ZIC4

Chr 3

Zic family zinc finger 4

NCBI Gene: 84107 ENSG00000174963 UniProt: Q8N9L1 OMIM: 608948

This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.000

Z-score 1.95

OE 0.48 (0.28–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.92–1.14)

230 obs / 225.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.28–0.87)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 8 / 16.5Missense obs/exp: 230 / 225.2Syn Z: -1.71

Background carrier burden — how many people carry a rare variant somewhere in ZIC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

662 rare PASS variants

Rare truncating (LoF)

1 in 1,400

75 rare PASS variants

Rare synonymous (reference)

1 in 150

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZIC4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 2,000
South Asian	~43k	1 in 79	1 in 660
Remaining (unassigned)	~30k	1 in 110	1 in 830
European (Finnish)	~27k	1 in 340	≈ 1 in 5,800
Admixed American	~22k	1 in 110	1 in 500
African / African American	~21k	1 in 84	1 in 720
East Asian	~20k	1 in 140	1 in 950
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 5 poorly covered. Genomes: all 4.? see exons ↓