CPVL

Summary

CPVL (carboxypeptidase vitellogenic like, HGNC:14399) is a protein-coding gene on chromosome 7p14.3, encoding Probable serine carboxypeptidase CPVL (Q9H3G5). May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation.

The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined.

Source: NCBI Gene 54504 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_031311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14399
Approved symbol	CPVL
Name	carboxypeptidase vitellogenic like
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106066
Ensembl biotype	protein_coding
OMIM	609780
Entrez	54504

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 39 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000265394, ENST00000396276, ENST00000409850, ENST00000432534, ENST00000437527, ENST00000447426, ENST00000448959, ENST00000449801, ENST00000455544, ENST00000455893, ENST00000458405, ENST00000488891, ENST00000886318, ENST00000886319, ENST00000886320, ENST00000886321, ENST00000886322, ENST00000886323, ENST00000886324, ENST00000886325, ENST00000886326, ENST00000933745, ENST00000933746, ENST00000933747, ENST00000933748, ENST00000933749, ENST00000933750, ENST00000933751, ENST00000933752, ENST00000933753, ENST00000959721, ENST00000959722, ENST00000959723, ENST00000959724, ENST00000959725, ENST00000959726, ENST00000959727, ENST00000959728, ENST00000959729, ENST00000959730

RefSeq mRNA: 17 — MANE Select: NM_031311 NM_001348052, NM_001348054, NM_001371255, NM_001371256, NM_001371257, NM_001371258, NM_001371260, NM_001371261, NM_001371262, NM_001371263, NM_001371264, NM_001371265, NM_001371266, NM_001371267, NM_001371268, NM_019029, NM_031311

CCDS: CCDS5419

Canonical transcript exons

ENST00000265394 — 13 exons

Exon	Start	End
ENSE00000674664	29071773	29071904
ENSE00000674667	29086484	29086550
ENSE00000674669	29092623	29092702
ENSE00000832149	29030577	29030759
ENSE00000832151	29064061	29064234
ENSE00000832153	29066023	29066121
ENSE00000832154	29072301	29072423
ENSE00000832156	29095084	29095142
ENSE00001145183	29146429	29146537
ENSE00001736690	28995235	28995882
ENSE00003533477	29120893	29121071
ENSE00003534965	29112704	29112822
ENSE00003577135	29096103	29096217

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.2453 / max 712.0518, expressed in 998 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83396	24.3049	978
83392	0.3396	75
83394	0.2346	40
83398	0.1742	20
83399	0.1300	36
83395	0.0308	11
83400	0.0236	7
83393	0.0076	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.40	gold quality
mononuclear cell	CL:0000842	99.29	gold quality
leukocyte	CL:0000738	99.25	gold quality
granulocyte	CL:0000094	98.50	gold quality
spleen	UBERON:0002106	97.05	gold quality
renal medulla	UBERON:0000362	96.11	gold quality
metanephros cortex	UBERON:0010533	95.95	gold quality
left lobe of thyroid gland	UBERON:0001120	95.91	gold quality
thyroid gland	UBERON:0002046	95.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.71	gold quality
right lobe of thyroid gland	UBERON:0001119	95.66	gold quality
apex of heart	UBERON:0002098	95.19	gold quality
heart left ventricle	UBERON:0002084	94.79	gold quality
blood	UBERON:0000178	94.62	gold quality
cardiac ventricle	UBERON:0002082	94.61	gold quality
gall bladder	UBERON:0002110	94.46	gold quality
vermiform appendix	UBERON:0001154	94.07	gold quality
lymph node	UBERON:0000029	93.43	gold quality
bone marrow cell	CL:0002092	93.19	gold quality
germinal epithelium of ovary	UBERON:0001304	92.34	gold quality
adult mammalian kidney	UBERON:0000082	92.24	gold quality
bone marrow	UBERON:0002371	92.15	gold quality
calcaneal tendon	UBERON:0003701	91.94	gold quality
heart right ventricle	UBERON:0002080	91.91	gold quality
caecum	UBERON:0001153	91.84	gold quality
colonic epithelium	UBERON:0000397	91.80	gold quality
left ventricle myocardium	UBERON:0006566	91.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.52	gold quality
right coronary artery	UBERON:0001625	91.45	gold quality
omental fat pad	UBERON:0010414	91.00	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5426.60
E-MTAB-7381	yes	3444.47
E-HCAD-24	yes	2323.52
E-GEOD-149689	yes	2319.58
E-CURD-88	yes	1434.48
E-CURD-77	yes	1161.05
E-CURD-55	yes	1005.15
E-HCAD-32	yes	971.45
E-MTAB-10042	yes	931.09
E-MTAB-9221	yes	558.22
E-HCAD-4	yes	73.48
E-HCAD-1	yes	60.45
E-CURD-46	yes	38.94
E-MTAB-10553	yes	35.74
E-MTAB-6701	yes	26.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting CPVL, 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-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-561-5P	98.25	68.13	1365

Literature-anchored findings (GeneRIF, showing 2)

• genetic association studies in a Chinese population with type 2 diabetes: An SNP in CPVL (rs39059) is associated with diabetic retinopathy in a Chinese population of type 2 diabetic patients. (PMID:21911749)
• CPVL suppresses metastasis of nasopharyngeal carcinoma through inhibiting epithelial-mesenchymal transition. (PMID:37712963)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpvl	ENSDARG00000056480
mus_musculus	Cpvl	ENSMUSG00000052955
rattus_norvegicus	Cpvl	ENSRNOG00000009172
drosophila_melanogaster	CG4572	FBGN0038738

Paralogs (2): CTSA (ENSG00000064601), SCPEP1 (ENSG00000121064)

Protein

Protein identifiers

Probable serine carboxypeptidase CPVL — Q9H3G5 (reviewed: Q9H3G5)

Alternative names: Carboxypeptidase, vitellogenic-like, Vitellogenic carboxypeptidase-like protein

All UniProt accessions (8): Q9H3G5, C9J6L4, C9JI22, C9JLV0, C9JVI2, C9JZ94, H7C0X5, H7C218

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation.

Tissue specificity. Expressed in macrophages but not in other leukocytes. Abundantly expressed in heart and kidney. Also expressed in spleen, leukocytes, and placenta.

Similarity. Belongs to the peptidase S10 family.

RefSeq proteins (17): NP_001334981, NP_001334983, NP_001358184, NP_001358185, NP_001358186, NP_001358187, NP_001358189, NP_001358190, NP_001358191, NP_001358192, NP_001358193, NP_001358194, NP_001358195, NP_001358196, NP_001358197, NP_061902, NP_112601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001563	Peptidase_S10	Family
IPR018202	Ser_caboxypep_ser_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00450

UniProt features (18 total): sequence variant 4, sequence conflict 4, glycosylation site 4, active site 3, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3G5-F1	93.55	0.89

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 (3): 204; 388; 448

Glycosylation sites (4): 81, 132, 307, 346

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, MCLACHLAN_DENTAL_CARIES_UP, MODULE_45, SHEPARD_BMYB_MORPHOLINO_DN, GNF2_CD1D, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, GNF2_S100A4, MODULE_171, BASSO_HAIRY_CELL_LEUKEMIA_UP, GNF2_HCK, ACEVEDO_LIVER_CANCER_UP, NOUZOVA_METHYLATED_IN_APL

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

GO Molecular Function (4): serine-type carboxypeptidase activity (GO:0004185), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
carboxypeptidase activity	1
serine-type exopeptidase activity	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
extracellular vesicle	1

Protein interactions and networks

STRING

2452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPVL	A0A2R8YEI5	A0A2R8YEI5	692
CPVL	FRMD3	A2A2Y4	668
CPVL	CHN2	P52757	651
CPVL	CCDC180	Q9P1Z9	604
CPVL	CNDP1	Q96KN2	502
CPVL	UBAC2	Q8NBM4	482
CPVL	AIF1L	Q9BQI0	460
CPVL	CPA3	P15088	443
CPVL	ACBD3	Q9H3P7	443
CPVL	LY86	O95711	441
CPVL	KCNJ5	P48544	440
CPVL	CACNA2D1	P54289	422
CPVL	UBASH3B	Q8TF42	416
CPVL	LPAR6	P43657	415
CPVL	DPPA4	Q7L190	402

IntAct

151 interactions, top by confidence:

A	B	Type	Score
SEPTIN2	SEPTIN6	psi-mi:“MI:0914”(association)	0.950
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
BRAF	NRAS	psi-mi:“MI:0914”(association)	0.860
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
PPP1R18	PPP1CA	psi-mi:“MI:0914”(association)	0.810
SEPTIN9	SEPTIN6	psi-mi:“MI:0914”(association)	0.800
YAP1	MPDZ	psi-mi:“MI:0914”(association)	0.780
E6	TAX1BP3	psi-mi:“MI:0914”(association)	0.650
LETMD1	RTN4IP1	psi-mi:“MI:0914”(association)	0.640
SEPTIN11	SEPTIN6	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
DCTN5	DCTN6	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
SS18L2	SMARCA2	psi-mi:“MI:0914”(association)	0.570
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
GRK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
DCTN6	DCTN3	psi-mi:“MI:0914”(association)	0.530
ACTR1A	DCTN3	psi-mi:“MI:0914”(association)	0.530
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
L3MBTL3	P4HA1	psi-mi:“MI:0914”(association)	0.530
E6	CASK	psi-mi:“MI:0914”(association)	0.520
E6	TAX1BP3	psi-mi:“MI:0914”(association)	0.520
Tax	TAX1BP3	psi-mi:“MI:0914”(association)	0.520
NUCB1	NUCB2	psi-mi:“MI:0914”(association)	0.500
Lats2	MPDZ	psi-mi:“MI:0914”(association)	0.420

BioGRID (704): CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CPVL (Affinity Capture-MS), CYB5R3 (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), QSOX2 (Affinity Capture-MS), OCIAD1 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), MANEA (Affinity Capture-MS), MICU1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKK5, A3QVN2, A3QVN3, A3QVN4, A3QVN5, A3QVN6, A3QVN9, A3QVP0, A7YWG4, C3YWU0, J3S820, O65355, P04066, P06865, P14384, P17164, P29416, P31428, P31430, P48300, P58780, P93164, Q05A56, Q0V8R6, Q2KIM0, Q2M3T9, Q2VQV9, Q4QR71, Q5RC46, Q5RC84, Q5RFD6, Q5RFE4, Q60HF8, Q62867, Q63108, Q641X3, Q6AXR4, Q6AYS4, Q80V42, Q8R0W5

Diamond homologs: A0A0C3VJP4, A0A1L9WN42, A1CUJ5, A1DP75, A4RPY8, A5AB21, A5YCB8, A6RGA0, A6RUD7, A7F4H5, B2WKF1, B6HPP6, B6QAN5, B8M044, B8XGR4, C0NX46, C0SGX7, C1GG77, C1GXD8, C4YTG0, C5FWJ1, C5GEU5, C5K1Y9, C5P212, C7YQJ2, C9WMM5, D1ZG13, D4ANB6, D4AQA7, D4ASE6, D4AZ71, D4B0Q6, D4DLI1, E4USS9, E5A7I6, E7R7R2, O04084, O64810, O64811, O81009

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	11	14.8×	7e-08
COPI-independent Golgi-to-ER retrograde traffic	10	14.4×	4e-07
MHC class II antigen presentation	16	9.9×	4e-09
Loss of Nlp from mitotic centrosomes	9	9.9×	3e-05
Loss of proteins required for interphase microtubule organization from the centrosome	9	9.9×	3e-05
AURKA Activation by TPX2	9	9.5×	4e-05
Anchoring of the basal body to the plasma membrane	12	9.4×	1e-06
Regulation of PLK1 Activity at G2/M Transition	10	8.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoskeleton-dependent cytokinesis	7	29.9×	2e-06
protein autophosphorylation	11	8.5×	5e-05
intracellular protein localization	11	6.1×	6e-04
protein phosphorylation	14	5.1×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2675 predictions. Top by Δscore:

Variant	Effect	Δscore
7:29030572:CCTA:C	donor_loss	1.0000
7:29030574:TA:T	donor_loss	1.0000
7:29030575:A:AT	donor_loss	1.0000
7:29030755:AGAAC:A	acceptor_gain	1.0000
7:29030756:GAAC:G	acceptor_gain	1.0000
7:29030757:AACCT:A	acceptor_loss	1.0000
7:29030758:AC:A	acceptor_gain	1.0000
7:29030759:CC:C	acceptor_gain	1.0000
7:29030760:C:CC	acceptor_gain	1.0000
7:29030761:T:C	acceptor_loss	1.0000
7:29030765:A:AC	acceptor_gain	1.0000
7:29066056:T:TA	donor_gain	1.0000
7:29071765:GAACT:G	donor_loss	1.0000
7:29071766:AACT:A	donor_loss	1.0000
7:29071767:ACTCA:A	donor_loss	1.0000
7:29071768:CTCAC:C	donor_loss	1.0000
7:29071769:TCA:T	donor_loss	1.0000
7:29071770:CA:C	donor_loss	1.0000
7:29071771:A:AC	donor_gain	1.0000
7:29071771:A:C	donor_loss	1.0000
7:29071772:C:CG	donor_gain	1.0000
7:29071772:CT:C	donor_gain	1.0000
7:29071772:CTT:C	donor_gain	1.0000
7:29071799:T:TA	donor_gain	1.0000
7:29071905:C:CC	acceptor_gain	1.0000
7:29072299:A:AC	donor_gain	1.0000
7:29072300:C:CC	donor_gain	1.0000
7:29072300:CTGA:C	donor_gain	1.0000
7:29092617:TTTTA:T	donor_loss	1.0000
7:29092618:TTTAC:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015142 (7:29175232 T>C), RS1000029828 (7:29133734 C>A), RS1000044601 (7:29111656 C>G,T), RS1000068472 (7:29190550 A>C), RS1000153231 (7:29010056 G>A), RS1000185048 (7:29171175 A>G), RS1000224940 (7:29164533 C>A,T), RS1000228892 (7:29151967 A>G), RS1000232343 (7:29123829 G>A), RS1000262586 (7:29059426 T>C), RS1000319747 (7:29188024 A>G), RS1000322980 (7:29145389 T>A), RS1000334177 (7:29145177 T>C), RS1000347361 (7:29004293 G>A), RS1000349982 (7:29023286 C>G,T)

Disease associations

OMIM: gene MIM:609780 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000077_3	Diabetes related insulin traits	8.000000e-06
GCST000477_20	Cognitive performance	5.000000e-06
GCST002211_1	Psychosis (atypical)	2.000000e-07
GCST004785_1	Vitiligo	9.000000e-26
GCST005896_74	Non-melanoma skin cancer	3.000000e-09
GCST006106_6	Forehead morphology	4.000000e-06
GCST006465_19	Endometrial cancer (endometrioid histology)	2.000000e-08
GCST008870_60	Keratinocyte cancer (MTAG)	2.000000e-19
GCST008871_54	Basal cell carcinoma	1.000000e-19
GCST90013410_4	Basal cell carcinoma	5.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004541	HbA1c measurement
EFO:0003926	neuropsychological test
EFO:0009260	non-melanoma skin carcinoma
EFO:0010176	keratinocyte carcinoma

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 — S10: Carboxypeptidase Y

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	10
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
bisphenol A	increases methylation, decreases expression, increases expression, affects expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
vanadyl sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
MRK 003	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1

Clinical trials (associated diseases)

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