TMX2

Chr 11

thioredoxin related transmembrane protein 2

Also known as: CGI-31, NEDMCMS, PDIA12, PIG26, TXNDC14

NCBI Gene: 51075 ENSG00000213593 UniProt: Q9Y320

The protein is a disulfide isomerase that catalyzes protein folding and thiol-disulfide reactions in the endoplasmic reticulum and regulates cellular redox state, protein folding, and mitochondrial activity. Biallelic mutations cause neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.47), indicating intolerance to protein-disrupting changes.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This protein is enriched on the mitochondria-associated-membrane of the ER via palmitoylation of two of its cytosolically exposed cysteines. [provided by RefSeq, Jan 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with microcephaly, cortical malformations, and spasticity

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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