ZNG1E

Chr 9

Zn regulated GTPase metalloprotein activator 1E

Also known as: CBWD3, CBWD5, DC36

This protein functions as a zinc chaperone that transfers zinc cofactors to target metalloproteins, specifically catalyzing zinc insertion into methionine aminopeptidase METAP1 to activate protein maturation processes. The gene is not highly constrained against loss-of-function variants, suggesting that haploinsufficiency may not be the primary disease mechanism. No well-established disease associations have been reported for mutations in this gene.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.95
Clinical SummaryZNG1E
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -1.10
OE 1.79 (0.711.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.13 (0.821.57)
25 obs / 22.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.79 (0.711.95)
00.351.4
Missense OE1.13 (0.821.57)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 2.2Missense obs/exp: 25 / 22.2Syn Z: 0.24
DN
0.7130th %ile
GOF
0.6345th %ile
LOF
0.2874th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNG1E · 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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No publications found for ZNG1E