CPA5

Summary

CPA5 (carboxypeptidase A5, HGNC:15722) is a protein-coding gene on chromosome 7q32.2, encoding Carboxypeptidase A5 (Q8WXQ8).

Carboxypeptidases have functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Members of the A/B subfamily of carboxypeptidases, such as CPA5, contain an approximately 90-amino acid pro region that assists in the folding of the active carboxypeptidase domain. Cleavage of the pro region activates the enzyme (Wei et al., 2002 [PubMed 11836249]).

Source: NCBI Gene 93979 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_080385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15722
Approved symbol	CPA5
Name	carboxypeptidase A5
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158525
Ensembl biotype	protein_coding
OMIM	609561
Entrez	93979

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000393213, ENST00000431780, ENST00000461828, ENST00000463587, ENST00000466363, ENST00000474905, ENST00000479492, ENST00000485477, ENST00000494311, ENST00000495736, ENST00000497503

RefSeq mRNA: 4 — MANE Select: NM_080385 NM_001127441, NM_001127442, NM_001318223, NM_080385

CCDS: CCDS47713, CCDS5819

Canonical transcript exons

ENST00000474905 — 13 exons

Exon	Start	End
ENSE00001039464	130367372	130367571
ENSE00001270561	130367906	130367990
ENSE00001514509	130345839	130345896
ENSE00001730199	130346393	130346601
ENSE00001858947	130344816	130345205
ENSE00003473504	130349975	130350109
ENSE00003516899	130359589	130359687
ENSE00003543927	130362438	130362539
ENSE00003564089	130347766	130347847
ENSE00003576884	130361143	130361244
ENSE00003589993	130362884	130362994
ENSE00003669604	130363419	130363509
ENSE00003686981	130368410	130368730

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 93.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0297 / max 33.3803, expressed in 5 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81075	0.0262	5
204699	0.0035	2

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.25	gold quality
right testis	UBERON:0004534	89.80	gold quality
left testis	UBERON:0004533	89.32	gold quality
testis	UBERON:0000473	85.62	gold quality
sperm	CL:0000019	85.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.35	gold quality
epithelial cell of pancreas	CL:0000083	65.84	gold quality
tibialis anterior	UBERON:0001385	62.30	silver quality
lymph node	UBERON:0000029	61.12	gold quality
body of pancreas	UBERON:0001150	60.86	gold quality
pituitary gland	UBERON:0000007	60.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.27	gold quality
parotid gland	UBERON:0001831	59.83	gold quality
adenohypophysis	UBERON:0002196	59.59	gold quality
myocardium	UBERON:0002349	58.50	gold quality
pancreas	UBERON:0001264	58.20	gold quality
spleen	UBERON:0002106	57.99	gold quality
ileal mucosa	UBERON:0000331	56.66	silver quality
pancreatic ductal cell	CL:0002079	56.63	silver quality
deltoid	UBERON:0001476	56.10	gold quality
esophagus squamous epithelium	UBERON:0006920	55.98	gold quality
adult organism	UBERON:0007023	55.95	silver quality
islet of Langerhans	UBERON:0000006	55.78	gold quality
cerebellar vermis	UBERON:0004720	55.65	gold quality
quadriceps femoris	UBERON:0001377	55.15	gold quality
mucosa of sigmoid colon	UBERON:0004993	55.08	gold quality
biceps brachii	UBERON:0001507	54.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
right adrenal gland	UBERON:0001233	54.33	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting CPA5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-1226-5P	96.50	65.28	643

Literature-anchored findings (GeneRIF, showing 1)

• mutation screening and imprinting analysis of candidate genes for autism in the 7q12 region. (PMID:11920156)

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cpa5	ENSMUSG00000029788
rattus_norvegicus	Cpa5	ENSRNOG00000010467
drosophila_melanogaster	CG3097	FBGN0029804
drosophila_melanogaster	CG3108	FBGN0029807
drosophila_melanogaster	CG18585	FBGN0031929
drosophila_melanogaster	CG7025	FBGN0031930
drosophila_melanogaster	CG4017	FBGN0032143
drosophila_melanogaster	CG17633	FBGN0032144
drosophila_melanogaster	CG2915	FBGN0033241
drosophila_melanogaster	CG12374	FBGN0033774
drosophila_melanogaster	CG14820	FBGN0035718
drosophila_melanogaster	CG8563	FBGN0035777
drosophila_melanogaster	CG8562	FBGN0035779
drosophila_melanogaster	CG18417	FBGN0035780
drosophila_melanogaster	CG8560	FBGN0035781
drosophila_melanogaster	CG8539	FBGN0035791
drosophila_melanogaster	CG4408	FBGN0039073
drosophila_melanogaster	CG32379	FBGN0052379
drosophila_melanogaster	CG42264	FBGN0259149
caenorhabditis_elegans		WBGENE00004747
caenorhabditis_elegans	T06A4.1	WBGENE00020281
caenorhabditis_elegans	Y47G6A.19	WBGENE00021645
caenorhabditis_elegans		WBGENE00021984

Paralogs (8): CPB2 (ENSG00000080618), CPA1 (ENSG00000091704), CPA4 (ENSG00000128510), CPO (ENSG00000144410), CPB1 (ENSG00000153002), CPA2 (ENSG00000158516), CPA3 (ENSG00000163751), CPA6 (ENSG00000165078)

Protein

Protein identifiers

Carboxypeptidase A5 — Q8WXQ8 (reviewed: Q8WXQ8)

All UniProt accessions (6): A0A1D5RMQ7, A4D1M2, C9JRV5, C9JZE9, Q8WXQ8, H7C4Q6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expression is very low or not detectable.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WXQ8-1	1	yes
Q8WXQ8-2	2
Q8WXQ8-3	3

RefSeq proteins (4): NP_001120913, NP_001120914, NP_001305152, NP_525124* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR003146	M14A_act_pep	Domain
IPR034248	CPA_M14_CPD	Domain
IPR036990	M14A-like_propep	Homologous_superfamily
IPR057246	CARBOXYPEPT_ZN_1	Binding_site
IPR057247	CARBOXYPEPT_ZN_2	Binding_site

Pfam: PF00246, PF02244

UniProt features (24 total): binding site 8, sequence variant 4, splice variant 3, sequence conflict 3, signal peptide 1, propeptide 1, disulfide bond 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXQ8-F1	92.56	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 397 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 323; 324–325; 375; 196–199; 196; 199; 254; 271–272

Disulfide bonds (1): 265–288

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, LHX3_01, chr7q32, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, HOWLIN_CITED1_TARGETS_1_UP, GRYDER_PAX3FOXO1_TOP_ENHANCERS, TAATTA_CHX10_01, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (7): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPA5	AIG1	Q9NVV5	586
CPA5	TSGA13	Q96PP4	546
CPA5	MEST	Q5EB52	536
CPA5	CARF	Q8N187	478
CPA5	LXN	Q9BS40	427
CPA5	CELA1	Q9UNI1	419
CPA5	CIMIP6	Q8N5S3	398
CPA5	SSMEM1	Q8WWF3	370
CPA5	ENPEP	Q07075	362
CPA5	CYP2A7	P20853	328
CPA5	COPG2	Q9UBF2	324
CPA5	CTRB2	Q6GPI1	323
CPA5	LRRC66	Q68CR7	323
CPA5	CLN8	Q9UBY8	319
CPA5	CTRB1	P17538	319

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CPA5	ARVCF	psi-mi:“MI:0914”(association)	0.350
CPA5	RAP1BL	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): CPA5 (Synthetic Growth Defect), POTEE (Affinity Capture-MS), EPHA4 (Affinity Capture-MS), KIRREL (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), CANX (Affinity Capture-MS), NME4 (Affinity Capture-MS), SPG7 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), SVIP (Affinity Capture-MS), ARVCF (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), SEL1L (Affinity Capture-MS), CPA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A075B6S0, A0A075B6Y3, A0A075B6Y9, A0A075B700, A0A075B706, A0A0A0MT70, A0A0A0MT78, A0A0A0MT87, A0A0A0MT89, A0A0A0MT94, A0A0A0MTA4, A0A0A0MTA7, A0A0B4J200, A0A0C4DH62, A0A0J9YWP8, A0A0J9YWX3, A0A0J9YX06, A0A0J9YXA8, A0A0J9YXG5, A0A0J9YXM7, P01206, P0DXA0, P19977, P19978, P19979, P21776, P23002, P28091, P28097, P48794, P55224, P80487, P80539, P80540, P80821, P80981, P81629, P81797, P81954, P83957

Diamond homologs: A1CSU3, A1DGH9, A2QZA2, A6RCF5, A6XGK3, A7EUC0, B0XRS8, B6H233, B6Q972, B6V865, B8M2K0, B8NBP9, B8XGR3, C0NM08, C0SAI5, C1GDH9, C1HE31, C4JEE1, C5FH26, C5FPR9, C5FVN6, C5G6U8, C5JZS0, C5PHW9, C6H4F1, D4AKU7, D4AS12, D4B5N0, D4D675, D4DIW7, D4DL57, E4UPZ6, E5A0U8, E9DD69, O02350, O74818, P00730, P00731, P00732, P04069

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

94 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2126 predictions. Top by Δscore:

Variant	Effect	Δscore
7:130349964:T:TA	acceptor_gain	1.0000
7:130359688:GTA:G	donor_loss	1.0000
7:130361140:CAG:C	acceptor_loss	1.0000
7:130361141:A:AG	acceptor_gain	1.0000
7:130361141:A:C	acceptor_loss	1.0000
7:130361142:G:GA	acceptor_gain	1.0000
7:130361142:GAT:G	acceptor_gain	1.0000
7:130361142:GATA:G	acceptor_gain	1.0000
7:130361142:GATAT:G	acceptor_gain	1.0000
7:130361240:TGAAG:T	donor_loss	1.0000
7:130361241:GAAGG:G	donor_loss	1.0000
7:130361242:AAGG:A	donor_loss	1.0000
7:130361244:GGTAA:G	donor_loss	1.0000
7:130361245:GTAA:G	donor_loss	1.0000
7:130361246:T:A	donor_loss	1.0000
7:130363417:A:AG	acceptor_gain	1.0000
7:130363418:G:GG	acceptor_gain	1.0000
7:130367237:TCA:T	donor_gain	1.0000
7:130367505:C:G	donor_gain	1.0000
7:130367565:G:GT	donor_gain	1.0000
7:130367904:A:AG	acceptor_gain	1.0000
7:130367905:G:GG	acceptor_gain	1.0000
7:130367991:G:GG	donor_gain	1.0000
7:130367995:G:GG	donor_gain	1.0000
7:130368407:TAG:T	acceptor_loss	1.0000
7:130368408:AGATG:A	acceptor_loss	1.0000
7:130368409:GAT:G	acceptor_gain	1.0000
7:130349965:G:A	acceptor_gain	0.9900
7:130359684:GGAG:G	donor_gain	0.9900
7:130359685:GAGG:G	donor_gain	0.9900

AlphaMissense

2884 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:130362501:T:A	W200R	0.992
7:130362501:T:C	W200R	0.992
7:130362503:G:C	W200C	0.990
7:130362503:G:T	W200C	0.990
7:130367503:A:C	S324R	0.989
7:130367505:C:A	S324R	0.989
7:130367505:C:G	S324R	0.989
7:130368502:T:C	F406L	0.988
7:130368504:C:A	F406L	0.988
7:130368504:C:G	F406L	0.988
7:130362971:G:T	G242W	0.987
7:130363503:T:C	F278L	0.986
7:130363505:T:A	F278L	0.986
7:130363505:T:G	F278L	0.986
7:130368479:T:C	L398P	0.982
7:130347780:G:C	R44P	0.980
7:130362964:C:A	N239K	0.980
7:130362964:C:G	N239K	0.980
7:130363432:G:C	R254P	0.977
7:130363436:G:C	K255N	0.976
7:130363436:G:T	K255N	0.976
7:130349984:T:A	W70R	0.975
7:130349984:T:C	W70R	0.975
7:130362496:G:C	R198P	0.974
7:130363478:T:A	D269E	0.974
7:130363478:T:G	D269E	0.974
7:130368484:G:C	D400H	0.974
7:130368535:G:C	A417P	0.974
7:130349986:G:C	W70C	0.973
7:130349986:G:T	W70C	0.973

dbSNP variants (sampled 300 via entrez): RS1000617180 (7:130364056 C>T), RS1000841071 (7:130358969 T>C), RS1001440689 (7:130360611 A>G), RS1001807312 (7:130373025 G>A,C), RS1001891949 (7:130361015 C>T), RS1001900491 (7:130343498 G>A), RS1002136562 (7:130354090 G>C), RS1002153366 (7:130372691 T>C), RS1002167887 (7:130354573 T>C), RS1002520552 (7:130346316 C>G,T), RS1002549611 (7:130371567 A>C,G), RS1002551419 (7:130346526 C>A), RS1002902667 (7:130357164 G>A), RS1003012959 (7:130351253 C>A), RS1003174101 (7:130355974 T>C)

Disease associations

OMIM: gene MIM:609561 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004562_239	Waist circumference adjusted for body mass index	3.000000e-08
GCST004563_177	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-07
GCST004564_71	Waist circumference adjusted for BMI in active individuals	1.000000e-06
GCST005958_14	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-07
GCST005962_34	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST008161_5	Waist circumference adjusted for body mass index	6.000000e-07
GCST90020024_116	A body shape index	8.000000e-10
GCST90020024_117	A body shape index	4.000000e-13
GCST90020026_596	Hip index	3.000000e-14
GCST90020026_597	Hip index	6.000000e-11
GCST90020026_598	Hip index	3.000000e-08
GCST90020026_600	Hip index	2.000000e-16
GCST90020028_276	Hip circumference adjusted for BMI	5.000000e-13
GCST90020028_474	Hip circumference adjusted for BMI	1.000000e-10
GCST90020029_891	Waist circumference adjusted for body mass index	6.000000e-09
GCST90020029_892	Waist circumference adjusted for body mass index	8.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M14: Carboxypeptidase A

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
methyleugenol	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Testosterone	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.