ZFHX3

Chr 16ADAR

zinc finger homeobox 3

Also known as: ATBF1, ATBT, ATFB8, C16orf47, EIG20, SCA4, ZFH-3, ZNF927

NCBI Gene: 463 ENSG00000140836 UniProt: Q15911 OMIM: 104155

This gene encodes a transcription factor that regulates myogenic and neuronal differentiation and controls circadian locomotor rhythms in the brain. Mutations cause spinocerebellar ataxia 4, idiopathic generalized epilepsy, and susceptibility to atrial fibrillation with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.136), indicating intolerance to protein-truncating mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Atrial fibrillation 8, susceptibility to}MIM #613055

Epilepsy, idiopathic generalized 20MIM #621500

Prostate cancer, somaticMIM #176807

Spinocerebellar ataxia 4MIM #600223

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

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — ZFHX3