MPST

Inheritance Pattern: AR

Disease ID:MONDO:0009585

Submitter: ClinGen

The gene *MPST* encodes mercaptopyruvate sulfurtransferase, an enzyme that catalyzes the desulfuration of 3-mercaptopyruvate to generate enzyme bound persulfide and pyruvate. MPST also catalyzes the transfer of sulfur atoms from the persulfide to proteins and small thiol molecule acceptors. A deficiency in MPST enzymatic activity has been identified in relation to mercaptolactate-cysteine disulfiduria (MCDU), a rare autosomal recessive metabolic disorder originally associated with intellectual disability in 1968 by Crawhall et al. (PMID:5644041). Since then, several phenotypically normal individuals and individuals with intellectual disability have been identified with MCDU (PMIDs:4690911, 6945862). However, to date no individuals have been identified with biallelic variants in MPST resulting in MCDU or a deficiency in MPST enzymatic activity. One individual carrying a nonsense variant in the heterozygous state, which results in null enzymatic activity in yeast, displayed a normal MPST phenotype (PMID:16545926). Support for a potential gene-disease relationship comes from the biochemical function of MPST (PMID:33055309), which normally functions to convert cysteine-derived 3-mercaptopyruvate (3MP) to pyruvate, but when absent causes 3- mercaptopyruvate to be converted to 3-mercaptolactate (3ML). Individuals with urinary accumulations of 3ML were originally associated with MPST deficiency and MCDU. Additionally, a knock out MPST (-/-) mouse model demonstrated that KO mice were phenotypically normal besides elevated urinary mercaptolactate excretion and elevated passive systemic anaphylactic responses (PMID: 32012740). In summary, there is insufficient genetic evidence to support a gene-disease relationship. A classification of No Known Disease Relationship was approved by the General IEM GCEP on 04/28/2023.