ZNF250

Chr 8

zinc finger protein 250

Also known as: ZFP647, ZNF647

NCBI Gene: 58500 ENSG00000196150 UniProt: P15622

ZNF250 encodes a zinc finger transcription factor that binds to specific DNA sequences and regulates gene transcription by RNA polymerase II in the nucleus. The gene is highly constrained against loss-of-function variants (LOEUF 0.499), suggesting mutations would likely cause severe developmental disorders, though specific disease associations have not yet been established. An inheritance pattern has not been determined for ZNF250-related disorders.

ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.50

Clinical Summary— ZNF250

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

49 VUS of 62 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.278

Z-score 3.24

OE 0.24 (0.12–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.34Z-score

OE missense 0.63 (0.57–0.71)

206 obs / 324.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.12–0.50)

0≤0.351.4

Missense OE?0.63 (0.57–0.71)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 5 / 21.1Missense obs/exp: 206 / 324.6Syn Z: 0.22

This gene — mechanism propensity

0.88top 5%

GOF

0.87top 5%

LOF

0.2387th %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

62 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	49	49
Likely Benign	3	3
Benign	0	0
Total	52	52

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

54 pathogenic / likely-pathogenic (of 64) ClinVar copy-number / structural variants overlap ZNF250 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →