ZNF717

Chr 3

zinc finger protein 717

Also known as: OB1, X17, ZNF838

NCBI Gene: 100131827 ENSG00000227124 UniProt: Q9BY31 OMIM: 618405

The protein is a KRAB zinc-finger transcriptional regulator that binds nucleic acids and controls cellular functions including proliferation, differentiation, and apoptosis. Mutations cause neurodevelopmental disorder with epilepsy, which follows an autosomal dominant inheritance pattern. The gene shows low constraint against loss-of-function variants, suggesting the disorder may not result from simple protein loss.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a Kruppel-associated box (KRAB) zinc-finger protein, which belongs to a large group of transcriptional regulators in mammals. These proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation and apoptosis, and in regulating viral replication and transcription. A pseudogene of this gene was identified on chromosome 1. [provided by RefSeq, May 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.91

Clinical Summary— ZNF717

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 VUS of 13 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?

1.91LOEUF

pLI 0.019

Z-score -0.35

OE 1.30 (0.43–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.91Z-score

OE missense 1.48 (1.31–1.67)

186 obs / 125.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.30 (0.43–1.91)

0≤0.351.4

Missense OE?1.48 (1.31–1.67)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 2 / 1.5Missense obs/exp: 186 / 125.8Syn Z: -2.88

This gene — mechanism propensity

0.90top 5%

GOF

0.86top 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

13 submitted variants in ClinVar

ClinVar

Classification Summary

VUS2

Likely Benign7

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	2	0	0	2
Likely Benign	1	1	5	7
Benign	1	0	1	2
Total	4	1	6	11

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap ZNF717 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →