CPN2

Chr 3

carboxypeptidase N subunit 2

Also known as: ACBP

NCBI Gene: 1370 ENSG00000178772 UniProt: P22792 OMIM: 603104

Predicted to enable enzyme regulator activity. Predicted to be involved in protein stabilization. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.97

Clinical Summary— CPN2

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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

84 VUS of 93 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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?

0.97LOEUF

pLI 0.003

Z-score 1.66

OE 0.49 (0.27–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.29Z-score

OE missense 0.95 (0.86–1.05)

292 obs / 306.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.27–0.97)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 6 / 12.3Missense obs/exp: 292 / 306.5Syn Z: -1.58

This gene — mechanism propensity

0.75top 25%

GOF

0.73top 25%

LOF

0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS84

Likely Benign4

Benign2

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	84	0	84
Likely Benign	4	0	4
Benign	1	1	2
Total	89	1	90

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap CPN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →