ZNF689

Chr 16

zinc finger protein 689

Also known as: TIPUH1

The ZNF689 protein binds histones and regulates transcription by RNA polymerase II. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy or early childhood. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.5), suggesting some intolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.50
Clinical SummaryZNF689
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.418
Z-score 3.10
OE 0.22 (0.110.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.52Z-score
OE missense 0.62 (0.560.69)
218 obs / 351.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.110.50)
00.351.4
Missense OE0.62 (0.560.69)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 18.3Missense obs/exp: 218 / 351.1Syn Z: 0.97
DN
0.6065th %ile
GOF
0.6442th %ile
LOF
0.4038th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

ZNF689 · 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
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗