ZNF287

Chr 17

zinc finger protein 287

Also known as: ZKSCAN13, ZSCAN45

NCBI Gene: 57336 ENSG00000141040 UniProt: Q9HBT7

This gene encodes a zinc finger transcription factor involved in transcriptional regulation. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that proper gene dosage is critical for normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the krueppel family of zinc finger proteins, suggesting a role as a transcription factor. Its specific function has not been determined. This gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.40

Clinical Summary— ZNF287

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.

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ClinVar Variants

54 VUS of 65 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.583

Z-score 4.22

OE 0.21 (0.12–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.37Z-score

OE missense 0.67 (0.60–0.74)

268 obs / 402.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.21 (0.12–0.40)

0≤0.351.4

Missense OE?0.67 (0.60–0.74)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 33.3Missense obs/exp: 268 / 402.0Syn Z: 0.52

This gene — mechanism propensity

0.6551th %ile

GOF

0.6443th %ile

LOF

0.4825th %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

65 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	54	54
Likely Benign	5	5
Benign	0	0
Total	59	59

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap ZNF287 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →