CPB2

Chr 13

carboxypeptidase B2

Also known as: CPU, PCPB, TAFI

NCBI Gene: 1361 ENSG00000080618 UniProt: Q96IY4

The protein encoded by CPB2 is a carboxypeptidase that cleaves C-terminal arginine and lysine residues from bioactive peptides and downregulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin. Mutations cause carboxypeptidase B2 deficiency, which presents as increased bleeding tendency due to impaired regulation of fibrinolysis, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance.

ResearchSummary from RefSeq, UniProt

Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by trypsin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and its promoter region. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.34

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.16

OE 0.97 (0.71–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.95Z-score

OE missense 0.82 (0.73–0.93)

192 obs / 232.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.71–1.34)

0≤0.351.4

Missense OE?0.82 (0.73–0.93)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 26 / 26.9Missense obs/exp: 192 / 232.9Syn Z: -0.78

Background carrier burden — how many people carry a rare variant somewhere in CPB2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

470 rare PASS variants

Rare truncating (LoF)

1 in 1,200

105 rare PASS variants

Rare synonymous (reference)

1 in 200

202 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPB2. 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 240	1 in 2,300
South Asian	~43k	1 in 100	1 in 320
Remaining (unassigned)	~30k	1 in 160	1 in 910
European (Finnish)	~27k	1 in 490	1 in 5,300
Admixed American	~22k	1 in 190	1 in 400
African / African American	~21k	1 in 160	1 in 410
East Asian	~20k	1 in 150	1 in 880
Ashkenazi Jewish	~13k	1 in 610	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 360	≈ 1 in 710

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): 8 of 11 coding exons well covered in gnomAD exomes; exons 5, 7, 10 marginal. Genomes: 10 of 11 (exon 6 below).? see exons ↓