CNDP1

Summary

CNDP1 (carnosine dipeptidase 1, HGNC:20675) is a protein-coding gene on chromosome 18q22.3, encoding Beta-Ala-His dipeptidase (Q96KN2). Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides, displaying the highest activity toward carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-3-methyl-histidine).

This gene encodes a member of the M20 metalloprotease family. The encoded protein is specifically expressed in the brain, is a homodimeric dipeptidase which was identified as human carnosinase. This gene contains trinucleotide (CTG) repeat length polymorphism in the coding region.

Source: NCBI Gene 84735 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 107 total — 1 pathogenic
• MANE Select transcript: NM_032649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20675
Approved symbol	CNDP1
Name	carnosine dipeptidase 1
Location	18q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10825, CN1, CPGL2, HsT2308
Ensembl gene	ENSG00000150656
Ensembl biotype	protein_coding
OMIM	609064
Entrez	84735

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000358821, ENST00000578498, ENST00000582365, ENST00000582461, ENST00000584004, ENST00000584316, ENST00000585136, ENST00000864762, ENST00000864763, ENST00000864764, ENST00000864765, ENST00000954332

RefSeq mRNA: 1 — MANE Select: NM_032649 NM_032649

CCDS: CCDS12007

Canonical transcript exons

ENST00000358821 — 12 exons

Exon	Start	End
ENSE00000995771	74560856	74561018
ENSE00001881512	74534500	74534691
ENSE00002725039	74584496	74587212
ENSE00003475158	74578163	74578327
ENSE00003487941	74556338	74556466
ENSE00003570602	74562047	74562135
ENSE00003579708	74580130	74580271
ENSE00003584102	74559323	74559472
ENSE00003594412	74576869	74577029
ENSE00003600761	74571186	74571270
ENSE00003616584	74583561	74583708
ENSE00003632043	74567233	74567433

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 99.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.0331 / max 555.5756, expressed in 92 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170763	1.9688	78
170759	1.9092	83
170760	1.0806	78
170762	0.4716	76
170761	0.3099	74
170758	0.1622	62
170767	0.1307	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.23	gold quality
endothelial cell	CL:0000115	98.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.84	gold quality
spinal cord	UBERON:0002240	98.70	gold quality
medulla oblongata	UBERON:0001896	98.29	gold quality
corpus callosum	UBERON:0002336	98.28	gold quality
pons	UBERON:0000988	98.27	gold quality
superior vestibular nucleus	UBERON:0007227	98.11	gold quality
ventral tegmental area	UBERON:0002691	98.10	gold quality
subthalamic nucleus	UBERON:0001906	97.84	gold quality
midbrain	UBERON:0001891	97.35	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.25	gold quality
substantia nigra	UBERON:0002038	97.24	gold quality
globus pallidus	UBERON:0001875	96.72	gold quality
lateral globus pallidus	UBERON:0002476	96.56	gold quality
medial globus pallidus	UBERON:0002477	96.55	gold quality
putamen	UBERON:0001874	96.34	gold quality
pigmented layer of retina	UBERON:0001782	96.20	gold quality
Ammon’s horn	UBERON:0001954	95.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.02	gold quality
occipital lobe	UBERON:0002021	94.24	gold quality
primary visual cortex	UBERON:0002436	93.99	gold quality
caudate nucleus	UBERON:0001873	93.97	gold quality
substantia nigra pars compacta	UBERON:0001965	93.86	gold quality
amygdala	UBERON:0001876	93.79	gold quality
hypothalamus	UBERON:0001898	93.50	gold quality
postcentral gyrus	UBERON:0002581	93.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.26	gold quality
parietal lobe	UBERON:0001872	93.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.96	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1722.49
E-GEOD-84465	yes	13.01
E-ANND-3	yes	5.86
E-MTAB-8060	no	49.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting CNDP1, 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-432-3P	100.00	67.86	705
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-6737-3P	98.95	68.56	1577

Literature-anchored findings (GeneRIF, showing 37)

• GCP II mRNA was detected in glial cells. Glial-rich regions, specifically the DLPFC and ERC white matter and the molecular and polymorphic layers in the hippocampus, express high levels of GCP II mRNA. (PMID:14560319)
• diabetic patients with the carnosinase CNDP1 gene Mannheim variant are less susceptible for nephropathy (PMID:16046297)
• no difference in allele or genotype frequency between centenarians & controls or between cardiovascular patients & controls; the recently identified functional carnosinase variant does not contribute to longevity or protect against coronary heart disease (PMID:16965804)
• CPGL-B may be associated with cell growth and metastasis of HCC. (PMID:17121880)
• This replicates the CNDP1 gene association with diabetic nephropathy (DN) that was initially detected in European Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and carnosine pathway appear to play a role in susceptibility to DN. (PMID:17205963)
• Diabetic patients homozygous for CNDP1 are protected against diabetic nephropathy. (PMID:17601991)
• CN1-dependent susceptibility to diabetic nephropathy may at least in part be mediated by altered glucose metabolism in type 2 diabetic patients. (PMID:17601992)
• 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)
• South Asian Surinamese have a lower frequency of the 5/5 homozygous genotype, which was associated with lower carnosinase activity and genetic risk for developing diabetic nephropathy. (PMID:19577318)
• Association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes. (PMID:20332346)
• Hyperglycemia enhances CNDP1 secretion and enzyme activity; data suggest that poor blood glucose control in diabetic patients might result in an increased enzyme secretion even in the presence of the (CTG)(5) allele. (PMID:20460427)
• CNDP1 polymorphism predicts progression to ESRD in patients with diabetic nephropathies, but only late after baseline measurements. (PMID:20711718)
• neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content (PMID:20865290)
• Serum histidine dipeptide concentrations are not correlated to serum carnosinase activity (PMID:20971102)
• CTG polymorphism of the CNDP1 gene does not affect survival of Chinese peritoneal dialysis subjects. (PMID:20979941)
• These findings provide nominal evidence supporting a role between CNDP1 variants and diabetic kidney disease. (PMID:21393041)
• Common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes. (PMID:21573905)
• In this review, correlations between serum carnosine and carnosinase activity and polymorphism in CNDP1 gene are analyzed. The role of CNDP1 gene polymorphism the development of diabetic nephropathy and non-diabetic chronic kidney disease is discussed. (PMID:22706107)
• Plasma levels of FLT and S100A9 proteins are up-regulated and CNDP1 levels are down-regulated in patients with glioblastoma. (PMID:23029420)
• Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes. (PMID:23342076)
• This meta-analysis confirms that the carnosinase D18S880 microsatellite polymorphism is associated with daibetic nephropathy susceptibility, especially in the type 2 DM and the Caucasian population. (PMID:23402577)
• Alterations of serum carnosinase (CN1) activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer (PMID:24566305)
• In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. (PMID:25898255)
• CNDP1 and CARNS are expressed in glomeruli and tubular cells; TauT is expressed in renal epithelial cells; CDNP1 may have a role in diabetic neuropathy (PMID:26206726)
• Data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. (PMID:26439389)
• The experimentally measured higher affinity of homocarnosine for the enzyme relative to l-carnosine might be explained, at least in part, by more extensive interactions inside the monomeric and dimeric hCN1’s active site. (PMID:27105448)
• genetic association studies in pediatric population in Germany: Data suggest that, in pediatric patients with chronic kidney disease, the nephroprotective effect of CNDP1 Mannheim genetic variant against disease progression is not restricted to patients with diabetic nephropathy. (PMID:27278783)
• Considering that approximately 40 per cent of the population are homozygous for the 5L allele of (CTG) n repeat polymorphism in CNDP1 gene and seem to be less prone to develop DN, it is needed to evaluate whether the majority of diabetic patients (who do not have the 5L-5L genotype) would be benefited from supplementation with carnosine or with a more intensive monitoring (PMID:27834319)
• Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population. (PMID:27834323)
• The distribution of the (CTG)5 homozygous genotype in the no-diabetic nephropathy (DN) and clinical-DN patients was comparable, a lower frequency was found in the biopsy proven-DN patients, particularly in females. We observed a significant trend towards high frequencies of the (CTG)5 homozygous genotype with increased time on dialysis. (PMID:28553654)
• 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)
• 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)
• Lower serum CNDP1 concentrations correlated with impaired renal function and to a lesser extend with the CNDP1 genotype in patients with type 2 diabetes. (PMID:30610469)
• Genotype Distribution of CNDP1 Polymorphisms in the Healthy Chinese Han Population: Association with HbA1c and Fasting Blood Glucose. (PMID:32733966)
• Human carnosinase 1 overexpression aggravates diabetes and renal impairment in BTBR(Ob/Ob) mice. (PMID:32803273)
• Correlation between serum carnosinase concentration and renal damage in diabetic nephropathy patients. (PMID:33811534)
• Exploring the structural and dynamic differences between human carnosinase I (CN1) and II (CN2). (PMID:36637795)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cndp1	ENSMUSG00000056162
rattus_norvegicus	Cndp1	ENSRNOG00000027739

Paralogs (3): CNDP2 (ENSG00000133313), PM20D1 (ENSG00000162877), ACY1 (ENSG00000243989)

Protein

Protein identifiers

Beta-Ala-His dipeptidase — Q96KN2 (reviewed: Q96KN2)

Alternative names: CNDP dipeptidase 1, Carnosine dipeptidase 1, Glutamate carboxypeptidase-like protein 2, Serum carnosinase

All UniProt accessions (3): Q96KN2, J3KRP0, J3QQM7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides, displaying the highest activity toward carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-3-methyl-histidine).

Subunit / interactions. Homodimer.

Subcellular location. Secreted.

Tissue specificity. Found in serum and adult nervous central system. Absent in serum from patients with homocarnosinosis.

Activity regulation. Activated by cadmium ions. Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC(50)) is 5 uM.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Polymorphism. The number of trinucleotide (CTG) repeat varies among different alleles leading to insertion of Leu residues in the signal peptide. The allele with 5 leucines (as shown in the reference entry) is known as the Mannheim allele. Diabetic patients with the CNDP1 Mannheim allele are less susceptible for nephropathy.

Similarity. Belongs to the peptidase M20A family.

RefSeq proteins (1): NP_116038* (*=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 3.4.13.20 — beta-Ala-His dipeptidase (BRENDA: 6 organisms, 75 substrates, 22 inhibitors, 26 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CARNOSINE	0.175–1.1	9
D-ALA-4-NITROANILIDE	0.52–2.3	3
BETA-ALA-L-HIS	1.27–11	2
HOMOCARNOSINE	0.2–1.9	2
L-ALA-4-NITROANILIDE	0.36–0.6	2
ANSERINE	1.96	1
BETA-ALA-4-NITROANILIDE	0.0039	1
BETA-HOMOALA-4-NITROANILIDE	0.019	1
BETA-HOMOPHE-4-NITROANILIDE	1.1	1
GLY-4-NITROANILIDE	3	1
L-ARG-4-NITROANILIDE	0.4	1
L-LYS-4-NITROANILIDE	0.4	1

Catalyzed reactions (Rhea), 5 shown:

• L-alanyl-L-histidine + H2O = L-histidine + L-alanine (RHEA:37283)
• carnosine + H2O = beta-alanine + L-histidine (RHEA:59360)
• L-homocarnosine + H2O = 4-aminobutanoate + L-histidine (RHEA:59572)
• anserine + H2O = N(pros)-methyl-L-histidine + beta-alanine (RHEA:59576)
• glycyl-L-histidine + H2O = L-histidine + glycine (RHEA:67376)

UniProt features (60 total): strand 18, helix 15, binding site 6, turn 5, sequence variant 3, mutagenesis site 3, sequence conflict 3, glycosylation site 2, active site 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3DLJ	X-RAY DIFFRACTION	2.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KN2-F1	94.16	0.91

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): 134; 199 (proton acceptor)

Ligand- & substrate-binding residues (6): 132; 165; 165; 200; 228; 478

Post-translational modifications (1): 219

Glycosylation sites (2): 322, 382

Mutagenesis-validated functional residues (3):

Position	Phenotype
132	loss of activity.
165	loss of activity.
200	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, KEGG_HISTIDINE_METABOLISM, chr18q22, MODULE_95, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_DIPEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY, MODULE_49, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, MODULE_163, KEGG_BETA_ALANINE_METABOLISM, CBX5_TARGET_GENES

GO Biological Process (2): proteolysis (GO:0006508), regulation of protein metabolic process (GO:0051246)

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 (2): extracellular region (GO:0005576), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
exopeptidase activity	2
cellular anatomical structure	2
regulation of macromolecule metabolic process	1
regulation of primary 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
cytoplasm	1

Protein interactions and networks

STRING

1988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNDP1	CARNS1	A5YM72	779
CNDP1	PEPD	P12955	582
CNDP1	ELMO1	Q92556	544
CNDP1	FRMD3	A2A2Y4	542
CNDP1	PGC	P20142	509
CNDP1	CPVL	Q9H3G5	502
CNDP1	A0A2R8YEI5	A0A2R8YEI5	472
CNDP1	SLC15A2	Q16348	458
CNDP1	TMEM252	Q8N6L7	451
CNDP1	CARNMT1	Q8N4J0	442
CNDP1	SLC15A1	P46059	440
CNDP1	CCL5	P13501	433
CNDP1	CHN2	P52757	430
CNDP1	SLC15A4	Q8N697	424
CNDP1	PM20D2	Q8IYS1	412

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CNDP1	POTEF	psi-mi:“MI:0914”(association)	0.530
ESR1	PGK2	psi-mi:“MI:0914”(association)	0.530
CNDP1	CNDP2	psi-mi:“MI:0915”(physical association)	0.500
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): HSP90AB4P (Affinity Capture-MS), POTEF (Affinity Capture-MS), RAB3B (Affinity Capture-MS), CNDP2 (Affinity Capture-MS), SLC25A16 (Affinity Capture-MS), COX7A2 (Affinity Capture-MS), PIGM (Affinity Capture-MS), ARF5 (Affinity Capture-MS), WRB (Affinity Capture-MS), MANEA (Affinity Capture-MS), SCD5 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), CNDP2 (Affinity Capture-MS), SLC16A10 (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: A0RNM0, A1ADX7, A5FYQ7, A5UB44, A5UFQ7, A5VCF0, A6Q4D7, A6Q7J0, A7GX37, A7I005, A7ZFC1, A7ZPR5, A8A2W3, A8ETY6, A8FMA1, A9HKR2, A9ILD7, B0RW53, B0U296, B1IWI8, B1LNC1, B1XAE3, B2FIC0, B2I6B4, B2SQY5, B2TXP7, B3CLN1, B4SQ35, B5Z008, B5Z9Y1, B6I539, B6IPH8, B6JKE4, B7LCK7, B7LKH0, B7M7H2, B7MHW4, B7N653, B7NQK9, B7UGM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	78
Likely benign	16
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526627	GRCh37/hg19 18q21.2-23(chr18:53309113-78014123)	Pathogenic

SpliceAI

1924 predictions. Top by Δscore:

Variant	Effect	Δscore
18:74556465:AGG:A	donor_loss	1.0000
18:74556466:GGTAG:G	donor_loss	1.0000
18:74556467:G:A	donor_loss	1.0000
18:74556468:T:G	donor_loss	1.0000
18:74559318:CCTA:C	acceptor_loss	1.0000
18:74559320:TAGAC:T	acceptor_loss	1.0000
18:74559321:A:AC	acceptor_loss	1.0000
18:74559321:A:AG	acceptor_gain	1.0000
18:74559321:AGAC:A	acceptor_gain	1.0000
18:74559322:G:A	acceptor_loss	1.0000
18:74559322:G:GA	acceptor_gain	1.0000
18:74559322:GA:G	acceptor_gain	1.0000
18:74559322:GAC:G	acceptor_gain	1.0000
18:74559322:GACG:G	acceptor_gain	1.0000
18:74559322:GACGC:G	acceptor_gain	1.0000
18:74559473:GTGCT:G	donor_gain	1.0000
18:74561009:G:GT	donor_gain	1.0000
18:74562043:AAAG:A	acceptor_gain	1.0000
18:74562132:GCAA:G	donor_gain	1.0000
18:74562136:G:GG	donor_gain	1.0000
18:74567382:G:GT	donor_gain	1.0000
18:74567431:G:GT	donor_gain	1.0000
18:74583553:T:TA	acceptor_gain	1.0000
18:74583559:A:AG	acceptor_gain	1.0000
18:74583559:AGT:A	acceptor_gain	1.0000
18:74583560:G:GA	acceptor_gain	1.0000
18:74583560:GT:G	acceptor_gain	1.0000
18:74583560:GTG:G	acceptor_gain	1.0000
18:74583560:GTGT:G	acceptor_gain	1.0000
18:74583560:GTGTT:G	acceptor_gain	1.0000

AlphaMissense

3325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:74562080:A:T	K167I	0.992
18:74562081:A:C	K167N	0.992
18:74562081:A:T	K167N	0.992
18:74559350:A:C	S61R	0.989
18:74559352:C:A	S61R	0.989
18:74559352:C:G	S61R	0.989
18:74560934:T:C	C128R	0.989
18:74578278:T:C	F373S	0.988
18:74583696:A:T	E482V	0.988
18:74571256:T:C	L276P	0.987
18:74560952:G:C	D134H	0.986
18:74578287:G:C	R376P	0.986
18:74560936:C:G	C128W	0.985
18:74562059:G:A	G160E	0.985
18:74578280:T:C	S374P	0.985
18:74583697:G:C	E482D	0.985
18:74583697:G:T	E482D	0.985
18:74560982:T:A	W144R	0.984
18:74560982:T:C	W144R	0.984
18:74559335:T:A	W56R	0.983
18:74559335:T:C	W56R	0.983
18:74562074:A:T	D165V	0.983
18:74562097:T:A	W173R	0.983
18:74562097:T:C	W173R	0.983
18:74580259:G:C	A433P	0.983
18:74562106:G:C	A176P	0.982
18:74584520:A:C	K494N	0.982
18:74584520:A:T	K494N	0.982
18:74562073:G:C	D165H	0.981
18:74584512:G:A	G492R	0.981

dbSNP variants (sampled 300 via entrez): RS1000045621 (18:74572824 G>A,T), RS1000082871 (18:74585500 C>T), RS1000110430 (18:74534369 G>A,C), RS1000178913 (18:74534186 C>T), RS1000249759 (18:74571860 T>C,G), RS1000303805 (18:74578554 G>T), RS1000335909 (18:74534755 G>A,T), RS1000347877 (18:74572853 A>G), RS1000355875 (18:74546591 T>A), RS1000450489 (18:74535014 G>A), RS1000458667 (18:74583987 C>G,T), RS1000466813 (18:74546406 A>G), RS1000495702 (18:74566499 C>T), RS1000522024 (18:74576911 T>C,G), RS1000539270 (18:74570216 A>G,T)

Disease associations

OMIM: gene MIM:609064 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004797_5	Brain volume in infants (grey matter)	4.000000e-07
GCST006585_506	Blood protein levels	1.000000e-28
GCST006585_925	Blood protein levels	9.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008368	infant grey matter volume measurement

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 — M20: Carnosine dipeptidase

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects methylation, decreases expression	2
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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