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…

Primary Disease Associations & Inheritance

Joubert syndrome 19MIM #614844

ADAR

Nephronophthisis 14MIM #614844

ADAR

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · ciliopathy · AR · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

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

Background carrier burden — how many people carry a rare variant somewhere in ZNF423?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,432 rare PASS variants

Rare truncating (LoF)

1 in 870

37 rare PASS variants

Rare synonymous (reference)

1 in 35

794 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF423. 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 36	1 in 4,300
South Asian	~43k	1 in 37	1 in 2,300
Remaining (unassigned)	~30k	1 in 34	1 in 5,000
European (Finnish)	~27k	1 in 70	1 in 4,400
Admixed American	~22k	1 in 34	1 in 800
African / African American	~21k	1 in 49	≈ 1 in 8,400
East Asian	~20k	1 in 44	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 120	none seen
Middle Eastern	~2,884	1 in 30	none seen

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.