ZSCAN20

Chr 1

zinc finger and SCAN domain containing 20

Also known as: KOX29, ZFP-31, ZNF31, ZNF360

NCBI Gene: 7579 ENSG00000121903 UniProt: P17040

The protein is predicted to function as a DNA-binding transcription factor that regulates RNA polymerase II-mediated transcription in the nucleus. This gene is highly constrained against loss-of-function variants (LOEUF 0.51), but no definitive human disease associations have been established for ZSCAN20 mutations in the current medical literature.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.51

Clinical Summary— ZSCAN20

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

127 VUS of 141 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.000

Z-score 4.08

OE 0.33 (0.21–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.34Z-score

OE missense 0.84 (0.78–0.91)

486 obs / 576.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.21–0.51)

0≤0.351.4

Missense OE?0.84 (0.78–0.91)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 42.9Missense obs/exp: 486 / 576.2Syn Z: 0.42

This gene — mechanism propensity

0.77top 25%

GOF

0.72top 25%

LOF

0.2774th %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

141 submitted variants in ClinVar

ClinVar

Classification Summary

VUS127

Likely Benign6

127

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	127	127
Likely Benign	6	6
Benign	0	0
Total	133	133

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap ZSCAN20 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →