TMEM131L

Chr 4

transmembrane 131 like

Also known as: KIAA0922

NCBI Gene: 23240 ENSG00000121210 UniProt: A2VDJ0 OMIM: 616243

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.

OMIM ResearchSummary from RefSeq, UniProt

Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

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Mechanism