MPST

Chr 22

mercaptopyruvate sulfurtransferase

Also known as: MST, TST2, TUM1

The protein is a cytoplasmic sulfurtransferase that transfers sulfur ions to cyanide and other thiol compounds, detoxifies cyanide, and produces hydrogen sulfide in the brain, retina, and vascular endothelium for synaptic modulation and neuroprotection. Mutations cause mercaptolactate-cysteine disulfiduria (MCDU), a rare inherited disorder with autosomal recessive inheritance. This gene shows very low constraint against loss-of-function variants, suggesting tolerance to reduced gene dosage.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.34
Clinical SummaryMPST
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Gene-Disease Validity (ClinGen)
encephalopathy due to beta-mercaptolactate-cysteine disulfiduria · ARNo Known Disease Relationship

No known disease relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 54 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.000
Z-score 0.77
OE 0.75 (0.441.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.21Z-score
OE missense 0.76 (0.670.87)
153 obs / 201.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.441.34)
00.351.4
Missense OE0.76 (0.670.87)
00.61.4
Synonymous OE0.71
01.21.6
LoF obs/exp: 8 / 10.7Missense obs/exp: 153 / 201.4Syn Z: 2.28
DN
0.6454th %ile
GOF
0.6834th %ile
LOF
0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

78 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS54
Likely Benign2
Conflicting1
16
Pathogenic
1
Likely Pathogenic
54
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
52
2
0
54
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Conflicting
1
Total05419074

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MPST · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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