ZFP37

Chr 9

ZFP37 zinc finger protein

This gene encodes a zinc finger transcription factor that may regulate gene expression and is thought to control nucleolar and centromeric structures in neurons. Mutations cause an autosomal dominant neurodevelopmental disorder through a dominant-negative mechanism. The gene shows tolerance to loss-of-function variants, consistent with dominant-negative pathogenicity rather than haploinsufficiency.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
MultiplemechanismLOEUF 1.32
Clinical SummaryZFP37
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.32LOEUF
pLI 0.000
Z-score 0.40
OE 0.91 (0.641.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.94 (0.861.04)
300 obs / 317.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.91 (0.641.32)
00.351.4
Missense OE0.94 (0.861.04)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 20 / 22.0Missense obs/exp: 300 / 317.6Syn Z: -0.51
DN
0.85top 10%
GOF
0.74top 25%
LOF
0.3258th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZFP37 · 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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