ZIC2

Chr 13

Zic family zinc finger 2

Also known as: HPE5

NCBI Gene: 7546ENSG00000043355UniProt: O95409

This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHoloprosencephaly 5

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.
0
Active trials
26
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — ZIC2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.27LOEUF
pLI 0.974
Z-score 3.10
OE 0.00 (0.00–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.21Z-score
OE missense 0.41 (0.35–0.49)
98 obs / 237.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.27)
0≤0.351.4
Missense OE?0.41 (0.35–0.49)
0≤0.61.4
Synonymous OE?1.37
0≤1.21.6
LoF obs/exp: 0 / 11.2Missense obs/exp: 98 / 237.2Syn Z: -2.95

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ZIC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients