TM4SF20

Chr 2

transmembrane 4 L six family member 20

Also known as: PRO994, SLI5, TCCE518

NCBI Gene: 79853 ENSG00000168955 UniProt: Q53R12

The encoded protein is a four-transmembrane protein that regulates CREB3L1 activation and collagen synthesis through regulated intramembrane proteolysis, with high expression in multiple brain regions including parietal and occipital lobes, hippocampus, and cerebellum. Mutations cause specific language impairment-5 with autosomal dominant inheritance. The gene shows tolerance to loss-of-function variants (low pLI score), suggesting the pathogenic variants may work through alternative mechanisms.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Knockout of the homologous gene in mouse results in a neurobehavioral phenotype with suggested enhanced motor coordination. A deletion mutation in the human gene is associated with specific language impairment-5. [provided by RefSeq, Jul 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpecific language impairment 5

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.63

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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