TBC1D20

Chr 20AR

TBC1 domain family member 20

Also known as: C20orf140, WARBM4

NCBI Gene: 128637 ENSG00000125875 UniProt: Q96BZ9 OMIM: 611663

This gene encodes a GTPase-activating protein that accelerates GTP hydrolysis for Rab1, Rab2, and RAB18 small GTPases and is involved in maintaining endoplasmic reticulum structure. Mutations cause Warburg micro syndrome 4, an autosomal recessive disorder characterized by congenital microcephaly, microphthalmia, congenital cataracts, and intellectual disability. The gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.36), consistent with its role in this severe early-onset developmental syndrome.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that belongs to a family of GTPase activator proteins of Rab-like small GTPases. The encoded protein and its cognate GTPase, Rab1, bind the nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) to mediate viral replication. Depletion of this protein inhibits replication of the virus and HCV infection. Mutations in this gene are associated with Warburg micro syndrome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Warburg micro syndrome 4MIM #615663

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TBC1D20