ZNF250

Chr 8

zinc finger protein 250

Also known as: ZFP647, ZNF647

NCBI Gene: 58500ENSG00000196150UniProt: 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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
54
P/LP submissions
0%
P/LP missense
0.50
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ZNF250
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 58 VUS of 125 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 OE0.24 (0.12–0.50)
0≤0.351.4
Missense OE0.63 (0.57–0.71)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 5 / 21.1Missense obs/exp: 206 / 324.6Syn Z: 0.22
DN
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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic5
VUS58
Likely Benign3
49
Pathogenic
5
Likely Pathogenic
58
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
5
0
5
VUS
0
48
10
0
58
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total051640115

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF250 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients