TMEM135
Chr 11transmembrane protein 135
Also known as: PMP52
TMEM135 encodes a protein that regulates mitochondrial dynamics by controlling the balance between mitochondrial fusion and fission, and may also function in peroxisome organization and fatty acid transport. Mutations cause autosomal recessive spastic paraplegia with onset typically in childhood or adolescence, characterized by progressive lower limb spasticity and weakness. The gene shows significant constraint against loss-of-function variants (LOEUF 0.39), indicating that complete loss of protein function is likely poorly tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
110 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 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 42 | 7 | 0 | 49 |
Likely Benign | 0 | 4 | 1 | 1 | 6 |
Benign | 0 | 4 | 1 | 1 | 6 |
| Total | 0 | 50 | 29 | 2 | 81 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM135 · 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