ZNF747

Chr 16

zinc finger protein 747

NCBI Gene: 65988 ENSG00000169955 UniProt: Q9BV97

This protein is predicted to bind zinc ions and regulate DNA transcription. Mutations in ZNF747 have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance pattern are not well-established. The gene shows tolerance to loss-of-function variants (pLI 0.07, LOEUF 1.47), suggesting that complete loss of function may not be the primary disease mechanism.

ResearchSummary from RefSeq

Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of DNA-templated transcription. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.47

Clinical Summary— ZNF747

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Population Constraint (gnomAD)

Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

37 VUS of 44 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.47LOEUF

pLI 0.072

Z-score 0.96

OE 0.49 (0.20–1.47)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.24Z-score

OE missense 1.06 (0.92–1.24)

117 obs / 109.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.20–1.47)

0≤0.351.4

Missense OE?1.06 (0.92–1.24)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 2 / 4.1Missense obs/exp: 117 / 109.9Syn Z: -0.45

This gene — mechanism propensity

0.6840th %ile

GOF

0.79top 25%

LOF

0.3648th %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

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	36	37
Likely Benign	0	4	4
Benign	0	0	0
Total	1	40	41

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ZNF747 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →