ZNF423

Chr 16ADAR

zinc finger protein 423

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

NCBI Gene: 23090 ENSG00000102935 UniProt: Q2M1K9 OMIM: 604557

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a nuclear protein that belongs to the family of Kruppel-like C2H2 zinc finger proteins. It functions as a DNA-binding transcription factor by using distinct zinc fingers in different signaling pathways. Thus, it is thought that this gene may have multiple roles in signal transduction during development. Mutations in this gene are associated with nephronophthisis-14 and Joubert syndrome-19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.192 OMIM phenotypes

Clinical Summary— ZNF423

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Gene-Disease Validity (ClinGen)

ciliopathy · ARModerate

Moderate evidence — consider for supplementary testing

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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

5 unique Pathogenic / Likely Pathogenic· 491 VUS of 967 total submissions

Explore recent and relevant literature in Research Assistant →

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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

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 5.54

OE 0.07 (0.03–0.19)

Highly constrained

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

Missense Constraint?

2.49Z-score

OE missense 0.76 (0.71–0.81)

625 obs / 826.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.19)

0≤0.351.4

Missense OE?0.76 (0.71–0.81)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 3 / 41.6Missense obs/exp: 625 / 826.5Syn Z: -1.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongZNF423-related Joubert syndromeOTHERAD

This gene — mechanism propensity

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 · 60% of P/LP variants are LoF · 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

967 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic2

VUS491

Likely Benign420

Benign28

Conflicting17

Pathogenic

Likely Pathogenic

491

VUS

420

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	1	1	0	0	2
VUS	4	477	7	3	491
Likely Benign	0	6	55	359	420
Benign	0	2	12	14	28
Conflicting	—				17
Total	7	487	74	376	961

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ZNF423 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →