ZNF629

Chr 16

zinc finger protein 629

ENSG00000102870 UniProt: Q9UEG4 OMIM: 619587

This protein is predicted to regulate transcription by RNA polymerase II through DNA binding and zinc ion binding activities in the nucleus. The gene is highly constrained against loss-of-function variants (pLI = 1.00, LOEUF = 0.17), suggesting mutations would likely cause severe disease, though specific associated disorders have not yet been established. Any pathogenic variants would be expected to follow autosomal dominant inheritance given the extreme constraint metrics.

OMIM ResearchSummary from RefSeq, UniProt

May be involved in transcriptional regulation

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.17

Clinical Summary— ZNF629

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.78

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

3.86Z-score

OE missense 0.54 (0.49–0.59)

296 obs / 550.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.54 (0.49–0.59)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 1 / 28.5Missense obs/exp: 296 / 550.8Syn Z: 2.47

This gene — mechanism propensity

0.6648th %ile

GOF

0.7126th %ile

LOF

0.54top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.17

GOFprediction above median

DNprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.