ZNG1A

Chr 9

Zn regulated GTPase metalloprotein activator 1A

Also known as: CBWD1, COBP

NCBI Gene: 55871 ENSG00000172785 UniProt: Q9BRT8 OMIM: 611078

ZNG1A encodes a zinc chaperone that transfers zinc cofactor to target metalloproteins, particularly methionine aminopeptidase METAP1 which cleaves initiator methionine from newly synthesized proteins. The gene is highly constrained against loss-of-function variants (pLI ~1.0), but no human disease associations have been established in the provided data. Clinical phenotypes and inheritance patterns associated with ZNG1A mutations are not currently documented.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GTPase activity; zinc chaperone activity; and zinc ion binding activity. Involved in kidney development. 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

1.20

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 1.00

OE 0.72 (0.45–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.00Z-score

OE missense 1.48 (1.32–1.66)

206 obs / 139.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.45–1.20)

0≤0.351.4

Missense OE?1.48 (1.32–1.66)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 11 / 15.2Missense obs/exp: 206 / 139.6Syn Z: -0.87

Background carrier burden — how many people carry a rare variant somewhere in ZNG1A?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

331 rare PASS variants

Rare truncating (LoF)

1 in 850

56 rare PASS variants

Rare synonymous (reference)

1 in 420

93 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNG1A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 400
South Asian	~43k	1 in 100	1 in 3,700
Remaining (unassigned)	~30k	1 in 87	1 in 1,000
European (Finnish)	~27k	1 in 280	≈ 1 in 27,000
Admixed American	~22k	1 in 160	1 in 560
African / African American	~21k	1 in 79	1 in 640
East Asian	~20k	1 in 66	1 in 2,800
Ashkenazi Jewish	~13k	1 in 230	1 in 530
Middle Eastern	~2,876	1 in 210	≈ 1 in 670

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): 7 of 15 coding exons well covered in gnomAD exomes; exons 9, 11 poorly covered; exons 1, 2, 6, 10, 12, 13 marginal. Genomes: 4 of 15 (exons 1, 2, 3, 5, 6 and 6 more below).? see exons ↓