ZNF654

Chr 3

zinc finger protein 654

ZNF654 encodes a transcription factor that binds DNA and regulates gene transcription by RNA polymerase II in the nucleus. Mutations cause autosomal dominant intellectual disability with seizures, and the gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.17), indicating that even single functional copies are critical for normal development.

ResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical SummaryZNF654
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 0.998
Z-score 3.89
OE 0.00 (0.000.17)
Highly constrained

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

Missense Constraint
1.13Z-score
OE missense 0.82 (0.730.91)
245 obs / 300.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.17)
00.351.4
Missense OE0.82 (0.730.91)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 0 / 17.6Missense obs/exp: 245 / 300.1Syn Z: 0.73
DN
0.2598th %ile
GOF
0.3392th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF654 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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

No open access results found