ZNF337

Chr 20

zinc finger protein 337

This gene encodes a zinc finger protein that may be involved in transcriptional regulation, though its specific function remains undetermined. The gene shows low constraint against loss-of-function variants (pLI 0.004, LOEUF 1.617), suggesting tolerance to protein-disrupting mutations. No established disease associations have been reported for ZNF337 mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
18
P/LP submissions
0%
P/LP missense
1.62
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryZNF337
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 129 VUS of 153 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.62LOEUF
pLI 0.004
Z-score 0.54
OE 0.75 (0.361.62)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.45Z-score
OE missense 1.06 (0.981.15)
418 obs / 392.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.75 (0.361.62)
00.351.4
Missense OE1.06 (0.981.15)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 4 / 5.4Missense obs/exp: 418 / 392.8Syn Z: -0.76
DN
0.75top 25%
GOF
0.7028th %ile
LOF
0.3067th %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

153 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic3
VUS129
Likely Benign2
15
Pathogenic
3
Likely Pathogenic
129
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
3
0
3
VUS
0
124
5
0
129
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total0125240149

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF337 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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