ZNF251

Chr 8

zinc finger protein 251

ZNF251 encodes a DNA-binding transcription factor that regulates gene expression by RNA polymerase II and is predicted to function in hematopoietic stem cell homeostasis. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting that complete loss of function may be tolerated. No established disease associations have been reported for ZNF251 mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.35
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryZNF251
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.000
Z-score 0.32
OE 0.92 (0.641.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.98Z-score
OE missense 0.86 (0.780.94)
317 obs / 369.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.92 (0.641.35)
00.351.4
Missense OE0.86 (0.780.94)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 19 / 20.6Missense obs/exp: 317 / 369.8Syn Z: 1.73
DN
0.90top 5%
GOF
0.83top 10%
LOF
0.2680th %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

ZNF251 · 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.

Search ClinicalTrials.gov →