ZIC3

Chr XXLR

Zic family zinc finger 3

Also known as: HTX, HTX1, VACTERLX, ZNF203

NCBI Gene: 7547 ENSG00000156925 UniProt: O60481 OMIM: 300265

The protein functions as a transcriptional activator that binds to GLI-consensus sequences and is required for axial midline development and left-right asymmetry specification during early embryogenesis. Loss-of-function mutations cause X-linked visceral heterotaxy with congenital heart defects and left-right axis defects in organs, as well as VACTERL association. The condition follows X-linked recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital heart defects, nonsyndromic, multiple types, 1, X-linkedMIM #306955

XLR

Heterotaxy, visceral, 1, X-linkedMIM #306955

XLR

VACTERL association, X-linkedMIM #314390

XLR

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease with heterotaxy syndrome · XLDefinitivesufficient evidence for diagnostic panels

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

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P/LP missense

0.36

LOEUF

LOF

Mechanism· G2P