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…

DNmechanismLOEUF 1.32

Clinical Summary— CPA3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

59 VUS of 71 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.6550th %ile

GOF

0.5268th %ile

LOF

0.3357th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

71 submitted variants in ClinVar

ClinVar

Classification Summary

VUS59

Likely Benign3

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	59	0	59
Likely Benign	2	1	3
Benign	2	1	3
Total	63	2	65

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap CPA3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →