ZNG1E

Chr 9

Zn regulated GTPase metalloprotein activator 1E

Also known as: CBWD3, CBWD5, DC36

NCBI Gene: 220869 ENSG00000147996 UniProt: Q5RIA9 OMIM: 621672

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GTPase activity; zinc chaperone activity; and zinc ion binding activity. Predicted to be involved in protein maturation. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.95

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.10

OE 1.79 (0.71–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.13 (0.82–1.57)

25 obs / 22.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.79 (0.71–1.95)

0≤0.351.4

Missense OE?1.13 (0.82–1.57)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 4 / 2.2Missense obs/exp: 25 / 22.2Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in ZNG1E?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

79 rare PASS variants

Rare truncating (LoF)

1 in 420

28 rare PASS variants

Rare synonymous (reference)

1 in 420

31 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ZNG1E; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 410	1 in 1,900
South Asian	~43k	1 in 230	1 in 260
Remaining (unassigned)	~30k	1 in 210	1 in 800
European (Finnish)	~27k	1 in 790	1 in 1,500
Admixed American	~22k	1 in 280	1 in 710
African / African American	~21k	1 in 170	1 in 160
East Asian	~20k	1 in 250	1 in 600
Ashkenazi Jewish	~13k	none seen	1 in 1,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 15 coding exons well covered in gnomAD exomes; exons 2, 4, 6, 7, 8 and 3 more poorly covered; exons 12, 15 marginal. Genomes: 4 of 15 (exons 1, 2, 4, 6, 7 and 6 more below).? see exons ↓