ZNF669

Chr 1

zinc finger protein 669

NCBI Gene: 79862ENSG00000188295UniProt: Q96BR6

The protein functions as a DNA-binding transcription factor that regulates RNA polymerase II transcription in the nucleus. Currently, no established human diseases have been definitively linked to ZNF669 mutations, and the inheritance pattern remains unknown. The gene shows tolerance to loss-of-function variants in population studies, suggesting that haploinsufficiency may not be pathogenic.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.46
Clinical Summary— ZNF669
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 86 VUS of 170 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.46LOEUF
pLI 0.001
Z-score 0.74
OE 0.70 (0.36–1.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.67Z-score
OE missense 1.12 (1.01–1.23)
283 obs / 253.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.36–1.46)
0≤0.351.4
Missense OE1.12 (1.01–1.23)
0≤0.61.4
Synonymous OE1.19
0≤1.21.6
LoF obs/exp: 5 / 7.1Missense obs/exp: 283 / 253.0Syn Z: -1.45
DN
0.75top 25%
GOF
0.79top 25%
LOF
0.3259th %ile

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

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.

ClinVar Variant Classifications

170 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic6
VUS86
Likely Benign6
Benign1
66
Pathogenic
6
Likely Pathogenic
86
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
66
0
66
Likely Pathogenic
0
0
6
0
6
VUS
0
72
14
0
86
Likely Benign
0
2
4
0
6
Benign
0
0
1
0
1
Total074910165

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF669 · 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

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
Specific genetic aberrations of parathyroid in Chinese patients with tertiary hyperparathyroidism using whole-exome sequencing
Li L et al.·Front Endocrinol (Lausanne)
2023Cohort
Characterization of progression-related alternative splicing events in testicular germ cell tumors
Zhang CJ et al.·Asian J Androl
2021
Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma
Takigawa H et al.·Cancers (Basel)
2023
Bioinformatics analyses of the pathogenesis and new biomarkers of chronic obstructive pulmonary disease
Zhang J et al.·Medicine (Baltimore)
2021
Targeting YBX1-m5C mediates RNF115 mRNA circularisation and translation to enhance vulnerability of ferroptosis in hepatocellular carcinoma
Li O et al.·Clin Transl Med
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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