CPA3

Chr 3

carboxypeptidase A3

Also known as: MC-CPA

NCBI Gene: 1359 ENSG00000163751 UniProt: P15088 OMIM: 114851

This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. The encoded preproprotein is proteolytically processed to generate a mature protease that is released by mast cells and may be involved in the degradation of endogenous proteins and the inactivation of venom-associated peptides. Expression of this gene may be elevated in human asthma patients. [provided by RefSeq, Nov 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.32

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.27

OE 0.94 (0.69–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.69Z-score

OE missense 1.13 (1.02–1.25)

259 obs / 229.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.94 (0.69–1.32)

0≤0.351.4

Missense OE?1.13 (1.02–1.25)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 25 / 26.5Missense obs/exp: 259 / 229.4Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in CPA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

590 rare PASS variants

Rare truncating (LoF)

1 in 1,000

82 rare PASS variants

Rare synonymous (reference)

1 in 230

186 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPA3. 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 84	1 in 1,400
South Asian	~43k	1 in 54	1 in 580
Remaining (unassigned)	~30k	1 in 100	1 in 1,000
European (Finnish)	~27k	1 in 340	≈ 1 in 8,900
Admixed American	~22k	1 in 63	1 in 920
African / African American	~21k	1 in 83	1 in 1,000
East Asian	~20k	1 in 120	1 in 2,200
Ashkenazi Jewish	~13k	1 in 500	1 in 1,500
Middle Eastern	~2,884	1 in 110	1 in 480

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): 10 of 11 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 11.? see exons ↓