-like	Family

Pfam: PF00581

Catalyzed reactions (Rhea)

• thiosulfate + hydrogen cyanide = thiocyanate + sulfite + 2 H(+) (RHEA:16881)

UniProt features (51 total): helix 14, modified residue 13, strand 10, turn 3, domain 2, sequence variant 2, binding site 2, initiator methionine 1, chain 1, glycosylation site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8AGF	Crystal structure of human Thiosulfate sulfurtransferase amino acids 2-297	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16762-F1	96.50	0.96

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
248	cysteine persulfide intermediate

Ligand- & substrate-binding residues (2)

Position	Role
187	substrate
250	substrate

Post-translational modifications (13)

Type	Positions
Phosphoserine	38
N6-acetyllysine	136, 163, 175, 224, 236, 237, 14
N6-succinyllysine	136, 175, 224, 237, 14

Glycosylation sites (1)

Type	Positions
O-linked (glcnac) serine	35

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-1614558	Degradation of cysteine and homocysteine	curated
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-1614517	Sulfide oxidation to sulfate	electronic
R-HSA-1614635	Sulfur amino acid metabolism	—

MSigDB gene sets: 224 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, GNF2_GSTM1, ENK_UV_RESPONSE_KERATINOCYTE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, SMITH_TERT_TARGETS_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, MODULE_285

GO Biological Process (5): sulfur amino acid catabolic process (GO:0000098), cyanate catabolic process (GO:0009440), epithelial cell differentiation (GO:0030855), rRNA import into mitochondrion (GO:0035928), rRNA transport (GO:0051029)

GO Molecular Function (5): thiosulfate-cyanide sulfurtransferase activity (GO:0004792), 5S rRNA binding (GO:0008097), sulfurtransferase activity (GO:0016783), RNA binding (GO:0003723), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Degradation of cysteine and homocysteine	1
Sulfur amino acid metabolism	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

18 GO namespaces:

Category	Terms
sulfur amino acid metabolic process	1
sulfur compound catabolic process	1
carboxylic acid catabolic process	1
catabolic process	1
cell differentiation	1
epithelium development	1
RNA import into mitochondrion	1
rRNA transport	1
RNA transport	1
sulfurtransferase activity	1
rRNA binding	1
transferase activity, transferring sulphur-containing groups	1
nucleic acid binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
epithelial cell differentiation	BP	direct assay
rRNA import into mitochondrion	BP	mutant phenotype
rRNA transport	BP	direct assay
mitochondrion	CC	direct assay
5S rRNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 897 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TST	MOCS3	O95396	926
TST	NFS1	Q9Y697	829
TST	HSPD1	P10809	816
TST	SUOX	P51687	816
TST	ETHE1	O95571	806
TST	CTH	P32929	788
TST	SQOR	Q9Y6N5	779
TST	P0DN79	P0DN79	675
TST	H7C2H4	H7C2H4	674
TST	HSPE1	P61604	671
TST	URM1	Q9BTM9	663
TST	MOCS2	O96007	662
TST	ISCU	Q9H1K1	657
TST	LYRM4	Q9HD34	622
TST	HSPA9	P30036	613

IntAct

Human interaction partners of TST in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PNMA2	physical association	0.400	1

BioGRID (79 interactions; top human partners by supporting records): CLPP (Proximity Label-MS; 3 records), FAHD2A (Co-fractionation; 2 records), LYPLAL1 (Co-fractionation; 2 records), PEBP1 (Co-fractionation; 2 records), AASS (Cross-Linking-MS (XL-MS)), ABAT (Co-fractionation), ACOT1 (Co-fractionation), AIFM1 (Co-fractionation), AKR1C2 (Co-fractionation), ALDH4A1 (Co-fractionation), AMHR2 (Negative Genetic), ANXA11 (Co-fractionation), BPHL (Co-fractionation), C19orf10 (Co-fractionation), CLIC1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TST: 53 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 176):

Position(s)	Effect	Δscore	Sites
22:37018136–37018137	donor_loss	1.0000	3
22:37011326–37011327	acceptor_loss	0.9900	6
22:37018136–37018137	donor_loss	0.9900	2
22:37018772	acceptor_gain	0.9900
22:37018771	acceptor_gain	0.9800
22:37019334	donor_gain	0.9800
22:37019402	donor_gain	0.9800
22:37011337	acceptor_loss	0.9700
22:37018761	acceptor_gain	0.9500
22:37011332	acceptor_gain	0.9400

AlphaMissense

687 missense substitutions predicted likely pathogenic (of 1,908 scored), across 183 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D181	8	0.984	0.993
D33	8	0.962	0.978
F81	8	0.954	0.991
D273	8	0.948	0.975
F116	8	0.920	0.980
F59	8	0.916	0.980
F233	8	0.889	0.972
D100	8	0.885	0.956
N171	8	0.780	0.955
H95	8	0.699	0.834
W276	7	0.977	0.992
R183	7	0.975	0.997
W134	7	0.971	0.992
F153	7	0.969	0.989
W113	7	0.959	0.991
F188	7	0.958	0.992
W279	7	0.955	0.992
W114	7	0.947	0.992
F119	7	0.946	0.981
H52	7	0.942	0.992

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.00019
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000723

Disease associations

OMIM: gene MIM:180370 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST003044_87	Crohn’s disease	9e-9
GCST003043_35	Inflammatory bowel disease	1e-8

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295835 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 919,004 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

17 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1536	ERGOCALCIFEROL	4	35,935
CHEMBL1200712	EVANS BLUE	4	24,401
CHEMBL64894	GENTIAN VIOLET	4	112,306
CHEMBL496	HEXACHLOROPHENE	4	26,440
CHEMBL590	MENADIONE	4	21,230
CHEMBL704	MESALAMINE	4	53,080
CHEMBL550495	METHYLENE BLUE	4	591
CHEMBL506	PRIMAQUINE	4	10,353
CHEMBL1534	RIBOFLAVIN	4	137,559
CHEMBL3989697	RIBOFLAVIN 5’-PHOSPHATE SODIUM	4	61
CHEMBL506247	TANNIC ACID	4	27,154
CHEMBL38	TRETINOIN	4	195,980
CHEMBL140	CURCUMIN	3	95,185
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	23,201
CHEMBL284328	HOMIDIUM BROMIDE	2	148,557
CHEMBL15192	LAPACHONE	2	606
CHEMBL295316	PLUMBAGIN	1	6,365

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

75 measured of 131 human assays (136 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol	EC50	1.5 nM
Azovan Blue	IC50	170 nM
CHEMBL4161583	IC50	1000 nM
Tash 1	IC50	1200 nM
SMR000058356	IC50	1300 nM
CHEMBL5653589	KD	1440 nM
CHEMBL4167333	IC50	2100 nM
R115 (Reactive Blue 2)	IC50	2100 nM
2,7-diamino-10-ethyl-9-phenylphenanthridinium bromide	IC50	2160 nM
CHEBI:3962	IC50	2300 nM
6-(3-adamantan-1-yl-4-methoxyphenyl)naphthalene-2-carboxylic acid	IC50	2300 nM
CHEMBL4169499	IC50	2400 nM
cid_2406	IC50	2800 nM
Rafoxanide	IC50	2800 nM
ERYTHROSINE SODIUM	IC50	2900 nM
Ascorbyl Palmitate	IC50	3100 nM
MLS002153482	IC50	3200 nM
US8987474, Hematin	IC50	3600 nM	US-8987474: Inhibition of Shp2/PTPN11 protein tyrosine phosphatase by NSC-87877, NSC-117199 and their analogs
CHEMBL1632145	IC50	3600 nM
cid_16129778	IC50	3800 nM
[1-14C]Arachidonic acid	IC50	4500 nM
CHEMBL4160098	IC50	4500 nM
CHEMBL4166077	IC50	4700 nM
CHEMBL4277733	IC50	4700 nM
CHEBI:15430	IC50	4900 nM
CHEMBL4176697	IC50	5000 nM
ALL-TRANS-RETINOIC ACID	IC50	5300 nM
CHEBI:77181	IC50	5800 nM
CHEMBL4162794	IC50	5900 nM
CETYLPYRIDINIUM BROMIDE	IC50	6000 nM
CHEMBL4161487	IC50	6100 nM
plumbagin	IC50	6300 nM
CHEMBL4448756	IC50	6800 nM
CHEMBL4293874	IC50	6900 nM
MLS001333620	IC50	7400 nM
cid_2333	IC50	9100 nM
4-NONYLPHENOL	IC50	9500 nM
Closantel	IC50	10000 nM
5beta-cholanic acid-3alpha-ol	IC50	10000 nM
CHEBI:28940	IC50	11000 nM
CHEMBL3040216	IC50	11000 nM
CHEMBL4168023	IC50	11000 nM
Thiostrepton 1	IC50	13000 nM
CHEBI:29534	IC50	15000 nM
1-(4-methoxyphenyl)-3-phenylprop-2-en-1-one (6)	IC50	16000 nM
ABAMECTIN	IC50	16000 nM
4-chloro-2-(5-chloro-2-hydroxybenzyl)phenol	IC50	17000 nM
CHEMBL1879202	IC50	17000 nM
[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid	IC50	18300 nM
(E)-1-(4-Hydroxy-phenyl)-3-phenyl-propenone	IC50	20000 nM

ChEMBL bioactivities

18 potent at pChembl≥5 of 31 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Kd	39.84	nM	CHEMBL5653589
7.40	ED50	39.84	nM	CHEMBL5653589
7.22	IC50	60	nM	PLUMBAGIN
6.92	IC50	120	nM	LAPACHONE
6.55	IC50	280	nM	MESALAMINE
6.48	IC50	330	nM	GOSSYPETIN
6.42	IC50	380	nM	RIBOFLAVIN 5’-PHOSPHATE SODIUM
6.08	IC50	830	nM	HOMIDIUM BROMIDE
6.00	IC50	1000	nM	MENADIONE
5.64	IC50	2300	nM	PURPURIN
5.54	IC50	2900	nM	PRIMAQUINE
5.21	IC50	6100	nM	METHYLENE BLUE
5.14	IC50	7300	nM	EPIGALOCATECHIN GALLATE
5.07	IC50	8500	nM	CHEMBL4448756
5.06	IC50	8800	nM	RIBOFLAVIN
5.06	IC50	8700	nM	EVANS BLUE
5.04	IC50	9200	nM	CHEMBL5483017
5.01	IC50	9700	nM	HARMALOL

PubChem BioAssay actives

17 with measured affinity, of 144 total; 17 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149666: Binding affinity to human TST incubated for 45 mins by Kinobead based pull down assay	kd	0.0398	uM
5-hydroxy-2-methylnaphthalene-1,4-dione	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.0600	uM
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.1200	uM
mesalamine	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.2800	uM
2-(3,4-dihydroxyphenyl)-3,5,7,8-tetrahydroxychromen-4-one	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.3300	uM
riboflavin 5’-phosphate sodium anhydrous	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.3800	uM
5-ethyl-6-phenylphenanthridin-5-ium-3,8-diamine bromide	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	0.8300	uM
Menadione	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	1.0000	uM
1,2,4-trihydroxyanthracene-9,10-dione	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	2.3000	uM
Primaquine	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	2.9000	uM
[7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	6.1000	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	7.3000	uM
tetrasodium;4-amino-6-[[4-[4-[[8-amino-5,7-bis[dihydroxy(oxido)-lambda4-sulfanyl]-1-hydroxynaphthalen-2-yl]diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonate	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	8.5000	uM
tetrasodium;4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonate	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	8.7000	uM
Riboflavin	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	8.8000	uM
disodium;2-(2,4,5,7-tetraiodo-3-oxido-6-oxoxanthen-9-yl)benzoate;hydrate	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	9.2000	uM
1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-7-ol	1594135: Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	ic50	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Dexamethasone	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
lead acetate	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
cupric chloride	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
S 1 (combination)	increases response to substance	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4157379	Binding	Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis	Sulfonamido-2-arylbenzoxazole GroEL/ES Inhibitors as Potent Antibacterials against Methicillin-Resistant Staphylococcus aureus (MRSA). — *J Med Chem*
CHEMBL4392929	ADMET	Inhibition of native rhodanese (unknown origin) assessed as reduction in rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis	HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8XV	Ubigene HCT 116 TST KO	Cancer cell line	Male
CVCL_E2MT	HAP1 TST (-) 1	Cancer cell line	Male
CVCL_E2MU	HAP1 TST (-) 2	Cancer cell line	Male
CVCL_E2MV	HAP1 TST (-) 3	Cancer cell line	Male
CVCL_E2MW	HAP1 TST (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TST across ~30M SureChEMBL compounds — explore on Sugi Predict.