AMZ1

Chr 7

archaelysin family metallopeptidase 1

NCBI Gene: 155185 ENSG00000174945 UniProt: Q400G9 OMIM: 615168

The protein is a probable zinc metalloprotease that cleaves other proteins through proteolysis. Mutations in this gene have not been definitively associated with any recognized human disease or inheritance pattern. This gene shows low constraint against loss-of-function variants, suggesting it may be more tolerant to disruption than highly constrained genes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.94

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -2.36

OE 1.61 (1.17–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.59Z-score

OE missense 1.58 (1.46–1.70)

485 obs / 307.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.61 (1.17–1.94)

0≤0.351.4

Missense OE?1.58 (1.46–1.70)

0≤0.61.4

Synonymous OE?1.50

0≤1.21.6

LoF obs/exp: 28 / 17.4Missense obs/exp: 485 / 307.8Syn Z: -4.68

Background carrier burden — how many people carry a rare variant somewhere in AMZ1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 29

1,194 rare PASS variants

Rare truncating (LoF)

1 in 300

193 rare PASS variants

Rare synonymous (reference)

1 in 59

393 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AMZ1. 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 37	1 in 480
South Asian	~43k	1 in 28	1 in 310
Remaining (unassigned)	~30k	1 in 26	1 in 420
European (Finnish)	~26k	1 in 76	1 in 870
Admixed American	~22k	1 in 26	1 in 470
African / African American	~21k	1 in 34	1 in 210
East Asian	~20k	1 in 26	1 in 360
Ashkenazi Jewish	~13k	1 in 110	1 in 2,000
Middle Eastern	~2,884	1 in 26	1 in 280

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓