CNDP2

Summary

CNDP2 (carnosine dipeptidase 2, HGNC:24437) is a protein-coding gene on chromosome 18q22.3, encoding Cytosolic non-specific dipeptidase (Q96KP4). Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides.

CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).

Source: NCBI Gene 55748 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 110 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24437
Approved symbol	CNDP2
Name	carnosine dipeptidase 2
Location	18q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10830, CN2, HsT2298, CPGL
Ensembl gene	ENSG00000133313
Ensembl biotype	protein_coding
OMIM	169800
Entrez	55748

Gene structure

Transcript identifiers

Ensembl transcripts: 117 — 106 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324262, ENST00000324301, ENST00000577355, ENST00000577409, ENST00000577600, ENST00000577669, ENST00000579583, ENST00000579624, ENST00000579847, ENST00000580229, ENST00000580672, ENST00000581272, ENST00000581513, ENST00000581600, ENST00000581912, ENST00000582260, ENST00000582589, ENST00000582620, ENST00000582666, ENST00000583203, ENST00000583216, ENST00000583399, ENST00000583695, ENST00000583785, ENST00000583938, ENST00000584581, ENST00000584613, ENST00000584768, ENST00000585263, ENST00000880639, ENST00000880640, ENST00000880641, ENST00000880642, ENST00000880643, ENST00000880644, ENST00000880645, ENST00000880646, ENST00000880647, ENST00000880648, ENST00000880649, ENST00000880650, ENST00000880651, ENST00000880652, ENST00000880653, ENST00000880654, ENST00000880655, ENST00000880656, ENST00000880657, ENST00000880658, ENST00000880659, ENST00000880660, ENST00000880661, ENST00000880662, ENST00000880663, ENST00000880664, ENST00000880665, ENST00000880666, ENST00000880667, ENST00000880668, ENST00000880669, ENST00000880670, ENST00000880671, ENST00000880672, ENST00000880673, ENST00000880674, ENST00000880675, ENST00000880676, ENST00000880677, ENST00000880678, ENST00000880679, ENST00000880680, ENST00000880681, ENST00000880682, ENST00000880683, ENST00000880684, ENST00000880685, ENST00000880686, ENST00000880687, ENST00000880688, ENST00000880689, ENST00000880690, ENST00000880691, ENST00000880692, ENST00000921557, ENST00000921558, ENST00000921559, ENST00000921560, ENST00000921561, ENST00000921562, ENST00000921563, ENST00000921564, ENST00000921565, ENST00000921566, ENST00000921567, ENST00000921568, ENST00000921569, ENST00000921570, ENST00000921571, ENST00000921572, ENST00000921573, ENST00000921574, ENST00000921575, ENST00000921576, ENST00000921577, ENST00000969806, ENST00000969807, ENST00000969808, ENST00000969809, ENST00000969810, ENST00000969811, ENST00000969812, ENST00000969813, ENST00000969814, ENST00000969815, ENST00000969816, ENST00000969817, ENST00000969818

RefSeq mRNA: 6 — MANE Select: NM_018235 NM_001168499, NM_001370248, NM_001370249, NM_001370250, NM_001370254, NM_018235

CCDS: CCDS12006, CCDS54190

Canonical transcript exons

ENST00000324262 — 12 exons

Exon	Start	End
ENSE00001285531	74518949	74519096
ENSE00001285538	74518499	74518640
ENSE00001368884	74496363	74496431
ENSE00003459672	74516228	74516392
ENSE00003534022	74499882	74500033
ENSE00003536213	74510813	74511013
ENSE00003558286	74513559	74513719
ENSE00003571803	74512448	74512532
ENSE00003602340	74501329	74501472
ENSE00003668503	74508840	74508928
ENSE00003730043	74519999	74523454
ENSE00003784678	74505849	74506011

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.0571 / max 608.4942, expressed in 1822 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170750	42.9719	1822
170753	9.2047	910
170754	4.4312	674
170748	1.2705	493
170751	1.1935	419
170749	0.5749	280
170752	0.1617	93
170755	0.1426	79
170747	0.0815	37
170756	0.0202	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	99.22	gold quality
nephron tubule	UBERON:0001231	99.16	gold quality
renal medulla	UBERON:0000362	99.14	gold quality
endothelial cell	CL:0000115	99.11	gold quality
metanephros cortex	UBERON:0010533	99.02	gold quality
kidney epithelium	UBERON:0004819	98.95	gold quality
ileal mucosa	UBERON:0000331	98.90	gold quality
renal glomerulus	UBERON:0000074	98.74	gold quality
metanephric glomerulus	UBERON:0004736	98.58	gold quality
amniotic fluid	UBERON:0000173	98.56	gold quality
jejunal mucosa	UBERON:0000399	98.56	gold quality
cortex of kidney	UBERON:0001225	98.54	gold quality
kidney	UBERON:0002113	98.52	gold quality
corpus callosum	UBERON:0002336	98.50	gold quality
right uterine tube	UBERON:0001302	98.48	gold quality
pancreatic ductal cell	CL:0002079	98.45	gold quality
duodenum	UBERON:0002114	98.44	gold quality
gall bladder	UBERON:0002110	98.38	gold quality
cervix squamous epithelium	UBERON:0006922	98.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.33	gold quality
right lobe of liver	UBERON:0001114	98.32	gold quality
epithelium of nasopharynx	UBERON:0001951	98.29	gold quality
spinal cord	UBERON:0002240	98.23	gold quality
monocyte	CL:0000576	98.21	gold quality
palpebral conjunctiva	UBERON:0001812	98.18	gold quality
spleen	UBERON:0002106	98.16	gold quality
metanephros	UBERON:0000081	98.13	gold quality
mononuclear cell	CL:0000842	98.12	gold quality
leukocyte	CL:0000738	98.07	gold quality
right lobe of thyroid gland	UBERON:0001119	98.06	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	63.93
E-MTAB-10287	yes	46.75
E-CURD-112	yes	9.74
E-MTAB-6678	yes	8.10
E-MTAB-7606	no	442.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting CNDP2, 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-5193	100.00	67.26	1744
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6733-5P	99.74	67.94	2759

Literature-anchored findings (GeneRIF, showing 13)

• Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes (PMID:18753673)
• the crystal structure of the flop-selective allosteric modulator, PEPA, bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors (PMID:20199107)
• Common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes. (PMID:21573905)
• deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer. (PMID:22128300)
• a key role of CNDP2 in PD neurodegeneration, by mechanisms that could involve oxidative stress, protein aggregation or inflammation. (PMID:22410244)
• Results suggest that CNDP2 acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway. (PMID:24395568)
• Expression of CN2 in clinical colon tumors and colon cancer cell lines was significantly higher than that in normal colon mucosa cell lines. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo. (PMID:24885395)
• To identify substrates of orphan transporter ATP-binding cassette subfamily C member 5 (ABCC5), identified a class of metabolites, N-lactoyl-amino acids, and found that a protease, cytosolic nonspecific dipeptidase 2 (CNDP2), catalyzes their formation. (PMID:25964343)
• The CNDP2 rs6566810 (A/A genotype) is overrepresented in endurance athletes, but only in international-level endurance athletes. Three SNPs (CNDP2 rs3764509, CNDP2-CNDP1 rs2346061, and CNDP1 rs2887) were overrepresented in power athletes compared with nonathletes. (PMID:28871847)
• These results suggest that the zinc form of CN2 is an active enzyme, but with a different substrate specificity from that of the manganese form. (PMID:29056506)
• 2 SNPs (rs7244647 in CNDP1 and rs4891558 in CNDP2) were associated with obesity risk. In addition, these associations were observed only in the group with high carbohydrate and low carotene intake but not in the group with low carbohydrate and high carotene intake. (PMID:29402779)
• Cytosolic nonspecific dipeptidase 2 promotes the occurrence and development of ovarian cancer through the PI3K/AKT signaling pathway. (PMID:31537175)
• Exploring the structural and dynamic differences between human carnosinase I (CN1) and II (CN2). (PMID:36637795)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cndp2	ENSDARG00000003931
mus_musculus	Cndp2	ENSMUSG00000024644
rattus_norvegicus	Cndp2	ENSRNOG00000015591
drosophila_melanogaster	Cndp2	FBGN0287767

Paralogs (3): CNDP1 (ENSG00000150656), PM20D1 (ENSG00000162877), ACY1 (ENSG00000243989)

Protein

Protein identifiers

Cytosolic non-specific dipeptidase — Q96KP4 (reviewed: Q96KP4)

Alternative names: CNDP dipeptidase 2, Glutamate carboxypeptidase-like protein 1, Peptidase A, Threonyl dipeptidase

All UniProt accessions (17): A0A087WVS2, A0A087WYZ1, Q96KP4, J3KRD5, J3KRJ8, J3KSS4, J3KSV5, J3QKQ0, J3QKT2, J3QL02, J3QLU1, J3QQN6, J3QR27, J3QRA8, J3QRD0, J3QRH4, J3QRP4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides. Mediates threonyl dipeptide catabolism in a tissue-specific way. Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism. Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis. Plays a role in the regulation of cell cycle arrest and apoptosis.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed with higher levels in kidney and liver (at protein level). Expressed in peripheral blood leukocytes. Expressed in gastric mucosa and down-regulated in gastric cancer mucosal tissues (at protein level). Broadly expressed in fetal tissues. Expressed in adult liver and placenta.

Activity regulation. Inhibited by p-hydroxymercurybenzoate. The inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH 9.5.

Cofactor. Binds 2 manganese ions per subunit.

Miscellaneous. The reverse proteolysis is not negligible in vivo as long as the substrates are present in considerable concentrations, such as upon physical exercice. N-lac-Phe plasma levels are increased in patients with PKU with increased plasma Phe levels. N-lactoyl-amino acids are present in many tissues. Lacks a part of the catalytic domain.

Similarity. Belongs to the peptidase M20A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96KP4-1	1	yes
Q96KP4-2	2, CPGL-B

RefSeq proteins (6): NP_001161971, NP_001357177, NP_001357178, NP_001357179, NP_001357183, NP_060705* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001261	ArgE/DapE_CS	Conserved_site
IPR002933	Peptidase_M20	Family
IPR011650	Peptidase_M20_dimer	Domain
IPR017153	CNDP/DUG1	Family
IPR051458	Cyt/Met_Dipeptidase	Family

Pfam: PF01546, PF07687

Enzyme classification (BRENDA):

• EC 3.4.13.18 — cytosol nonspecific dipeptidase (BRENDA: 16 organisms, 105 substrates, 65 inhibitors, 99 Km, 42 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PRO-GLY	6.8–56.33	13
PRO-MET	4.2–46.78	13
PRO-VAL	3.2–75.2	13
ALA-PRO-P-NITROANILIDE	0.12–2.72	6
ALA-LEU	0.28–1	4
ARG-PRO-P-NITROANILIDE	0.027–1.673	4
GLY-PRO-P-NITROANILIDE	0.48–4.599	4
GLY-LEU	0.79–10	3
LEU-PRO-P-NITROANILIDE	0.023–0.39	3
LYS-PRO-P-NITROANILIDE	0.016–1.358	3
MET-PRO-P-NITROANILIDE	0.029–0.988	3
SER-PRO-P-NITROANILIDE	0.238–7.462	3
ASP-PRO-P-NITROANILIDE	2.05–2.668	2
GLY-ILE	4.4–10	2
GLY-L-LEU	3.16–10.6	2

Catalyzed reactions (Rhea), 6 shown:

• L-cysteinylglycine + H2O = L-cysteine + glycine (RHEA:28783)
• (S)-lactate + L-phenylalanine = N-[(S)-lactoyl]-L-phenylalanine + H2O (RHEA:66724)
• L-threonyl-L-threonine + H2O = 2 L-threonine (RHEA:67360)
• L-threonyl-L-serine + H2O = L-threonine + L-serine (RHEA:67364)
• L-seryl-L-threonine + H2O = L-threonine + L-serine (RHEA:67372)
• L-alanyl-L-cysteine + H2O = L-cysteine + L-alanine (RHEA:67380)

UniProt features (67 total): strand 21, helix 16, binding site 13, modified residue 4, turn 4, active site 2, sequence conflict 2, initiator methionine 1, chain 1, site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4RUH	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KP4-F1	97.84	0.98

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): 228 (important for catalytic activity); 101; 166 (proton acceptor)

Ligand- & substrate-binding residues (13): 195 (in other chain); 228; 330; 343 (in other chain); 417 (in other chain); 445; 445 (in other chain); 99; 132; 132; 166–167 (in other chain); 167 …

Post-translational modifications (4): 2, 9, 58, 299

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-174403	Glutathione synthesis and recycling
R-HSA-9753281	Paracetamol ADME

MSigDB gene sets: 185 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_METALLOPEPTIDASE_ACTIVITY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GARY_CD5_TARGETS_DN, BROWN_MYELOID_CELL_DEVELOPMENT_UP, REACTOME_GLUTATHIONE_CONJUGATION, chr18q22, DANG_BOUND_BY_MYC, CUI_TCF21_TARGETS_2_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_5, GOBP_PROTEOLYSIS

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

GO Molecular Function (8): carboxypeptidase activity (GO:0004180), dipeptidase activity (GO:0016805), metal ion binding (GO:0046872), metallodipeptidase activity (GO:0070573), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glutathione conjugation	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
exopeptidase activity	2
protein metabolic process	1
cation binding	1
metalloexopeptidase activity	1
dipeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNDP2	NARS1	O43776	846
CNDP2	PGC	P20142	793
CNDP2	CAGE1	Q8TC20	791
CNDP2	F13B	P05160	713
CNDP2	SCN8A	Q9UQD0	667
CNDP2	CARNS1	A5YM72	639
CNDP2	PEPD	P12955	618
CNDP2	DKKL1	Q9UK85	583
CNDP2	DPEP2	Q9H4A9	560
CNDP2	C4BPB	P20851	549
CNDP2	CFH	P08603	547
CNDP2	CFHR2	P36980	547
CNDP2	CFHR4	Q92496	547
CNDP2	CFHR5	Q9BXR6	544
CNDP2	CR1	P17927	542
CNDP2	SCN2A	Q99250	542

IntAct

32 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AGO2	FKBP5	psi-mi:“MI:0914”(association)	0.530
RAB8B	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CNDP1	POTEF	psi-mi:“MI:0914”(association)	0.530
NSUN2	LIN7A	psi-mi:“MI:0914”(association)	0.530
CNDP1	CNDP2	psi-mi:“MI:0915”(physical association)	0.500
CNDP2	CRK	psi-mi:“MI:0915”(physical association)	0.490
CRK	CNDP2	psi-mi:“MI:0915”(physical association)	0.490
NDRG1	CNDP2	psi-mi:“MI:0915”(physical association)	0.400
C8orf34	CNDP2	psi-mi:“MI:0915”(physical association)	0.400
CNDP2	STAT3	psi-mi:“MI:0915”(physical association)	0.370
STAT3	CNDP2	psi-mi:“MI:0915”(physical association)	0.370
DAPP1	CNDP2	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC17	CNDP2	psi-mi:“MI:0915”(physical association)	0.370
PB2		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
MAP2K4	PRKCZ	psi-mi:“MI:0914”(association)	0.350
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
LAGE3	HYKK	psi-mi:“MI:0914”(association)	0.350
LRRC36	TBL1X	psi-mi:“MI:0914”(association)	0.350
GAS2L2	ANKRD17	psi-mi:“MI:0914”(association)	0.350

BioGRID (161): CNDP2 (Affinity Capture-RNA), CNDP2 (Two-hybrid), CNDP2 (Affinity Capture-MS), CNDP2 (Co-fractionation), CNDP2 (Co-fractionation), CNDP2 (Co-fractionation), GDPGP1 (Co-fractionation), NMRAL1 (Co-fractionation), CNDP2 (Two-hybrid), CNDP2 (Two-hybrid), CNDP2 (Two-hybrid), CNDP2 (Affinity Capture-MS), CNDP2 (Affinity Capture-MS), CNDP2 (Affinity Capture-MS), CNDP2 (Affinity Capture-MS)

ESM2 similar proteins: A3KG59, A4IFH5, B9N1F9, D3ZVR9, O04059, O35331, O35621, O46560, P11172, P24298, P37111, Q03154, Q04609, Q15124, Q17QK3, Q2R483, Q501L1, Q5E9T8, Q5I0K3, Q5NAY4, Q5R514, Q5R5C9, Q5RDE7, Q5RDN7, Q5RFB0, Q5RFI8, Q6AY30, Q6AYS7, Q6K2E8, Q6PTT0, Q6Q0N1, Q6ZV70, Q7TSV4, Q7X7L3, Q8BZF8, Q8CG45, Q8CG76, Q8IYS1, Q8K183, Q8N0X4

Diamond homologs: A4WG54, A5F4Z7, A5IG28, A6Q4D7, A7FCZ8, A7MXC2, A7ZUH5, A8A765, A9MI13, A9N0G7, B0RW53, B0U296, B1IVC1, B1LNR7, B1XBC2, B2FIC0, B2I6B4, B2SQY5, B2TWF2, B2VGA3, B4F192, B4SQ35, B4T0W8, B4TCQ3, B4TQH3, B5BJN1, B5F0U6, B5FBP7, B5FPX2, B5QXQ2, B5RF48, B5XZ19, B5Z059, B6EMN5, B6I5H3, B7LA57, B7LUN8, B7M711, B7MI93, B7MR48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	81
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564570	GRCh37/hg19 18q21.31-23(chr18:55298900-78014123)x1	Pathogenic

SpliceAI

2473 predictions. Top by Δscore:

Variant	Effect	Δscore
18:74499935:A:G	acceptor_gain	1.0000
18:74506008:GACG:G	donor_gain	1.0000
18:74506062:A:T	donor_gain	1.0000
18:74510811:AG:A	acceptor_gain	1.0000
18:74510812:GG:G	acceptor_gain	1.0000
18:74510915:G:GT	donor_gain	1.0000
18:74511026:GCT:G	donor_gain	1.0000
18:74512528:GATGG:G	donor_gain	1.0000
18:74512531:GG:G	donor_gain	1.0000
18:74512532:GG:G	donor_gain	1.0000
18:74513554:CTCA:C	acceptor_loss	1.0000
18:74513556:CA:C	acceptor_loss	1.0000
18:74513557:A:AG	acceptor_gain	1.0000
18:74513557:AGG:A	acceptor_loss	1.0000
18:74513558:G:GA	acceptor_loss	1.0000
18:74513558:G:GG	acceptor_gain	1.0000
18:74513671:G:GT	donor_gain	1.0000
18:74513684:G:GT	donor_gain	1.0000
18:74516222:CTGCA:C	acceptor_loss	1.0000
18:74516224:GCA:G	acceptor_loss	1.0000
18:74516225:CA:C	acceptor_loss	1.0000
18:74516226:A:AG	acceptor_gain	1.0000
18:74516227:G:GA	acceptor_loss	1.0000
18:74516227:G:GG	acceptor_gain	1.0000
18:74516227:GAAA:G	acceptor_gain	1.0000
18:74518696:G:GT	donor_gain	1.0000
18:74518947:A:AG	acceptor_gain	1.0000
18:74518948:G:GA	acceptor_gain	1.0000
18:74518948:GTT:G	acceptor_gain	1.0000
18:74518948:GTTT:G	acceptor_gain	1.0000

AlphaMissense

3130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:74505975:T:A	W111R	1.000
18:74505975:T:C	W111R	1.000
18:74508866:G:C	D132H	1.000
18:74508867:A:T	D132V	1.000
18:74508868:T:A	D132E	1.000
18:74508868:T:G	D132E	1.000
18:74510853:A:T	E166V	1.000
18:74510939:G:C	D195H	1.000
18:74510940:A:T	D195V	1.000
18:74516352:G:T	R343M	1.000
18:74505939:C:G	H99D	0.999
18:74505941:C:A	H99Q	0.999
18:74505941:C:G	H99Q	0.999
18:74505945:G:C	D101H	0.999
18:74505946:A:T	D101V	0.999
18:74505953:G:C	Q103H	0.999
18:74505953:G:T	Q103H	0.999
18:74505977:G:C	W111C	0.999
18:74505977:G:T	W111C	0.999
18:74505990:T:C	F116L	0.999
18:74505992:C:A	F116L	0.999
18:74505992:C:G	F116L	0.999
18:74508852:G:A	G127E	0.999
18:74508855:G:C	R128T	0.999
18:74508857:G:C	G129R	0.999
18:74508866:G:T	D132Y	0.999
18:74508867:A:C	D132A	0.999
18:74508867:A:G	D132G	0.999
18:74508874:G:C	K134N	0.999
18:74508874:G:T	K134N	0.999

dbSNP variants (sampled 300 via entrez): RS1000097603 (18:74499348 G>A,C,T), RS1000101810 (18:74515541 C>T), RS1000174703 (18:74500748 A>G), RS1000273588 (18:74502990 A>G), RS1000291528 (18:74505178 C>T), RS1000388230 (18:74504902 A>G), RS1000421476 (18:74509946 G>A), RS1000568361 (18:74497552 A>G), RS1000817843 (18:74498759 T>C), RS1000881888 (18:74497021 G>A), RS1001038222 (18:74503670 C>G), RS1001104551 (18:74499086 A>G), RS1001161841 (18:74508647 T>C), RS1001372179 (18:74504541 T>C), RS1001437550 (18:74509942 G>C)

Disease associations

OMIM: gene MIM:169800 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001858_20	Refractive error	2.000000e-07
GCST010002_142	Refractive error	2.000000e-14
GCST012020_160	Serum metabolite levels	1.000000e-11
GCST012021_85	Serum metabolite levels	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066266 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M20: Carnosine dipeptidase

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.15	Kd	71.25	nM	CHEMBL5653589
7.15	ED50	71.25	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148096: Binding affinity to human CNDP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0712	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
Smoke	decreases expression, increases abundance, increases expression	3
bisphenol F	affects cotreatment, decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Metribolone	increases reaction, increases expression, affects binding	2
dicrotophos	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
quinoline	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	decreases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Dexamethasone	affects cotreatment, decreases 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
CHEMBL5651138	Binding	Binding affinity to human CNDP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1M3	Abcam K-562 CNDP2 KO	Cancer cell line	Female
CVCL_D2IN	Abcam Raji CNDP2 KO	Cancer cell line	Male
CVCL_UQ35	Abcam Jurkat CNDP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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