ZNF618

Chr 9

zinc finger protein 618

ZNF618 encodes a transcriptional coregulator that regulates UHRF2 function as a 5-hydroxymethylcytosine reader by controlling its chromatin localization, and enables transcription coregulator binding activity at pericentric heterochromatin. Loss-of-function mutations cause autosomal recessive neurodevelopmental disorder with severe intellectual disability and variable features. The gene is highly intolerant to loss-of-function variants, with pathogenicity resulting from disrupted epigenetic regulation of gene expression.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.26
Clinical SummaryZNF618
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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.998
Z-score 5.20
OE 0.12 (0.060.26)
Highly constrained

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

Missense Constraint
2.50Z-score
OE missense 0.70 (0.640.76)
379 obs / 543.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.060.26)
00.351.4
Missense OE0.70 (0.640.76)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 5 / 40.8Missense obs/exp: 379 / 543.0Syn Z: 0.00
DN
0.2399th %ile
GOF
0.1999th %ile
LOF
0.80top 5%

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

LOFprediction above median · LOEUF 0.26

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

ZNF618 · 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.

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Clinical Literature
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