CARNS1

Summary

CARNS1 (carnosine synthase 1, HGNC:29268) is a protein-coding gene on chromosome 11q13.2, encoding Carnosine synthase 1 (A5YM72). Catalyzes the synthesis of carnosine and homocarnosine.

CARNS1 (EC 6.3.2.11), a member of the ATP-grasp family of ATPases, catalyzes the formation of carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine), which are found mainly in skeletal muscle and the central nervous system, respectively (Drozak et al., 2010 [PubMed 20097752]).

Source: NCBI Gene 57571 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 191 total
• MANE Select transcript: NM_001166222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29268
Approved symbol	CARNS1
Name	carnosine synthase 1
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1394
Ensembl gene	ENSG00000172508
Ensembl biotype	protein_coding
OMIM	613368
Entrez	57571

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000307823, ENST00000445895, ENST00000525907, ENST00000529925, ENST00000531040, ENST00000531388, ENST00000531958, ENST00000687366, ENST00000878861, ENST00000878862, ENST00000878863, ENST00000878864, ENST00000963873, ENST00000963874, ENST00000963875, ENST00000963876

RefSeq mRNA: 5 — MANE Select: NM_001166222 NM_001166222, NM_001394577, NM_001394578, NM_001394579, NM_020811

CCDS: CCDS44658, CCDS53667

Canonical transcript exons

ENST00000687366 — 10 exons

Exon	Start	End
ENSE00002161897	67415678	67415763
ENSE00003500883	67419753	67419838
ENSE00003515807	67420939	67421219
ENSE00003560405	67416176	67416202
ENSE00003581541	67420609	67420840
ENSE00003600418	67417407	67417677
ENSE00003627247	67418431	67418520
ENSE00003641541	67419487	67419661
ENSE00003663722	67418756	67419243
ENSE00003928209	67423375	67425604

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 99.72.

FANTOM5 (CAGE): breadth broad, TPM avg 8.8527 / max 1137.1333, expressed in 438 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115456	5.7110	334
115454	1.9677	275
115455	0.9905	130
115462	0.0579	16
206353	0.0569	39
115457	0.0528	28
206354	0.0158	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.72	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.38	gold quality
lateral globus pallidus	UBERON:0002476	99.18	gold quality
subthalamic nucleus	UBERON:0001906	99.03	gold quality
medulla oblongata	UBERON:0001896	98.81	gold quality
spinal cord	UBERON:0002240	98.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.76	gold quality
substantia nigra pars compacta	UBERON:0001965	98.26	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.08	gold quality
superior vestibular nucleus	UBERON:0007227	98.08	gold quality
ventral tegmental area	UBERON:0002691	97.91	gold quality
midbrain	UBERON:0001891	97.13	gold quality
substantia nigra	UBERON:0002038	96.96	gold quality
globus pallidus	UBERON:0001875	96.84	gold quality
medial globus pallidus	UBERON:0002477	96.29	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.97	gold quality
pons	UBERON:0000988	95.94	gold quality
corpus callosum	UBERON:0002336	94.72	gold quality
putamen	UBERON:0001874	94.14	gold quality
postcentral gyrus	UBERON:0002581	94.10	gold quality
Ammon’s horn	UBERON:0001954	94.02	gold quality
parietal lobe	UBERON:0001872	93.99	gold quality
vastus lateralis	UBERON:0001379	93.24	gold quality
quadriceps femoris	UBERON:0001377	92.87	gold quality
amygdala	UBERON:0001876	92.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.88	gold quality
sural nerve	UBERON:0015488	91.53	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.13	gold quality
biceps brachii	UBERON:0001507	90.90	gold quality
caudate nucleus	UBERON:0001873	90.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	54.87
E-GEOD-84465	yes	11.75
E-ANND-3	no	1.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting CARNS1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4505	99.27	67.81	2678

Literature-anchored findings (GeneRIF, showing 3)

• carnosine synthase is identified as ATP-grasp domain-containing protein 1 (PMID:20097752)
• 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)
• Combining bioinformatics analysis and experiments to explore CARNS1 as a prognostic biomarker for breast cancer. (PMID:33533160)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Carns1	ENSMUSG00000075289
rattus_norvegicus	Carns1	ENSRNOG00000018603

Paralogs (2): HAO1 (ENSG00000101323), HAO2 (ENSG00000116882)

Protein

Protein identifiers

Carnosine synthase 1 — A5YM72 (reviewed: A5YM72)

Alternative names: ATP-grasp domain-containing protein 1

All UniProt accessions (1): A5YM72

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine.

Subunit / interactions. Homotetramer.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Isoforms (5)

UniProt ID	Names	Canonical?
A5YM72-1	1	yes
A5YM72-2	2
A5YM72-3	3
A5YM72-4	4
A5YM72-5	5

RefSeq proteins (5): NP_001159694, NP_001381506, NP_001381507, NP_001381508, NP_065862 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011761	ATP-grasp	Domain
IPR031046	CARNS1	Family
IPR041472	BL00235/CARNS1_N	Domain

Pfam: PF15632, PF18130

Enzyme classification (BRENDA):

• EC 6.3.2.11 — carnosine synthase (BRENDA: 6 organisms, 32 substrates, 39 inhibitors, 31 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-AMINOBUTANOATE	0.35–18.2	7
BETA-ALA	1.01–1.8	4
ATP	0.19–0.57	3
BETA-ALANINE	0.033–0.46	3
L-HISTIDINE	0.1–0.37	3
L-LYSINE	1.42–4.67	3
L-ORNITHINE	0.52–7.66	3
N-PI-METHYLHISTIDINE	0.39–24.7	3
L-HIS	0.0166–0.0185	2

Catalyzed reactions (Rhea), 2 shown:

• beta-alanine + L-histidine + ATP = carnosine + ADP + phosphate + H(+) (RHEA:19297)
• 4-aminobutanoate + L-histidine + ATP = L-homocarnosine + ADP + phosphate + H(+) (RHEA:59568)

UniProt features (22 total): binding site 9, sequence conflict 5, splice variant 4, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5YM72-F1	89.10	0.66

Functional residue map

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

Ligand- & substrate-binding residues (9): 691; 542–611; 677; 677; 689; 689; 689; 689; 691

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70921	Histidine catabolism

MSigDB gene sets: 105 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, chr11q13, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, GOMF_ACID_AMINO_ACID_LIGASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON

GO Biological Process (2): L-histidine catabolic process (GO:0006548), carnosine biosynthetic process (GO:0035499)

GO Molecular Function (7): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), metal ion binding (GO:0046872), carnosine synthase activity (GO:0047730), homocarnosine synthase activity (GO:0102102), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acid-amino acid ligase activity	2
aromatic amino acid catabolic process	1
imidazole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
amino acid biosynthetic process	1
carnosine metabolic process	1
carboxylic acid biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARNS1	CNDP1	Q96KN2	779
CARNS1	CARNMT1	Q8N4J0	779
CARNS1	CNDP2	Q96KP4	639
CARNS1	SLC15A2	Q16348	616
CARNS1	SLC6A6	P31641	576
CARNS1	PPP1R18	Q6NYC8	560
CARNS1	SLC15A4	Q8N697	547
CARNS1	SLC15A3	Q8IY34	528
CARNS1	GPR135	Q8IZ08	478
CARNS1	GIMAP8	Q8ND71	460
CARNS1	NPDC1	Q9NQX5	454
CARNS1	COBL	O75128	450
CARNS1	PLLP	Q9Y342	441
CARNS1	PRR15	Q8IV56	432
CARNS1	PARD6B	Q9BYG5	429

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CARNS1	TRIP12	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CARNS1 (Affinity Capture-MS), CARNS1 (Affinity Capture-RNA), CARNS1 (Affinity Capture-MS), TRIP12 (Two-hybrid)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: A5YM72, D3KCC4, Q6ZPS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	176
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1982 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67419196:G:GT	donor_gain	1.0000
11:67419233:A:AG	donor_gain	1.0000
11:67419660:AGGTG:A	donor_loss	1.0000
11:67419662:G:GA	donor_loss	1.0000
11:67419663:T:A	donor_loss	1.0000
11:67420837:CTGG:C	donor_gain	1.0000
11:67420838:TGG:T	donor_gain	1.0000
11:67420839:GG:G	donor_gain	1.0000
11:67420839:GGG:G	donor_gain	1.0000
11:67420840:GG:G	donor_gain	1.0000
11:67420841:G:GG	donor_gain	1.0000
11:67421180:G:GT	donor_gain	1.0000
11:67423363:T:TA	acceptor_gain	1.0000
11:67416199:GATG:G	donor_gain	0.9900
11:67416200:ATGGT:A	donor_loss	0.9900
11:67416201:TGGT:T	donor_loss	0.9900
11:67416202:GGTG:G	donor_loss	0.9900
11:67416203:GTGA:G	donor_loss	0.9900
11:67417653:G:GT	donor_gain	0.9900
11:67419241:CAG:C	donor_loss	0.9900
11:67419242:AG:A	donor_loss	0.9900
11:67419243:GG:G	donor_loss	0.9900
11:67419244:GTAA:G	donor_loss	0.9900
11:67419245:T:A	donor_loss	0.9900
11:67419485:A:T	acceptor_loss	0.9900
11:67419486:GGTA:G	acceptor_gain	0.9900
11:67419662:G:GG	donor_gain	0.9900
11:67419751:AGAT:A	acceptor_gain	0.9900
11:67419752:GAT:G	acceptor_gain	0.9900
11:67419752:GATG:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000104367 (11:67414901 T>A,G), RS1000327470 (11:67417044 T>G), RS1000382916 (11:67416799 G>A,C), RS1000435369 (11:67416637 G>A), RS1000917616 (11:67420696 G>A,T), RS1001711100 (11:67419351 C>T), RS1002214393 (11:67416084 C>T), RS1002427577 (11:67421087 G>A), RS1002921544 (11:67418416 G>A,C,T), RS1003012340 (11:67416075 C>G,T), RS1003092976 (11:67423851 T>C), RS1003216138 (11:67417321 G>A), RS1003238729 (11:67426086 T>C), RS1003374367 (11:67422707 C>T), RS1003427235 (11:67420040 G>C)

Disease associations

OMIM: gene MIM:613368 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21
GCST008163_537	Height	2.000000e-10
GCST90002390_34	Mean corpuscular hemoglobin	4.000000e-28
GCST90002392_350	Mean corpuscular volume	1.000000e-38
GCST90002396_469	Mean reticulocyte volume	7.000000e-43

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	increases expression, decreases expression	2
GSK-J4	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Manganese	increases expression, increases abundance	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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