TMEM129
Chr 4transmembrane protein 129, E3 ubiquitin ligase
Also known as: D4S2561E
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 67 | 0 | 67 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 15 | 10 | 0 | 25 |
Likely Benign | 0 | 1 | 2 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 16 | 84 | 0 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM129 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools