ZIC5

Chr 13

Zic family zinc finger 5

The ZIC5 protein is a zinc finger transcription factor essential for neural crest development, converting cells from epidermal fate to neural crest cell fate. Mutations cause autosomal dominant developmental disorders affecting neural crest-derived structures. The gene shows moderate constraint against loss-of-function variants (pLI 0.77, LOEUF 0.52), suggesting haploinsufficiency may be clinically relevant.

Summary from RefSeq, UniProt
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0
Active trials
5
Pubs (1 yr)
95
P/LP submissions
0%
P/LP missense
0.52
LOEUF
LOF
Mechanism· predicted
Clinical SummaryZIC5
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
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ClinVar Variants
95 unique Pathogenic / Likely Pathogenic· 139 VUS of 257 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.765
Z-score 2.49
OE 0.11 (0.040.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.96Z-score
OE missense 0.83 (0.740.93)
205 obs / 247.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.040.52)
00.351.4
Missense OE0.83 (0.740.93)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 1 / 9.1Missense obs/exp: 205 / 247.6Syn Z: 0.59
DN
0.5082th %ile
GOF
0.3590th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

257 submitted variants in ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic2
VUS139
Likely Benign15
Benign5
93
Pathogenic
2
Likely Pathogenic
139
VUS
15
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
93
0
93
Likely Pathogenic
0
0
2
0
2
VUS
0
130
9
0
139
Likely Benign
0
10
1
4
15
Benign
0
1
4
0
5
Total01411094254

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZIC5 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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