ZNF518B

Chr 4

zinc finger protein 518B

This gene encodes a transcription factor that binds DNA and associates with histone methyltransferase complexes to silence gene expression through repressive histone modifications. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.58), but no established disease associations have been reported in humans. Clinical significance of variants in ZNF518B remains to be determined.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.58
LOEUF
DN
Mechanism· predicted
Clinical SummaryZNF518B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 160 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.002
Z-score 3.31
OE 0.34 (0.210.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.92Z-score
OE missense 1.23 (1.161.31)
672 obs / 545.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.34 (0.210.58)
00.351.4
Missense OE1.23 (1.161.31)
00.61.4
Synonymous OE1.30
01.21.6
LoF obs/exp: 10 / 29.4Missense obs/exp: 672 / 545.7Syn Z: -3.38
DN
0.6356th %ile
GOF
0.3590th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

200 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS160
Likely Benign14
15
Pathogenic
1
Likely Pathogenic
160
VUS
14
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
1
0
1
VUS
0
157
3
0
160
Likely Benign
0
13
0
1
14
Benign
0
0
0
0
0
Total0170191190

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF518B · 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

No active trials found for this gene.

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Clinical Literature
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