ZHX2

Chr 8

zinc fingers and homeoboxes 2

Also known as: AFR1, RAF

ZHX2 encodes a nuclear transcriptional repressor containing zinc fingers and homeobox DNA-binding domains that regulates gene expression during neural and retinal development, particularly promoting bipolar OFF-type cell differentiation in the retina and maintaining neural progenitor cells in the developing cortex. Mutations in ZHX2 cause neurodevelopmental disorders with autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF = 0.518), suggesting some tolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
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0
Active trials
13
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.52
LOEUF
Mechanism
Clinical SummaryZHX2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.034
Z-score 3.49
OE 0.29 (0.170.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.76Z-score
OE missense 0.90 (0.840.98)
452 obs / 499.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.170.52)
00.351.4
Missense OE0.90 (0.840.98)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 8 / 27.9Missense obs/exp: 452 / 499.7Syn Z: -1.51

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZHX2 · 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.

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Clinical Literature
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