ZNF423

Chr 16ADAR

zinc finger protein 423

Also known as: Ebfaz, JBTS19, NPHP14, OAZ, Roaz, ZFP423, Zfp104, hOAZ

This protein is a DNA-binding transcription factor that plays a central role in BMP signaling, olfactory neurogenesis, and cerebellar vermis formation by controlling proliferation and differentiation of neural precursors. Mutations cause Joubert syndrome-19 and nephronophthisis-14, ciliopathies affecting the brain, kidneys, and other organ systems. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.192 OMIM phenotypes
Clinical SummaryZNF423
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Gene-Disease Validity (ClinGen)
ciliopathy · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 179 VUS of 300 total submissions
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GeneReview available — ZNF423
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.54
OE 0.07 (0.030.19)
Highly constrained

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

Missense Constraint
2.49Z-score
OE missense 0.76 (0.710.81)
625 obs / 826.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.19)
00.351.4
Missense OE0.76 (0.710.81)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 3 / 41.6Missense obs/exp: 625 / 826.5Syn Z: -1.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongZNF423-related Joubert syndromeOTHERAD
DN
0.2399th %ile
GOF
0.2696th %ile
LOF
0.82top 5%

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

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic1
VUS179
Likely Benign108
Benign11
Conflicting1
1
Pathogenic
179
VUS
108
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
173
5
1
179
Likely Benign
0
0
19
89
108
Benign
0
0
10
1
11
Conflicting
1
Total01733591300

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF423 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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