ZNF397

Chr 18

zinc finger protein 397

Also known as: ZNF47, ZSCAN15

NCBI Gene: 84307ENSG00000186812UniProt: Q8NF99

This gene encodes a transcriptional repressor containing a SCAN domain and zinc finger repeats that localizes to centromeres during cell division. Mutations in ZNF397 cause autosomal dominant neurodevelopmental disorder with epilepsy and hypotonia. The gene is not highly constrained against loss-of-function variants, suggesting the pathogenic variants may act through other mechanisms.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
0.80
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ZNF397
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 103 VUS of 160 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
0.80LOEUF
pLI 0.000
Z-score 2.27
OE 0.49 (0.30–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.03Z-score
OE missense 0.82 (0.74–0.92)
222 obs / 269.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.30–0.80)
0≤0.351.4
Missense OE0.82 (0.74–0.92)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 11 / 22.6Missense obs/exp: 222 / 269.4Syn Z: 0.63
DN
0.78top 25%
GOF
0.6832th %ile
LOF
0.2968th %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

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic3
VUS103
Likely Benign4
40
Pathogenic
3
Likely Pathogenic
103
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
3
0
3
VUS
0
102
1
0
103
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total0105450150

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF397 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients