MPST

Summary

MPST (mercaptopyruvate sulfurtransferase, HGNC:7223) is a protein-coding gene on chromosome 22q12.3, encoding 3-mercaptopyruvate sulfurtransferase (P25325). Transfer of a sulfur ion to cyanide or to other thiol compounds.

This protein encoded by this gene catalyzes the transfer of a sulfur ion from 3-mercaptopyruvate to cyanide or other thiol compounds. It may be involved in cysteine degradation and cyanide detoxification. There is confusion in literature between this protein (mercaptopyruvate sulfurtransferase, MPST), which appears to be cytoplasmic, and thiosulfate sulfurtransferase (rhodanese, TST, GeneID:7263), which is a mitochondrial protein. Deficiency in MPST activity has been implicated in a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). Alternatively spliced transcript variants encoding same or different isoforms have been identified for this gene.

Source: NCBI Gene 4357 — RefSeq curated summary.

At a glance

• Gene–disease (curated): encephalopathy due to beta-mercaptolactate-cysteine disulfiduria (No Known Disease Relationship, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 56 total
• GTEx eGene: eQTL in 30 tissues, sQTL in 38 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.50 (unconstrained)
• MANE Select transcript: NM_021126
• Notable: 56 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7223
Approved symbol	MPST
Name	mercaptopyruvate sulfurtransferase
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MST, TST2, TUM1
Ensembl gene	ENSG00000128309
Ensembl biotype	protein_coding
OMIM	602496
Entrez	4357

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 21 protein_coding, 9 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000429360

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

ENST00000429360, ENST00000341116, ENST00000397225, ENST00000401419, ENST00000404393, ENST00000404802, ENST00000485587, ENST00000865000, ENST00000865001, ENST00000865002, ENST00000865003, ENST00000865004, ENST00000935191, ENST00000935192, ENST00000935193, ENST00001004231, ENST00001004232, ENST00001004233, ENST00001004234, ENST00001004235, ENST00001004236, ENST00001004238, ENST00001004239, ENST00001004240, ENST00001004241, ENST00001004244, ENST00001095797, ENST00001118293, ENST00001126534, ENST00001126535, ENST00001132149

RefSeq mRNA: 5 — MANE Select: NM_021126 NM_001013436, NM_001130517, NM_001369904, NM_001369905, NM_021126

CCDS: CCDS13939, CCDS46703

Canonical transcript exons

ENST00000429360 — 3 exons

Exon	Start	End
ENSE00001958450	37029216	37029815
ENSE00003763753	37024192	37024810
ENSE00003765684	37019742	37019872

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5938 / max 299.4998, expressed in 1779 samples.

Highest expression (Bgee): mucosa of transverse colon, lobe of liver, lower esophagus mucosa, liver, transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MPST is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 38 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 68 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	6.5e-34	-1.32	22:37023301:T:C
Skin Sun Exposed Lower leg	sqtl	5.5e-28	-1.13	22:37023301:T:C
Adipose Subcutaneous	sqtl	8.3e-27	-1.15	22:37023301:T:C
Esophagus Mucosa	sqtl	4.3e-21	-1.13	22:37023301:T:C
Cells Cultured fibroblasts	eqtl	2.6e-20	+0.74	22:37019732:GC:G
Thyroid	eqtl	1.2e-19	-0.22	22:37021156:T:C
Skin Not Sun Exposed Suprapubic	sqtl	7.7e-19	-1.05	22:37023301:T:C
Whole Blood	eqtl	1.9e-17	+0.60	22:37019732:GC:G
Pancreas	sqtl	4.2e-17	-1.34	22:37023301:T:C
Testis	sqtl	5.8e-17	-1.59	22:37027101:T:C
Muscle Skeletal	sqtl	7.4e-17	-0.96	22:37023301:T:C
Esophagus Muscularis	sqtl	7.6e-17	-1.08	22:37023301:T:C
Testis	eqtl	3.8e-16	+0.44	22:37026349:C:G
Colon Transverse	sqtl	4.4e-16	-1.03	22:37023301:T:C
Colon Transverse	eqtl	1.9e-15	-0.24	22:37018942:G:A
Adipose Visceral Omentum	sqtl	2.9e-15	-0.97	22:37027101:T:C
Cells Cultured fibroblasts	sqtl	3.0e-15	-1.01	22:37023301:T:C
Heart Atrial Appendage	sqtl	3.7e-15	-1.11	22:37023301:T:C
Breast Mammary Tissue	sqtl	7.3e-15	-1.12	22:37023301:T:C
Artery Tibial	sqtl	4.8e-14	-0.96	22:37023301:T:C

FANTOM5 promoters

showing 10 of 14 alternative TSS:

Promoter ID	TPM avg	Samples expressed
192094	11.9340	1749
192095	4.6791	1451
192099	1.8915	958
192093	0.9846	699
192100	0.2111	85
192097	0.1949	23
192102	0.1794	61
192101	0.1512	49
192092	0.1159	31
192103	0.1079	20

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.92	gold quality
right lobe of liver	UBERON:0001114	98.71	gold quality
lower esophagus mucosa	UBERON:0035834	97.52	gold quality
liver	UBERON:0002107	97.03	gold quality
transverse colon	UBERON:0001157	96.58	gold quality
body of pancreas	UBERON:0001150	96.34	gold quality
ileal mucosa	UBERON:0000331	95.81	gold quality
left ovary	UBERON:0002119	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.55	gold quality
right ovary	UBERON:0002118	95.51	gold quality
duodenum	UBERON:0002114	95.40	gold quality
body of stomach	UBERON:0001161	95.35	gold quality
mucosa of stomach	UBERON:0001199	95.30	gold quality
esophagus mucosa	UBERON:0002469	95.04	gold quality
skin of abdomen	UBERON:0001416	94.99	gold quality
small intestine	UBERON:0002108	94.92	gold quality
gastrocnemius	UBERON:0001388	94.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.89	gold quality
skin of leg	UBERON:0001511	94.66	gold quality
right lung	UBERON:0002167	94.36	gold quality
right adrenal gland	UBERON:0001233	94.32	gold quality
esophagus	UBERON:0001043	94.14	gold quality
right adrenal gland cortex	UBERON:0035827	94.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.09	gold quality
muscle of leg	UBERON:0001383	93.81	gold quality
colon	UBERON:0001155	93.75	gold quality
right atrium auricular region	UBERON:0006631	93.74	gold quality
lower esophagus	UBERON:0013473	93.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.60	gold quality
large intestine	UBERON:0000059	93.57	gold quality
intestine	UBERON:0000160	93.56	gold quality
left adrenal gland	UBERON:0001234	93.56	gold quality
left adrenal gland cortex	UBERON:0035825	93.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.35	gold quality
adrenal cortex	UBERON:0001235	93.27	gold quality
omental fat pad	UBERON:0010414	93.20	gold quality
zone of skin	UBERON:0000014	93.19	gold quality
heart left ventricle	UBERON:0002084	93.16	gold quality
peritoneum	UBERON:0002358	93.15	gold quality
fundus of stomach	UBERON:0001160	93.13	gold quality
stomach	UBERON:0000945	93.10	gold quality
adult mammalian kidney	UBERON:0000082	92.96	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.96	gold quality
cardiac ventricle	UBERON:0002082	92.91	gold quality
cardiac atrium	UBERON:0002081	92.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.67	gold quality
apex of heart	UBERON:0002098	92.46	gold quality
sigmoid colon	UBERON:0001159	92.36	gold quality
jejunal mucosa	UBERON:0000399	92.35	gold quality
muscle organ	UBERON:0001630	92.07	gold quality
left coronary artery	UBERON:0001626	91.98	gold quality
left testis	UBERON:0004533	91.94	gold quality
left uterine tube	UBERON:0001303	91.91	gold quality
right testis	UBERON:0004534	91.85	gold quality
colonic mucosa	UBERON:0000317	91.80	gold quality
coronary artery	UBERON:0001621	91.76	gold quality
heart	UBERON:0000948	91.75	gold quality
triceps brachii	UBERON:0001509	91.71	gold quality
tibial nerve	UBERON:0001323	91.67	gold quality
ovary	UBERON:0000992	91.64	gold quality
minor salivary gland	UBERON:0001830	91.55	gold quality
descending thoracic aorta	UBERON:0002345	91.50	gold quality
thoracic aorta	UBERON:0001515	91.42	gold quality
ascending aorta	UBERON:0001496	91.36	gold quality
saliva-secreting gland	UBERON:0001044	91.31	gold quality
mouth mucosa	UBERON:0003729	91.31	gold quality
upper lobe of left lung	UBERON:0008952	91.28	gold quality
ectocervix	UBERON:0012249	91.28	gold quality
ventricular zone	UBERON:0003053	91.24	gold quality
aorta	UBERON:0000947	91.22	gold quality
vagina	UBERON:0000996	91.12	gold quality
popliteal artery	UBERON:0002250	91.11	gold quality
tibial artery	UBERON:0007610	91.08	gold quality
adrenal gland	UBERON:0002369	91.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.05	gold quality
stromal cell of endometrium	CL:0002255	91.03	gold quality
jejunum	UBERON:0002115	91.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.89	gold quality
upper lobe of lung	UBERON:0008948	90.85	gold quality
embryo	UBERON:0000922	90.78	gold quality
adipose tissue	UBERON:0001013	90.72	gold quality
pharyngeal mucosa	UBERON:0000355	90.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.65	gold quality
metanephros cortex	UBERON:0010533	90.41	gold quality
body of uterus	UBERON:0009853	90.28	gold quality
endocervix	UBERON:0000458	90.26	gold quality
putamen	UBERON:0001874	90.22	gold quality
connective tissue	UBERON:0002384	90.18	gold quality
spinal cord	UBERON:0002240	89.98	gold quality
nipple	UBERON:0002030	89.96	gold quality
ganglionic eminence	UBERON:0004023	89.96	gold quality
right coronary artery	UBERON:0001625	89.78	gold quality
mammalian vulva	UBERON:0000997	89.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.62	gold quality
body of tongue	UBERON:0011876	89.48	gold quality
testis	UBERON:0000473	89.12	gold quality
skeletal muscle tissue	UBERON:0001134	89.12	gold quality
monocyte	CL:0000576	89.09	gold quality
mononuclear cell	CL:0000842	88.87	gold quality
gluteal muscle	UBERON:0002000	88.69	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	1366.32
E-HCAD-4	yes	144.94
E-HCAD-6	yes	57.04
E-MTAB-8410	yes	15.03
E-ENAD-27	no	4.32
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	116.2	medium
Duodenum	tissue	100.2	high
Small intestine	tissue	87.7	high
Vagina	tissue	58.8	low
Pancreas	tissue	56.0	medium
Colon	tissue	54.4	medium
Choroid plexus	tissue	45.4
Frontal cortex	tissue	39.4
Salivary gland	tissue	37.2	low
Stomach 1	tissue	35.9	medium
Skeletal muscle	tissue	35.2	not detected
Ovary	tissue	34.4	medium
Bone marrow	tissue	34.4	low
Caudate putamen	tissue	32.2
Hippocampus	tissue	30.3	low
Nucleus accumbens	tissue	29.0
Locus coeruleus	tissue	28.7
Adipose tissue	tissue	25.6	medium
Kidney	tissue	23.3	medium
Tongue	tissue	21.5
Esophagus	tissue	21.3	not detected
Skin 1	tissue	20.0	medium
Adrenal gland	tissue	19.1	medium
Heart muscle	tissue	18.1	not detected
Cervix	tissue	17.7	medium
Postcentral gyrus	tissue	16.6
Rectum	tissue	16.0	medium
Gallbladder	tissue	15.5	medium
Lung	tissue	15.3	medium
Pituitary gland	tissue	14.1
Prostate	tissue	13.8	medium
Testis	tissue	12.3	medium
Fallopian tube	tissue	11.5	medium
Endometrium 1	tissue	10.3	medium
Urinary bladder	tissue	9.9	medium
Appendix	tissue	9.5	medium
Seminal vesicle	tissue	9.1	medium
Placenta	tissue	8.5	medium
Lymph node	tissue	8.3	low
Corpus callosum	tissue	7.9
Spleen	tissue	7.8	not detected
Spinal cord	tissue	7.7
Putamen	tissue	7.6
Breast	tissue	7.5	medium
Periaqueductal gray	tissue	7.0
Medulla oblongata	tissue	6.7
Substantia nigra	tissue	6.6
Smooth muscle	tissue	6.5	not detected
Thyroid gland	tissue	6.3	medium
Hypothalamus	tissue	6.2
Midbrain	tissue	5.8
Pons	tissue	5.7
Tonsil	tissue	5.7	medium
Thalamus	tissue	5.5
Hippocampal formation	tissue	5.3
Superior colliculi	tissue	5.2
Septum	tissue	5.0
Amygdala	tissue	4.9
Olfactory bulb	tissue	4.9
Basal ganglia	tissue	4.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Temporal white matter (54.5), Nucleus ambiguus (53.1), Parieto-temporal junction (white matter) (50.5), Globus pallidus, externus (49.0), Area striata (white matter) (48.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

Functional genomics

gnomAD constraint: pLI 2.4e-09, LOEUF 1.5, missense Z -1.31 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000429360 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 14)

• This work is the first report of a functional genetic polymorphism affecting MPST and should help in investigation of disorders such as mercaptolactate-cysteine disulfiduria. (PMID:16545926)
• Data suggest that impaired rhodanese expression is associated with increased whole cell reactive oxygen species as well as higher mitochondrial superoxide production and predicts mortality in hemodialysis patients. (PMID:19695240)
• In all the investigated cell lines, the activity of MPST was higher than that of CST, which suggests that in these cells, the main pathway of sulfane sulfur formation is the MPST-catalyzed reaction. (PMID:20446008)
• The crystal structure analysis allows us to propose a detailed mechanism for MST in which an Asp-His-Ser catalytic triad is positioned to activate the nucleophilic cysteine residue and participate in general acid-base chemistry (PMID:23698001)
• distinct roles of each TUM1 isoform in the sulfur transfer processes in the cell (PMID:25336638)
• In this review, we discuss the roles of non-canonical Hippo/Mst signaling pathways in lymphocyte development and functions. [review] (PMID:25487919)
• 3-Mercaptopyruvate sulphurtransferase and not cystathionine gamma-lyase is the primary regulator of coronary artery hydrogen sulfide production and function. (PMID:26519030)
• 3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics. (PMID:30644090)
• MPST inactivation or silencing enhances the plasticity of dermal fibroblasts in a TET1 and glycolysis dependent manner and promotes adipogenic transdifferentiation. (PMID:31634482)
• Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. (PMID:32179647)
• 3-Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma. (PMID:35243746)
• MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT. (PMID:36126419)
• 3-Mercaptopyruvate sulfur transferase is a protein persulfidase. (PMID:36732619)
• Role of the 3-mercaptopyruvate sulfurtransferase in colon/colorectal cancers. (PMID:38631098)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mpst	ENSMUSG00000071711
rattus_norvegicus	Mpst	ENSRNOG00000000185
caenorhabditis_elegans		WBGENE00008409
caenorhabditis_elegans		WBGENE00010380
caenorhabditis_elegans		WBGENE00010383
caenorhabditis_elegans		WBGENE00011307
caenorhabditis_elegans		WBGENE00017387
caenorhabditis_elegans		WBGENE00022006
caenorhabditis_elegans		WBGENE00022007

Paralogs (1): TST (ENSG00000128311)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2179733) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased exploration in new environment	2
increased Leydig cell number	1
increased anxiety-related response	1
reduced male fertility	1
male infertility	1
testis hypoplasia	1
abnormal spermatocyte morphology	1
increased serotonin level	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
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
Pseudomonas aeruginosa PAO1	Q9I452	42.8%	Diamond
Schizosaccharomyces pombe 972h-	Q9USJ1	41.0%	Diamond
Saccharomyces cerevisiae S288C	Q08686	36.9%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O26719	34.9%	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
TST	protein-coding	7263
IL2RB-AS1	ncRNA	139281655
TMPRSS6	protein-coding	164656
IL2RB	protein-coding	3560
KCTD17	protein-coding	79734
LL22NC01-81G9.3	ncRNA	100506241

Protein

Protein identifiers

3-mercaptopyruvate sulfurtransferase — P25325 (reviewed: P25325)

All UniProt accessions (3): A0A140VJX3, B1AH49, P25325

UniProt curated annotations — full annotation on UniProt →

Function. Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions.

Subunit / interactions. Monomer (active form). Homodimer; disulfide-linked (inactive form).

Subcellular location. Cytoplasm. Mitochondrion. Synapse. Synaptosome.

Disease relevance. Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine. Some cases have associated intellectual disability.

Activity regulation. By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme.

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.

Miscellaneous. Thioredoxin (Trx) or dihydrolipoic acid (DHLA) are required to release hydrogen sulfide from the persulfide intermediate.

Isoforms (2)

UniProt ID	Names	Canonical?
P25325-1	1	yes
P25325-2	2

RefSeq proteins (5): NP_001013454, NP_001123989, NP_001356833, NP_001356834, NP_066949* (*=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

Enzyme classification (BRENDA)

• EC 2.8.1.2 — 3-mercaptopyruvate sulfurtransferase (BRENDA: 12 organisms, 45 substrates, 35 inhibitors, 78 Km, 47 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-MERCAPTOPYRUVATE	0.015–73	48
CYANIDE	1.66–6	4
L-CYSTEINE	3.8–6	4
THIOREDOXIN	0.0025–0.0031	4
DITHIOTHREITOL	2.59–4.6	3
N-ACETYL-L-CYSTEINE	11.4–17	3
2-MERCAPTOETHANOL	19–108	2
THIOSULFATE	1.7–266	2
CYSTEINE	8.2	1
DIHYDROLIPOIC ACID	4.4	1
GLUTATHIONE	28	1
L-HOMOCYSTEINE	12.5	1
REDUCED THIOREDOXIN	0.3	1

Catalyzed reactions (Rhea)

• 2-oxo-3-sulfanylpropanoate + [thioredoxin]-dithiol = [thioredoxin]-disulfide + hydrogen sulfide + pyruvate + H(+) (RHEA:21740)

UniProt features (45 total): helix 15, modified residue 9, strand 9, sequence conflict 2, domain 2, initiator methionine 1, chain 1, disulfide bond 1, splice variant 1, turn 1, region of interest 1, active site 1, binding site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
4JGT	Structure and kinetic analysis of H2S production by human Mercaptopyruvate …	X-RAY DIFFRACTION	2.16
3OLH	Human 3-mercaptopyruvate sulfurtransferase	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25325-F1	95.74	0.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; cytosol

Antibody reliability (HPA): IH enhanced · IF approved

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 (1)

Position	Role
188	substrate

Post-translational modifications (9)

Type	Positions
N6-acetyllysine	40
N6-succinyllysine	40, 146, 164
Phosphoserine	15, 23, 3, 35
N-acetylalanine	2

Disulfide bonds (1)

Type	Positions
Interchain (with c-264)	264

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 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-1614635	Sulfur amino acid metabolism	—

MSigDB gene sets: 150 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GOBP_TRNA_METABOLIC_PROCESS, GOBP_HOMOCYSTEINE_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (9): sulfur amino acid catabolic process (GO:0000098), kidney development (GO:0001822), liver development (GO:0001889), tRNA wobble position uridine thiolation (GO:0002143), cyanate catabolic process (GO:0009440), response to toxic substance (GO:0009636), transsulfuration (GO:0019346), spinal cord development (GO:0021510), hydrogen sulfide biosynthetic process (GO:0070814)

GO Molecular Function (6): thiosulfate-cyanide sulfurtransferase activity (GO:0004792), sulfurtransferase activity (GO:0016783), 3-mercaptopyruvate sulfurtransferase activity (GO:0016784), identical protein binding (GO:0042802), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), neuron projection (GO:0043005), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

3 top-level categories:

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

GO top-level categories

31 GO namespaces:

Category	Terms
sulfurtransferase activity	2
sulfur amino acid metabolic process	1
sulfur compound catabolic process	1
carboxylic acid catabolic process	1
animal organ development	1
renal system development	1
gland development	1
hepaticobiliary system development	1
tRNA wobble uridine modification	1
tRNA thio-modification	1
catabolic process	1
response to chemical	1
homocysteine metabolic process	1
proteinogenic amino acid metabolic process	1
central nervous system development	1
animal gross anatomical part developmental process	1
sulfur compound biosynthetic process	1
hydrogen sulfide metabolic process	1
transferase activity, transferring sulphur-containing groups	1
protein binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
plasma membrane bounded cell projection	1
cell junction	1
extracellular vesicle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
mitochondrion	CC	high-throughput

Protein interactions and networks

STRING

showing 15 of 860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPST	CTH	P32929	929
MPST	P0DN79	P0DN79	903
MPST	H7C2H4	H7C2H4	903
MPST	RET	P07949	876
MPST	SUOX	P51687	772
MPST	ETHE1	O95571	758
MPST	SQOR	Q9Y6N5	734
MPST	DAO	P14920	727
MPST	MOCS3	O95396	708
MPST	CTU1	Q7Z7A3	682
MPST	URM1	Q9BTM9	655
MPST	NFS1	Q9Y697	607
MPST	CARS1	P49589	593
MPST	CDO1	P78513	550
MPST	CARS2	Q9HA77	550

IntAct

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

4 partners by confidence:

Partner	Interaction type	MIscore	Records
AKT1	physical association	0.570	3
ZBED1	physical association	0.560	3
PCNA	physical association	0.370	1
TFAP2A	physical association	0.370	1

BioGRID (71 interactions; top human partners by supporting records): CLPP (Proximity Label-MS; 2 records), ACO2 (Co-fractionation), ALDH4A1 (Co-fractionation), ANXA4 (Co-fractionation), BID (Co-fractionation), C1orf198 (Co-fractionation), C21orf33 (Co-fractionation), CLIC4 (Co-fractionation), CMPK1 (Co-fractionation), CRYZ (Co-fractionation), CTSB (Co-fractionation), CTSD (Co-fractionation), DDAH2 (Co-fractionation), DISC1 (Affinity Capture-MS), EIF2B1 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for MPST: 56 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 391):

Position(s)	Effect	Δscore	Sites
22:37029211	acceptor_gain	0.9900
22:37029214–37029215	acceptor_loss	0.9800	6
22:37024776	donor_gain	0.9700
22:37029200	acceptor_gain	0.9600
22:37029208	acceptor_gain	0.9600
22:37019873–37019874	donor_loss	0.9500	6
22:37024170	acceptor_gain	0.9300
22:37019875	donor_loss	0.9200
22:37019875	donor_loss	0.9100
22:37024190–37024191	acceptor_loss	0.9000	5

AlphaMissense

677 missense substitutions predicted likely pathogenic (of 2,048 scored), across 178 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
D182	8	0.984	0.992
D101	8	0.961	0.987
D33	8	0.953	0.970
D273	8	0.942	0.970
F82	8	0.924	0.983
F117	8	0.888	0.974
F233	8	0.883	0.973
F60	8	0.882	0.975
H74	8	0.880	0.964
N172	8	0.798	0.950
W276	7	0.978	0.994
F189	7	0.971	0.995
W279	7	0.959	0.990
F49	7	0.949	0.992
W114	7	0.936	0.984
F120	7	0.927	0.982
W135	7	0.919	0.980
C248	7	0.919	0.982
F213	7	0.909	0.987
R188	7	0.905	0.969

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	1.71e-05
Glioblastoma Multiforme (TCGA)	favorable	0.000154

Disease associations

OMIM: gene MIM:602496 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
encephalopathy due to beta-mercaptolactate-cysteine disulfiduria	No Known Disease Relationship	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
encephalopathy due to beta-mercaptolactate-cysteine disulfiduria	No Known Disease Relationship	AR

Mondo (1): encephalopathy due to beta-mercaptolactate-cysteine disulfiduria (MONDO:0009585)

GWAS associations

1 associations:

Study	Trait	p-value
GCST007457_8	Eye color (saturation)	5e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009764	eye colour measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C563085	Mercaptolactate-Cysteine Disulfiduria *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066937 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrogen sulphide synthesis

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
I3MT-3	Inhibition	5.57	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, increases methylation	4
bisphenol A	decreases expression, increases expression, affects expression	3
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Smoke	increases abundance, increases expression, decreases expression	2
1-Methyl-4-phenylpyridinium	increases expression, decreases expression	2
FR900359	increases phosphorylation	1
bismuth tripotassium dicitrate	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651808	Binding	Binding affinity to human MPST incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3B7	Abcam HEK293T MPST KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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