CPXM2

Summary

CPXM2 (carboxypeptidase X, M14 family member 2, HGNC:26977) is a protein-coding gene on chromosome 10q26.13, encoding Inactive carboxypeptidase-like protein X2 (Q8N436). May be involved in cell-cell interactions.

Predicted to enable metallocarboxypeptidase activity and zinc ion binding activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region.

Source: NCBI Gene 119587 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 169 total
• MANE Select transcript: NM_198148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26977
Approved symbol	CPXM2
Name	carboxypeptidase X, M14 family member 2
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	UNQ676, CPX2
Ensembl gene	ENSG00000121898
Ensembl biotype	protein_coding
OMIM	617348
Entrez	119587

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000241305, ENST00000368854, ENST00000481775, ENST00000615851, ENST00000909347, ENST00000909348, ENST00000909349, ENST00000909350

RefSeq mRNA: 1 — MANE Select: NM_198148 NM_198148

CCDS: CCDS7637

Canonical transcript exons

ENST00000241305 — 14 exons

Exon	Start	End
ENSE00001251250	123745639	123747017
ENSE00001772866	123768526	123768722
ENSE00001870412	123891356	123891807
ENSE00003464101	123761872	123762169
ENSE00003474799	123797976	123798126
ENSE00003507650	123880211	123880309
ENSE00003536039	123799115	123799199
ENSE00003554551	123780167	123780255
ENSE00003572896	123766973	123767152
ENSE00003583394	123757213	123757352
ENSE00003653243	123862614	123862723
ENSE00003663070	123770916	123771039
ENSE00003683139	123842349	123842488
ENSE00003688522	123754663	123754762

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 98.31.

FANTOM5 (CAGE): breadth broad, TPM avg 7.7595 / max 360.8522, expressed in 709 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111781	7.7460	709
111780	0.0135	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	98.31	gold quality
ascending aorta	UBERON:0001496	98.30	gold quality
thoracic aorta	UBERON:0001515	98.29	gold quality
descending thoracic aorta	UBERON:0002345	98.21	gold quality
saphenous vein	UBERON:0007318	98.12	gold quality
vena cava	UBERON:0004087	97.01	gold quality
pericardium	UBERON:0002407	96.66	gold quality
trigeminal ganglion	UBERON:0001675	96.54	gold quality
coronary artery	UBERON:0001621	96.20	gold quality
left coronary artery	UBERON:0001626	95.91	gold quality
aorta	UBERON:0000947	95.74	gold quality
urethra	UBERON:0000057	94.81	gold quality
trachea	UBERON:0003126	94.63	gold quality
dorsal root ganglion	UBERON:0000044	94.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.19	gold quality
lower esophagus	UBERON:0013473	94.07	gold quality
corpus epididymis	UBERON:0004359	94.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.98	gold quality
popliteal artery	UBERON:0002250	93.84	gold quality
tibial artery	UBERON:0007610	93.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.54	gold quality
smooth muscle tissue	UBERON:0001135	93.13	gold quality
tibial nerve	UBERON:0001323	90.91	gold quality
superficial temporal artery	UBERON:0001614	90.61	gold quality
mucosa of stomach	UBERON:0001199	90.37	gold quality
pigmented layer of retina	UBERON:0001782	90.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.47	silver quality
calcaneal tendon	UBERON:0003701	89.43	gold quality
tibia	UBERON:0000979	89.34	gold quality
cartilage tissue	UBERON:0002418	89.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting CPXM2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6510-5P	99.14	66.59	1081

Literature-anchored findings (GeneRIF, showing 5)

• Performance metrics were used to select SNPs in stage 1, which were then genotyped to another dataset (stage 2). Four SNPs (CPXM2 rs2362967, APOC1 rs4420638, ZNF521 rs7230380, and rs12965520) were identified for LOAD by both traditional P-values (without correcting for multiple tests) and performance metrics. (PMID:27805002)
• The Genetic variants located in CPXM2 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. (PMID:30217166)
• Results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in GCs. (PMID:31364750)
• imply an active role for Carboxypeptidase X, M14 family member 2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in osteosarcoma (PMID:31651348)
• Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension. (PMID:34916661)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000117193
mus_musculus	Cpxm2	ENSMUSG00000030862
rattus_norvegicus	Cpxm2	ENSRNOG00000015902

Paralogs (7): CPXM1 (ENSG00000088882), AEBP1 (ENSG00000106624), CPD (ENSG00000108582), CPE (ENSG00000109472), CPZ (ENSG00000109625), CPN1 (ENSG00000120054), CPM (ENSG00000135678)

Protein

Protein identifiers

Inactive carboxypeptidase-like protein X2 — Q8N436 (reviewed: Q8N436)

All UniProt accessions (2): Q49AT5, Q8N436

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell-cell interactions.

Subcellular location. Secreted.

Similarity. Belongs to the peptidase M14 family.

RefSeq proteins (1): NP_937791* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000834	Peptidase_M14	Domain
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR050753	Peptidase_M14_domain	Family
IPR057246	CARBOXYPEPT_ZN_1	Binding_site

Pfam: PF00246, PF00754, PF13620

UniProt features (15 total): glycosylation site 5, compositionally biased region 3, domain 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N436-F1	82.58	0.67

Functional residue map

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

Disulfide bonds (1): 136–293

Glycosylation sites (5): 281, 337, 491, 231, 241

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, LINDVALL_IMMORTALIZED_BY_TERT_DN, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, COWLING_MYCN_TARGETS, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY, GSE13522_WT_VS_IFNG_KO_SKIN_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A

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

GO Molecular Function (2): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270)

GO Cellular Component (1): 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
cellular anatomical structure	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPXM2	AGTPBP1	Q9UPW5	668
CPXM2	AGBL4	Q5VU57	634
CPXM2	TTL	Q8NG68	541
CPXM2	TTLL4	Q14679	530
CPXM2	TTLL7	Q6ZT98	505
CPXM2	TTLL1	O95922	474
CPXM2	FAM13C	Q8NE31	452
CPXM2	TECTB	Q96PL2	442
CPXM2	GPR26	Q8NDV2	437
CPXM2	TMEM201	Q5SNT2	394
CPXM2	FHIP1A	Q05DH4	380
CPXM2	OVCH2	Q7RTZ1	374
CPXM2	TSEN15	Q8WW01	370
CPXM2	AGBL1	Q96MI9	363
CPXM2	BRINP1	O60477	358
CPXM2	TMEM74B	Q9NUR3	358

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CPXM2	EDRF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): TRIM68 (Affinity Capture-MS), EDRF1 (Affinity Capture-MS), CPXM2 (Affinity Capture-MS)

ESM2 similar proteins: A2RUV9, F8W3R9, O18738, O43278, O54858, O88393, O97827, P00734, P00735, P0C5J5, P12259, P18292, P26342, P35054, P51511, Q08629, Q08E66, Q09101, Q14118, Q24567, Q24568, Q28685, Q29243, Q5R537, Q5RD69, Q62165, Q62288, Q640N1, Q66K79, Q701R2, Q7TQN3, Q80TS3, Q8BKV0, Q8IUX7, Q8N436, Q8R4V4, Q8TEU8, Q91ZV2, Q91ZV3, Q92563

Diamond homologs: A2RUV9, A5A6K7, O14786, O17754, O18806, O35276, O35375, O35474, O43854, O54858, O54991, O60462, O75976, O88783, O89001, P00451, P02886, P02887, P02888, P04836, P12259, P12263, P14384, P15087, P15169, P16870, P21956, P28824, P29068, P37892, P39041, P42787, P70490, P78357, P79385, P79795, P83852, P97333, P97846, P98092

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3139 predictions. Top by Δscore:

Variant	Effect	Δscore
10:123761870:A:AC	donor_gain	1.0000
10:123761870:ACTT:A	donor_gain	1.0000
10:123761871:C:CC	donor_gain	1.0000
10:123761871:CTTC:C	donor_gain	1.0000
10:123761873:T:TA	donor_gain	1.0000
10:123761874:C:A	donor_gain	1.0000
10:123761916:T:TA	donor_gain	1.0000
10:123766967:ACTCA:A	donor_loss	1.0000
10:123766968:CTCAC:C	donor_loss	1.0000
10:123766969:TCACC:T	donor_loss	1.0000
10:123766970:CACCG:C	donor_loss	1.0000
10:123766971:A:C	donor_loss	1.0000
10:123766972:C:A	donor_loss	1.0000
10:123767029:T:TA	donor_gain	1.0000
10:123768524:ACC:A	donor_gain	1.0000
10:123768525:CCC:C	donor_gain	1.0000
10:123768534:AGG:A	donor_gain	1.0000
10:123768725:T:TC	acceptor_gain	1.0000
10:123768730:C:CT	acceptor_gain	1.0000
10:123798138:C:CT	acceptor_gain	1.0000
10:123798139:A:C	acceptor_gain	1.0000
10:123799107:AGACT:A	donor_loss	1.0000
10:123799108:GACTC:G	donor_loss	1.0000
10:123799109:ACTC:A	donor_loss	1.0000
10:123799110:CTCA:C	donor_loss	1.0000
10:123799111:TCAC:T	donor_loss	1.0000
10:123799112:CACC:C	donor_loss	1.0000
10:123799113:A:AC	donor_gain	1.0000
10:123799113:ACCA:A	donor_loss	1.0000
10:123799114:C:CC	donor_gain	1.0000

AlphaMissense

4975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:123746996:C:G	R680P	0.999
10:123757252:C:A	W626C	0.999
10:123757252:C:G	W626C	0.999
10:123757254:A:G	W626R	0.999
10:123757254:A:T	W626R	0.999
10:123757292:C:G	C613S	0.999
10:123757292:C:T	C613Y	0.999
10:123757293:A:T	C613S	0.999
10:123798010:G:C	C285W	0.999
10:123798050:C:G	R272P	0.999
10:123799163:G:C	S230R	0.999
10:123799163:G:T	S230R	0.999
10:123799164:C:A	S230I	0.999
10:123799165:T:G	S230R	0.999
10:123842452:A:G	W184R	0.999
10:123842452:A:T	W184R	0.999
10:123862633:C:G	R165P	0.999
10:123746969:A:T	V689D	0.998
10:123746990:A:G	L682P	0.998
10:123747003:A:C	Y678D	0.998
10:123754752:C:T	G643D	0.998
10:123754753:C:G	G643R	0.998
10:123757232:A:G	L633P	0.998
10:123757235:G:A	S632F	0.998
10:123757241:C:G	R630P	0.998
10:123757265:A:G	L622P	0.998
10:123757292:C:A	C613F	0.998
10:123757293:A:G	C613R	0.998
10:123761888:C:A	W587C	0.998
10:123761888:C:G	W587C	0.998

dbSNP variants (sampled 300 via entrez): RS1000001076 (10:123815783 G>A), RS1000007137 (10:123939510 C>T), RS1000015908 (10:123936809 C>T), RS1000060024 (10:123857745 G>C), RS1000061880 (10:123802149 C>A,G), RS1000064760 (10:123818539 C>A,G,T), RS1000074759 (10:123818235 T>A), RS1000087573 (10:123857630 G>A), RS1000135305 (10:123895601 T>C), RS1000151869 (10:123849529 C>T), RS1000184229 (10:123846176 A>C), RS1000186121 (10:123763576 G>A,T), RS1000195277 (10:123852377 T>C), RS1000210169 (10:123797899 T>C), RS1000246884 (10:123821596 T>A,C)

Disease associations

OMIM: gene MIM:617348 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002548_6	Ulcerative colitis	7.000000e-06
GCST003518_93	Daytime sleep phenotypes	3.000000e-08
GCST008810_11	Smoking initiation (ever regular vs never regular)	8.000000e-09
GCST90000025_183	Appendicular lean mass	3.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0005670	smoking initiation
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
mercuric bromide	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
propionaldehyde	decreases expression	1
2,3-pentanedione	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases reaction, increases expression	1
Lead	affects methylation	1
Oxygen	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	increases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery