TMEM129

Chr 4

transmembrane protein 129, E3 ubiquitin ligase

Also known as: D4S2561E

NCBI Gene: 92305 ENSG00000168936 UniProt: A0AVI4 OMIM: 615975

The protein functions as an E3 ubiquitin-protein ligase involved in endoplasmic reticulum-associated protein degradation, working with the E2 enzyme UBE2J2 to target misfolded proteins for degradation. Mutations cause autosomal recessive congenital disorders of glycosylation with hepatic, neurologic, and cutaneous involvement, typically presenting in infancy with developmental delay, seizures, and liver dysfunction. The gene shows high constraint against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin protein ligase activity. Involved in protein polyubiquitination; retrograde protein transport, ER to cytosol; and ubiquitin-dependent protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

—

Mechanism