CPM

Summary

CPM (carboxypeptidase M, HGNC:2311) is a protein-coding gene on chromosome 12q15, encoding Carboxypeptidase M (P14384). Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins.

The protein encoded by this gene is a membrane-bound arginine/lysine carboxypeptidase. Its expression is associated with monocyte to macrophage differentiation. This encoded protein contains hydrophobic regions at the amino and carboxy termini and has 6 potential asparagine-linked glycosylation sites. The active site residues of carboxypeptidases A and B are conserved in this protein. Three alternatively spliced transcript variants encoding the same protein have been described for this gene.

Source: NCBI Gene 1368 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_198320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2311
Approved symbol	CPM
Name	carboxypeptidase M
Location	12q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135678
Ensembl biotype	protein_coding
OMIM	114860
Entrez	1368

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000338356, ENST00000546373, ENST00000546556, ENST00000546912, ENST00000547134, ENST00000547924, ENST00000548262, ENST00000548954, ENST00000549691, ENST00000549781, ENST00000551568, ENST00000551728, ENST00000551897, ENST00000894613, ENST00000894614, ENST00000894615, ENST00000894616, ENST00000894617, ENST00000894618, ENST00000961569, ENST00000961570, ENST00000961571, ENST00000961572, ENST00000961573, ENST00000961574, ENST00000961575

RefSeq mRNA: 21 — MANE Select: NM_198320 NM_001005502, NM_001413387, NM_001413388, NM_001413389, NM_001413390, NM_001413391, NM_001413392, NM_001413393, NM_001413394, NM_001413395, NM_001413396, NM_001413397, NM_001413398, NM_001413399, NM_001413400, NM_001413401, NM_001413402, NM_001413403, NM_001413404, NM_001874, NM_198320

CCDS: CCDS8987

Canonical transcript exons

ENST00000551568 — 9 exons

Exon	Start	End
ENSE00000920723	68858923	68859071
ENSE00000937239	68885792	68885889
ENSE00000937243	68866896	68867048
ENSE00002326579	68933142	68933171
ENSE00002372775	68851175	68856679
ENSE00003460608	68871784	68871956
ENSE00003469898	68870215	68870399
ENSE00003538101	68869325	68869495
ENSE00003542946	68932678	68932840

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5707 / max 553.8862, expressed in 993 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132000	8.4769	993
132003	0.0562	14
132002	0.0377	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	97.61	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.74	gold quality
adipose tissue	UBERON:0001013	94.27	gold quality
right lung	UBERON:0002167	94.22	gold quality
connective tissue	UBERON:0002384	93.43	gold quality
lung	UBERON:0002048	92.68	gold quality
visceral pleura	UBERON:0002401	92.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.24	gold quality
rectum	UBERON:0001052	92.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.94	gold quality
colonic mucosa	UBERON:0000317	91.70	gold quality
placenta	UBERON:0001987	91.68	gold quality
omental fat pad	UBERON:0010414	91.62	gold quality
peritoneum	UBERON:0002358	91.57	gold quality
upper lobe of lung	UBERON:0008948	91.44	gold quality
corpus callosum	UBERON:0002336	91.22	gold quality
colonic epithelium	UBERON:0000397	91.06	gold quality
upper lobe of left lung	UBERON:0008952	90.97	gold quality
nipple	UBERON:0002030	90.23	gold quality
gall bladder	UBERON:0002110	90.10	gold quality
renal medulla	UBERON:0000362	90.05	gold quality
skin of leg	UBERON:0001511	89.25	gold quality
adult mammalian kidney	UBERON:0000082	88.79	gold quality
layer of synovial tissue	UBERON:0007616	88.17	gold quality
upper arm skin	UBERON:0004263	88.11	gold quality
synovial joint	UBERON:0002217	87.97	gold quality
islet of Langerhans	UBERON:0000006	87.84	gold quality
zone of skin	UBERON:0000014	87.83	gold quality
endometrium	UBERON:0001295	87.77	gold quality
buccal mucosa cell	CL:0002336	87.60	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	878.43
E-MTAB-8221	yes	746.52
E-MTAB-10662	yes	658.52
E-MTAB-10283	yes	355.55
E-HCAD-1	yes	32.17
E-CURD-119	yes	15.83
E-CURD-46	yes	14.60
E-GEOD-130148	yes	11.45
E-GEOD-134144	yes	11.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting CPM, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977

Literature-anchored findings (GeneRIF, showing 14)

• Multiple transcription start sites in two regions ~30 kb apart are flanked by two unique functional promoters. Five major types of transcripts resulting from multiple transcription start sites and alternate splicing in the 5-prime region were identified. (PMID:11891060)
• CPM is membrane-bound via attachment of glycosylphosphatidylinositol at Ser406. Glu264 is a critical catalytic residue, whereas Glu260 affects stability and substrate kinetics. (PMID:12457462)
• Results report the crystallization of human carboxypeptidase M and its 3.0 angstrom crystal structure. (PMID:15066430)
• Carboxypeptidase M and kinin B1 receptors interact to facilitate efficient b1 signaling from B2 agonists (PMID:18187413)
• Cleavage of the C-terminal lysine residue of SDF-1alpha by CPM leads to attenuated chemotactic responses. (PMID:18292211)
• CPM amplification could be used as an alternative diagnostic tool for the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumors. (PMID:19820690)
• CPM and B1Rs on cell membranes form a critical complex that potentiates B1R signaling. (PMID:21454694)
• novel marker and cellular player in lipid uptake and/or metabolism of activated macrophages by promoting foam cell formation (PMID:22157720)
• Carboxypeptidase M expression is lost in human renal cell carcinoma tumor cells, whereas it is abundant in tumor-associated foam cells and neovasculature. (PMID:23172796)
• CPM binding to extracellular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption of this interaction could provide a novel therapeutic approach to reduce pathological B1R signaling. (PMID:24108126)
• Low CPM expression is associated with colorectal cancer. (PMID:28186967)
• The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility. (PMID:30674606)
• Our work shows for the first time that the interaction between CPM and kinin B1 receptor alters not only B1R pharmacology, but also modulates enzyme expression and activity. (PMID:31218444)
• Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study. (PMID:38713087)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpm	ENSDARG00000011769
mus_musculus	Cpm	ENSMUSG00000020183
rattus_norvegicus	Cpm	ENSRNOG00000084862
drosophila_melanogaster	CG4678	FBGN0030778

Paralogs (7): CPXM1 (ENSG00000088882), AEBP1 (ENSG00000106624), CPD (ENSG00000108582), CPE (ENSG00000109472), CPZ (ENSG00000109625), CPN1 (ENSG00000120054), CPXM2 (ENSG00000121898)

Protein

Protein identifiers

Carboxypeptidase M — P14384 (reviewed: P14384)

All UniProt accessions (7): P14384, F8VR29, F8VU13, F8VVI6, F8W111, H0YHG6, H0YHN7

UniProt curated annotations — full annotation on UniProt →

Function. Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins.

Subcellular location. Cell membrane.

Activity regulation. Inhibited by O-phenanthroline and MGTA and activated by cobalt.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

RefSeq proteins (21): NP_001005502, NP_001400316, NP_001400317, NP_001400318, NP_001400319, NP_001400320, NP_001400321, NP_001400322, NP_001400323, NP_001400324, NP_001400325, NP_001400326, NP_001400327, NP_001400328, NP_001400329, NP_001400330, NP_001400331, NP_001400332, NP_001400333, NP_001865, NP_938079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR033842	CPM_N	Domain
IPR050753	Peptidase_M14_domain	Family
IPR057246	CARBOXYPEPT_ZN_1	Binding_site
IPR057247	CARBOXYPEPT_ZN_2	Binding_site

Pfam: PF00246, PF13620

Enzyme classification (BRENDA):

• EC 3.4.17.12 — carboxypeptidase M (BRENDA: 7 organisms, 61 substrates, 26 inhibitors, 48 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DANSYL-ALA-ARG	0.059–0.28	5
BENZOYL-ALA-ARG	0.115–0.18	3
BENZOYL-GLY-ARG	0.255–0.29	3
BENZOYL-MET-ARG	0.13–0.138	3
BENZOYL-GLY-ARGININIC ACID	0.046–0.049	2
BENZOYL-GLY-LYS	10.15–10.65	2
BRADYKININ	0.016	2
FURYLACRYLOYL-ALA-ARG	0.068–0.09	2
N-(4-HYDROXYBENZOYL)-GLY-ARG	0.206–0.241	2
ALA-SER-HIS-LEU-GLY-LEU-ALA-ARG	0.033	1
BENZOYL-ASN-ARG	0.343	1
BENZOYL-GLN-ARG	0.127	1
BENZOYL-HIS-ARG	0.239	1
BENZOYL-ILE-ARG	0.205	1
BENZOYL-LEU-ARG	0.168	1

UniProt features (61 total): strand 18, helix 13, glycosylation site 5, mutagenesis site 5, turn 5, disulfide bond 3, binding site 3, sequence variant 2, signal peptide 1, chain 1, propeptide 1, domain 1, active site 1, site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1UWY	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14384-F1	90.49	0.82

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 (2): 281 (proton donor/acceptor); 277 (probable structural role)

Ligand- & substrate-binding residues (3): 83; 86; 190

Post-translational modifications (1): 423

Disulfide bonds (3): 138–285, 242–284, 341–410

Glycosylation sites (5): 38, 115, 164, 363, 384

Mutagenesis-validated functional residues (5):

Position	Phenotype
277	5-fold decrease in substrate affinity. 22-fold decrease in specific affinity. 104-fold decrease in catalytic efficiency.
277	2-fold decrease in substrate affinity. small increase in specific affinity. reduced heat stability by 50%.
281	abolishes enzyme activity.
423	expressed on cell membrane. released from membrane by pi-plc.
423	little expression on cell membrane. perinuclear localization. not released from membrane by pi-plc.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 257 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, MODULE_172, ACTACCT_MIR196A_MIR196B, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_522, GOCC_CELL_SURFACE, MODULE_128, KANNAN_TP53_TARGETS_DN, GOBP_PEPTIDE_METABOLIC_PROCESS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_PROTEIN_MATURATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN

GO Biological Process (4): peptide metabolic process (GO:0006518), anatomical structure morphogenesis (GO:0009653), protein processing (GO:0016485), proteolysis (GO:0006508)

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

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
metabolic process	1
developmental process	1
anatomical structure development	1
proteolysis	1
protein maturation	1
protein metabolic process	1
exopeptidase activity	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cell periphery	1
extracellular vesicle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPM	BDKRB1	P46663	786
CPM	KNG1	P01042	582
CPM	GOLPH3	Q9H4A6	571
CPM	BDKRB2	P30411	559
CPM	YEATS4	O95619	488
CPM	PREP	P48147	480
CPM	KLK4	Q9Y5K2	475
CPM	C12orf71	A8MTZ7	472
CPM	ACE	P12821	446
CPM	MME	P08473	431
CPM	FRS2	Q8WU20	421
CPM	PRCP	P42785	417
CPM	DPP4	P27487	416
CPM	SFTPC	P11686	410
CPM	KLKB1	P03952	409

IntAct

58 interactions, top by confidence:

A	B	Type	Score
Zfp36	CNOT1	psi-mi:“MI:0914”(association)	0.560
ZSCAN12	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
ULBP1	IGLL5	psi-mi:“MI:0914”(association)	0.530
CPM	GTPBP3	psi-mi:“MI:0915”(physical association)	0.400
Trim69		psi-mi:“MI:0915”(physical association)	0.400
	RAP1BL	psi-mi:“MI:0915”(physical association)	0.400
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ATP6AP2	TMUB1	psi-mi:“MI:0914”(association)	0.350
FLNA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myh10	LMO7	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
RAB7A		psi-mi:“MI:0914”(association)	0.350
Chmp4b		psi-mi:“MI:0914”(association)	0.350
Flnb	RPL22	psi-mi:“MI:0914”(association)	0.350
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tmod3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tpm1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DBN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS), CPM (Affinity Capture-MS)

ESM2 similar proteins: A5A6K7, O17754, O54858, O75976, O89001, P04836, P14384, P15087, P15169, P16870, P21661, P23188, P23377, P28841, P29122, P37892, P38836, P42787, Q00493, Q0II73, Q16769, Q28193, Q2KIG3, Q2KJ83, Q4R4M3, Q4R7R2, Q5REC2, Q5RFD6, Q5U901, Q63415, Q66K79, Q80V42, Q8IVL8, Q8N436, Q8QGP3, Q8R4H4, Q8R4V4, Q8WXQ8, Q90240, Q96IY4

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

1 interactions.

A	Effect	B	Mechanism
CPM	“down-regulates activity”	HBA1	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2386 predictions. Top by Δscore:

Variant	Effect	Δscore
12:68856680:C:A	acceptor_loss	1.0000
12:68856680:C:CC	acceptor_gain	1.0000
12:68856681:T:G	acceptor_loss	1.0000
12:68858919:TTA:T	donor_loss	1.0000
12:68858920:TA:T	donor_loss	1.0000
12:68858921:A:AC	donor_gain	1.0000
12:68858922:C:CC	donor_gain	1.0000
12:68858922:CA:C	donor_gain	1.0000
12:68858922:CAT:C	donor_gain	1.0000
12:68858922:CATT:C	donor_gain	1.0000
12:68858922:CATTT:C	donor_gain	1.0000
12:68858965:T:A	donor_gain	1.0000
12:68859067:TACAC:T	acceptor_gain	1.0000
12:68859068:ACAC:A	acceptor_gain	1.0000
12:68859069:CAC:C	acceptor_gain	1.0000
12:68859069:CACC:C	acceptor_gain	1.0000
12:68859070:AC:A	acceptor_gain	1.0000
12:68859071:CC:C	acceptor_gain	1.0000
12:68859072:C:CA	acceptor_loss	1.0000
12:68859072:C:CC	acceptor_gain	1.0000
12:68859073:T:C	acceptor_loss	1.0000
12:68869322:CA:C	donor_loss	1.0000
12:68869323:A:AC	donor_gain	1.0000
12:68869324:C:CC	donor_gain	1.0000
12:68869324:C:CT	donor_loss	1.0000
12:68869425:A:C	acceptor_gain	1.0000
12:68869431:A:C	acceptor_gain	1.0000
12:68869433:G:GC	acceptor_gain	1.0000
12:68869443:T:TC	acceptor_gain	1.0000
12:68869528:CTGA:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002086 (12:68873156 C>A), RS1000053632 (12:68917795 A>G,T), RS1000055740 (12:68855769 T>G), RS1000065196 (12:68844417 T>G), RS1000091227 (12:68845383 T>C,G), RS1000092329 (12:68863716 GC>G), RS1000094061 (12:68907278 G>C), RS1000134105 (12:68926092 ATTT>A), RS1000164465 (12:68883166 T>C), RS1000166957 (12:68875604 G>A,C), RS1000255081 (12:68867143 T>A,G), RS1000263880 (12:68872876 A>G), RS1000276127 (12:68906899 C>T), RS1000277108 (12:68925730 T>C), RS1000323785 (12:68952670 G>A)

Disease associations

OMIM: gene MIM:114860 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000743_1	Major depressive disorder	3.000000e-06
GCST002515_1	Pneumoconiosis in silica exposure	2.000000e-08
GCST006138_31	Resting-state electroencephalogram vigilance	6.000000e-06
GCST007160_22	Refractive astigmatism	8.000000e-06
GCST008526_66	Coffee consumption	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0006781	coffee consumption measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3038 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M14: Carboxypeptidase A

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 14640538]	Inhibition	7.89	pIC50

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.89	IC50	13	nM	CHEMBL150332

PubChem BioAssay actives

1 with measured affinity, of 11 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4,4-diaminobut-3-enylsulfanylmethyl)-3-sulfanylpropanoic acid	48647: In vitro inhibition of purified Carboxypeptidase M (CPM) by clot lysis assay in human plasma	ic50	0.0130	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Progesterone	affects cotreatment, decreases expression, increases expression	4
Valproic Acid	affects expression, increases expression	4
trichostatin A	increases expression	2
sodium arsenite	affects splicing, decreases expression	2
(+)-JQ1 compound	increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
4-hydroxyphenyl 4-isopropoxyphenylsulfone	increases expression	1
afimoxifene	increases expression	1
sulforaphane	decreases expression	1
manganese chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
gardiquimod	increases expression, decreases reaction	1
Resveratrol	increases expression, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL660086	Binding	In vitro inhibition of purified Carboxypeptidase M (CPM) by clot lysis assay in human plasma	Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms