ZSCAN30

Chr 18

zinc finger and SCAN domain containing 30

Also known as: ZNF-WYM, ZNF397OS, ZNF917

NCBI Gene: 100101467 ENSG00000186814 UniProt: Q86W11

The protein functions as a DNA-binding transcription factor that regulates gene expression by RNA polymerase II in the nucleus. Mutations in this gene cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities. The gene shows very low constraint against loss-of-function variants, suggesting tolerance to such mutations.

Summary from RefSeq, UniProt

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.43

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— ZSCAN30

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

43 unique Pathogenic / Likely Pathogenic· 68 VUS of 122 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

1.43LOEUF

pLI 0.000

Z-score 0.11

OE 0.97 (0.68–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

0.07Z-score

OE missense 0.99 (0.89–1.09)

256 obs / 259.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.97 (0.68–1.43)

0≤0.351.4

Missense OE0.99 (0.89–1.09)

0≤0.61.4

Synonymous OE0.87

0≤1.21.6

LoF obs/exp: 19 / 19.5Missense obs/exp: 256 / 259.3Syn Z: 0.99

0.78top 25%

GOF

0.7028th %ile

LOF

0.3357th %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.