TMEM131L
Chr 4transmembrane 131 like
Also known as: KIAA0922
The TMEM131L protein is a membrane-associated regulator that antagonizes canonical Wnt signaling by promoting lysosome-dependent degradation of Wnt-activated LRP6 and regulates thymocyte proliferation in the thymus. Mutations cause autosomal recessive severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation (SCIDMGR), which presents in early infancy with severe immunodeficiency affecting T cell development. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not tolerated in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
306 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 | 24 | 0 | 24 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 234 | 1 | 0 | 235 |
Likely Benign | 0 | 14 | 1 | 2 | 17 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 0 | 249 | 29 | 3 | 281 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM131L · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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