TBCK

Chr 4AR

TBC1 domain containing kinase

Also known as: FERRY1, Fy-1, HSPC302, IHPRF3, TBCKL

NCBI Gene: 93627 ENSG00000145348 UniProt: Q8TEA7 OMIM: 616899

The protein contains a kinase domain and regulates mTOR signaling pathway to control actin organization, cell growth, and cell proliferation. Biallelic mutations cause hypotonia, infantile, with psychomotor retardation and characteristic facies 3, inherited in an autosomal recessive pattern. The pathogenic mechanism involves loss of function, disrupting normal mTOR-mediated cellular processes essential for neuronal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypotonia, infantile, with psychomotor retardation and characteristic facies 3MIM #616900

Clinical highlights

Gene-disease validity (ClinGen)

syndromic complex neurodevelopmental disorder · ARDefinitivesufficient evidence for diagnostic panels

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)

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P/LP submissions

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P/LP missense

0.87

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TBCK