TMEM129
protein-codingtransmembrane protein 129, E3 ubiquitin ligase
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMEM129 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001127266.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 77 | 6 | 83 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 78 | 7 | 0 | 85 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001120738.1 | 4 | MANE Select | |
| Ensembl | ENSP00000372394.3 | 4 | MANE Select | |
| RefSeq | NP_612394.1 | 3 | Standard | |
| Ensembl | ENSP00000305243.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Protein ubiquitination
- E3 ubiquitin ligases ubiquitinate target proteins
Biological Process
- protein polyubiquitination
- response to unfolded protein
- protein ubiquitination
- ubiquitin-dependent ERAD pathway
- retrograde protein transport, ER to cytosol
Molecular Function
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382936
- Coding exons
- 4
- Length
- 5407
- Individuals with no LoFs
- 125019
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125036
- p
- 0.0000680
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.925 | 170 | 208 | 0.819 | 0.0000132 | 2271 |
| Missense (PolyPhen) | 46 | 64.179 | 0.71674 | 792 | ||
| Synonymous | 0.455 | 82 | 87.4 | 0.938 | 0.00000539 | 764 |
| Loss of Function | -0.598 | 15 | 12.7 | 1.18 | 6.34e-7 | 140 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase involved in ER-associated protein degradation, preferentially associates with the E2 enzyme UBE2J2. Exploited by viral US11 proteins to mediate HLA class I proteins degradation. {ECO:0000269|PubMed:24807418}.;
Intolerance Scores
- LoFtool
- 0.886
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.469
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |