MPST

Chr 22

mercaptopyruvate sulfurtransferase

Also known as: MST, TST2, TUM1

NCBI Gene: 4357 ENSG00000128309 UniProt: P25325 OMIM: 602496

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.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.34

Clinical Summary— MPST

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Gene-Disease Validity (ClinGen)

encephalopathy due to beta-mercaptolactate-cysteine disulfiduria · ARNo Known Disease Relationship

No known disease relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.77

OE 0.75 (0.44–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.21Z-score

OE missense 0.76 (0.67–0.87)

153 obs / 201.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.44–1.34)

0≤0.351.4

Missense OE?0.76 (0.67–0.87)

0≤0.61.4

Synonymous OE?0.71

0≤1.21.6

LoF obs/exp: 8 / 10.7Missense obs/exp: 153 / 201.4Syn Z: 2.28

This gene — mechanism propensity

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.