CRAT

Summary

CRAT (carnitine O-acetyltransferase, HGNC:2342) is a protein-coding gene on chromosome 9q34.11, encoding Carnitine O-acetyltransferase (P43155). Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio.

This gene encodes carnitine O-acetyltransferase, a member of the carnitine acyltransferase family and a key metabolic pathway enzyme which plays an important role in energy homeostasis and fat metabolism. This enzyme catalyzes the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of acyl-CoA/CoA. It is found in both the mitochondria and the peroxisome. Alternative splicing results in transcript variants encoding different isoforms that may localize to different subcellular compartments.

Source: NCBI Gene 1384 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration with brain iron accumulation 8 (Limited, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 365 total — 1 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes
• MANE Select transcript: NM_000755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2342
Approved symbol	CRAT
Name	carnitine O-acetyltransferase
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	CAT1
Ensembl gene	ENSG00000095321
Ensembl biotype	protein_coding
OMIM	600184
Entrez	1384

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 27 protein_coding, 9 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000318080, ENST00000393384, ENST00000415948, ENST00000441796, ENST00000455396, ENST00000455830, ENST00000458362, ENST00000464290, ENST00000467343, ENST00000679520, ENST00000679716, ENST00000680093, ENST00000680117, ENST00000680523, ENST00000681040, ENST00000681118, ENST00000681325, ENST00000681622, ENST00000681627, ENST00000681689, ENST00000681725, ENST00000681911, ENST00000868874, ENST00000868875, ENST00000868876, ENST00000868877, ENST00000868878, ENST00000868879, ENST00000943957, ENST00000943958, ENST00000943959, ENST00000943960, ENST00000943961, ENST00000943962, ENST00000943963, ENST00000943964, ENST00000943965, ENST00000943966, ENST00000943967, ENST00000943968, ENST00000943969

RefSeq mRNA: 7 — MANE Select: NM_000755 NM_000755, NM_001257363, NM_001346546, NM_001346547, NM_001346548, NM_001346549, NM_004003

CCDS: CCDS6919, CCDS94505, CCDS94506

Canonical transcript exons

ENST00000318080 — 14 exons

Exon	Start	End
ENSE00001821873	129094794	129095612
ENSE00002261527	129110483	129110793
ENSE00003486223	129101883	129102057
ENSE00003494978	129099866	129099966
ENSE00003500355	129098013	129098148
ENSE00003534601	129100511	129100689
ENSE00003538641	129098531	129098650
ENSE00003551585	129097250	129097312
ENSE00003595681	129103013	129103066
ENSE00003620580	129104188	129104306
ENSE00003623438	129098249	129098371
ENSE00003635200	129095998	129096135
ENSE00003653857	129102400	129102565
ENSE00003785611	129107814	129108077

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2746 / max 414.9982, expressed in 1710 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102728	19.0545	1655
102731	0.0533	31
102725	0.0457	20
102723	0.0304	12
102726	0.0286	12
102727	0.0255	11
102729	0.0216	8
102730	0.0149	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.58	gold quality
male germ cell	CL:0000015	99.21	gold quality
left testis	UBERON:0004533	98.62	gold quality
right testis	UBERON:0004534	98.45	gold quality
upper leg skin	UBERON:0004262	98.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.04	gold quality
gastrocnemius	UBERON:0001388	97.77	gold quality
pancreatic ductal cell	CL:0002079	97.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.68	gold quality
right lobe of liver	UBERON:0001114	97.37	gold quality
muscle of leg	UBERON:0001383	97.27	gold quality
diaphragm	UBERON:0001103	97.26	gold quality
vastus lateralis	UBERON:0001379	97.17	gold quality
muscle organ	UBERON:0001630	97.00	gold quality
apex of heart	UBERON:0002098	96.90	gold quality
body of pancreas	UBERON:0001150	96.87	gold quality
testis	UBERON:0000473	96.75	gold quality
adult organism	UBERON:0007023	96.70	gold quality
quadriceps femoris	UBERON:0001377	96.51	gold quality
upper arm skin	UBERON:0004263	96.34	gold quality
skeletal muscle tissue	UBERON:0001134	96.28	gold quality
liver	UBERON:0002107	96.27	gold quality
mammalian vulva	UBERON:0000997	95.95	gold quality
cervix squamous epithelium	UBERON:0006922	95.93	silver quality
triceps brachii	UBERON:0001509	95.53	gold quality
body of tongue	UBERON:0011876	95.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.18	gold quality
duodenum	UBERON:0002114	94.94	gold quality
right adrenal gland	UBERON:0001233	94.88	gold quality
muscle tissue	UBERON:0002385	94.73	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, MYC

miRNA regulators (miRDB)

25 targeting CRAT, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-132-5P	96.61	65.79	115
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-10392-3P	88.79	61.83	122

Literature-anchored findings (GeneRIF, showing 10)

• Human CPT1A, CPT1B, CPT2, CROT and CRAT are known to encode active carnitine acyltransferases. Earlier pfam annotations refer to the non-existing compound CARNITATE. In 2000 this has been changed to CARNITINE. (PMID:11001805)
• the purification, crystallization and preliminary X-ray crystallographic studies of human carnitine acetyltransferase are reported (PMID:12077440)
• The structure and reactions of this enzyme are examined. (PMID:12562770)
• structure of a binary complex of human peroxisomal carnitine acetyltransferase and the substrate l-carnitine, refined to a resolution of 1.8; site-directed mutagenesis and kinetic characterization (PMID:15099582)
• Data show that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. (PMID:19553674)
• CrAT turned out to be active towards some but not all the BCAAO intermediates tested and no activity was found with dicarboxylic acyl-CoA esters. (PMID:23485643)
• We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. (PMID:28671672)
• CRAT missense variants cause abnormal carnitine acetyltransferase function in an early-onset case of Leigh syndrome. (PMID:31448845)
• Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans. (PMID:36413408)
• Carnitine acetyltransferase deficiency mediates mitochondrial dysfunction-induced cellular senescence in dermal fibroblasts. (PMID:37828898)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	CRAT	ENSDARG00000016545
danio_rerio	crata	ENSDARG00000040248
mus_musculus	Crat	ENSMUSG00000026853
rattus_norvegicus	Crat	ENSRNOG00000018145
drosophila_melanogaster	CG5122	FBGN0032471
drosophila_melanogaster	CRAT	FBGN0037440
drosophila_melanogaster	CG5265	FBGN0038486
caenorhabditis_elegans		WBGENE00007175

Paralogs (6): CROT (ENSG00000005469), CHAT (ENSG00000070748), CPT1A (ENSG00000110090), CPT2 (ENSG00000157184), CPT1C (ENSG00000169169), CPT1B (ENSG00000205560)

Protein

Protein identifiers

Carnitine O-acetyltransferase — P43155 (reviewed: P43155)

Alternative names: Carnitine acetyltransferase

All UniProt accessions (10): P43155, A0A7P0T9E7, A0A7P0T9R9, A0A7P0TAQ4, A0A7P0TAR1, A0A7P0TBF3, A6PVN3, B7ZBP5, F2Z2C5, H0Y4Z7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio. Also plays a crucial role in the transport of fatty acids for beta-oxidation. Responsible for the synthesis of short- and branched-chain acylcarnitines. Active towards some branched-chain amino acid oxidation pathway (BCAAO) intermediates. Trans-2-enoyl-CoAs and 2-methylacyl-CoAs are poor substrates.

Subunit / interactions. Monomer.

Subcellular location. Endoplasmic reticulum. Peroxisome. Mitochondrion inner membrane Mitochondrion Peroxisome.

Tissue specificity. Mostly in skeletal muscle, less in heart, liver and pancreas, only weakly detectable in brain, placenta, lung and kidney.

Disease relevance. Neurodegeneration with brain iron accumulation 8 (NBIA8) [MIM:617917] A neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. Disease onset is in early childhood. Clinical features include speech delay, progressive cerebellar ataxia, unbalanced gait, and loss of ambulation. NBIA8 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the carnitine/choline acetyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P43155-1	1, SM-1400	yes
P43155-2	2, SM-1200
P43155-3	3

RefSeq proteins (7): NP_000746, NP_001244292, NP_001333475, NP_001333476, NP_001333477, NP_001333478, NP_003994 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000542	Carn_acyl_trans	Family
IPR023213	CAT-like_dom_sf	Homologous_superfamily
IPR039551	Cho/carn_acyl_trans_1_2	Domain
IPR042231	Cho/carn_acyl_trans_2	Homologous_superfamily

Pfam: PF00755

Enzyme classification (BRENDA):

• EC 2.3.1.7 — carnitine O-acetyltransferase (BRENDA: 20 organisms, 99 substrates, 83 inhibitors, 179 Km, 28 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETYL-COA	0.012–0.498	31
CARNITINE	0.0035–300	27
COASH	0.009–2	25
L-CARNITINE	0.1–35.9	16
BUTYRYL-COA	0.015–0.499	8
HEXANOYL-COA	0.02–0.112	8
PROPIONYL-COA	0.014–0.185	8
ACETYLCARNITINE	0.019–0.639	7
CHOLINE	1.1–86.4	6
L-(-)-CARNITINE	0.039–0.244	6
COA	0.0063–0.1134	5
OCTANOYL-COA	0.011–0.0503	4
OCTANOYLCARNITINE	1.27–1.62	3
BUTYRYLCARNITINE	0.48–0.66	2
DECANOYL-COA	0.0287–0.064	2

Catalyzed reactions (Rhea), 12 shown:

• octanoyl-CoA + (R)-carnitine = O-octanoyl-(R)-carnitine + CoA (RHEA:17177)
• (R)-carnitine + acetyl-CoA = O-acetyl-(R)-carnitine + CoA (RHEA:21136)
• decanoyl-CoA + (R)-carnitine = O-decanoyl-(R)-carnitine + CoA (RHEA:44828)
• 4,8-dimethylnonanoyl-CoA + (R)-carnitine = O-4,8-dimethylnonanoyl-(R)-carnitine + CoA (RHEA:44860)
• hexanoyl-CoA + (R)-carnitine = O-hexanoyl-(R)-carnitine + CoA (RHEA:44972)
• propanoyl-CoA + (R)-carnitine = O-propanoyl-(R)-carnitine + CoA (RHEA:44976)
• butanoyl-CoA + (R)-carnitine = O-butanoyl-(R)-carnitine + CoA (RHEA:44980)
• 3-methylbutanoyl-CoA + (R)-carnitine = O-3-methylbutanoyl-(R)-carnitine + CoA (RHEA:44984)
• 2-methylpropanoyl-CoA + (R)-carnitine = O-isobutanoyl-(R)-carnitine + CoA (RHEA:44988)
• 2-methylbutanoyl-CoA + (R)-carnitine = O-2-methylbutanoyl-(R)-carnitine + CoA (RHEA:44992)
• acetoacetyl-CoA + (R)-carnitine = O-3-oxobutanoyl-(R)-carnitine + CoA (RHEA:44996)
• 3-hydroxybutanoyl-CoA + (R)-carnitine = O-3-hydroxybutanoyl-(R)-carnitine + CoA (RHEA:45000)

UniProt features (76 total): helix 21, strand 21, binding site 8, mutagenesis site 6, modified residue 4, sequence conflict 4, turn 4, sequence variant 3, splice variant 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9SCK	X-RAY DIFFRACTION	1.4
1NM8	X-RAY DIFFRACTION	1.6
1S5O	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43155-F1	94.75	0.92

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 (1): 343 (proton acceptor)

Ligand- & substrate-binding residues (8): 555; 419; 423–430; 452; 454; 456; 465; 504

Post-translational modifications (4): 93, 261, 261, 268

Mutagenesis-validated functional residues (6):

Position	Phenotype
452	increases the km for carnitine 100-fold.
452	increases the km for carnitine 320-fold and reduces enzyme activity 10000-fold.
465	increases the km for carnitine almost 70-fold and reduces enzyme activity 450-fold.
518	increases the km for carnitine 230-fold and reduces enzyme activity almost 100-fold.
566	increases the km for carnitine 18-fold and reduces enzyme activity 100-fold.
566	no effect.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-389887	Beta-oxidation of pristanoyl-CoA
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-9033241	Peroxisomal protein import
R-HSA-1430728	Metabolism
R-HSA-390918	Peroxisomal lipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9609507	Protein localization

MSigDB gene sets: 221 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GRUETZMANN_PANCREATIC_CANCER_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, AAAYRNCTG_UNKNOWN, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GTGCCTT_MIR506, GOBP_FATTY_ACID_BETA_OXIDATION_USING_ACYL_COA_OXIDASE, GOBP_SHORT_CHAIN_FATTY_ACID_METABOLIC_PROCESS, KMCATNNWGGA_UNKNOWN

GO Biological Process (7): carnitine metabolic process, CoA-linked (GO:0019254), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), short-chain fatty acid metabolic process (GO:0046459), medium-chain fatty acid metabolic process (GO:0051791), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid beta-oxidation (GO:0006635)

GO Molecular Function (6): acyl-CoA oxidase activity (GO:0003997), carnitine O-acetyltransferase activity (GO:0004092), carnitine O-octanoyltransferase activity (GO:0008458), O-acetyltransferase activity (GO:0016413), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Peroxisomal lipid metabolism	1
Metabolism of amino acids and derivatives	1
Protein localization	1
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
fatty acid metabolic process	2
carnitine O-acyltransferase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
carnitine metabolic process	1
fatty acid beta-oxidation	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor	1
O-acetyltransferase activity	1
acetyltransferase activity	1
catalytic activity	1
transferase activity	1
organelle inner membrane	1
mitochondrial membrane	1
microbody	1
peroxisome	1
microbody lumen	1
endomembrane system	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRAT	SLC25A20	O43772	760
CRAT	EHHADH	Q08426	615
CRAT	CS	O75390	569
CRAT	ACSS2	Q9NR19	557
CRAT	ACSS1	Q9NUB1	533
CRAT	HSD17B4	P51659	530
CRAT	ACHE	P22303	506
CRAT	ACOX1	Q15067	493
CRAT	ACLY	P53396	486
CRAT	HADHB	P55084	479
CRAT	ACOT12	Q8WYK0	475
CRAT	ECH1	Q13011	467
CRAT	SLC22A5	O76082	460
CRAT	HADH	Q16836	454
CRAT	ACADL	P28330	448

IntAct

50 interactions, top by confidence:

A	B	Type	Score
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
RGS3	ZNF24	psi-mi:“MI:0914”(association)	0.530
NS1	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CRAT	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
METAP1D	CRAT	psi-mi:“MI:0915”(physical association)	0.400
CRAT	MLF1	psi-mi:“MI:0915”(physical association)	0.400
CRAT	MLF2	psi-mi:“MI:0915”(physical association)	0.400
CRAT	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
	CRAT	psi-mi:“MI:0915”(physical association)	0.400
CACYBP	CRAT	psi-mi:“MI:0915”(physical association)	0.400
AARSD1	CRAT	psi-mi:“MI:0915”(physical association)	0.400
CRAT	PPP5C	psi-mi:“MI:0915”(physical association)	0.400
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
PFDN5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
COX4I1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
RGS3	ZNF646	psi-mi:“MI:0914”(association)	0.350
HINT2	CST4	psi-mi:“MI:0914”(association)	0.350
CRAT	SMAD4	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
TRMU	IFT56	psi-mi:“MI:0914”(association)	0.350
MRM2	VWA8	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
ACSM5	VWA8	psi-mi:“MI:0914”(association)	0.350
RASL10B	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): CRAT (Affinity Capture-MS), CRAT (Affinity Capture-MS), CRAT (Affinity Capture-MS), ACOX1 (Co-fractionation), CRAT (Co-fractionation), CRAT (Co-fractionation), SPTBN1 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Proximity Label-MS), CRAT (Affinity Capture-MS)

ESM2 similar proteins: A2RTX5, A2Z8S0, B2ZGJ1, F1LN46, O19094, P07668, P11035, P11466, P13222, P17569, P18886, P23786, P28329, P32198, P32738, P32756, P32796, P36859, P43155, P47934, P49696, P50416, P52825, P52826, P56523, P80235, P97742, Q03059, Q0V9S0, Q2KJB7, Q58DK1, Q5U3U3, Q60HG9, Q63704, Q68Y62, Q6P4X5, Q704S8, Q75G68, Q7ZXE1, Q80VY9

Diamond homologs: B2ZGJ1, O19094, P07668, P11466, P13222, P28329, P32738, P32756, P32796, P43155, P47934, P52826, Q03059, Q704S8, Q90YJ9, Q9DC50, P18886, P32198, P52825, Q9UKG9, P50416, P97742, Q8HY46, Q92523, Q68Y62, P23786, P80235, Q2KJB7, Q5U3U3, Q60HG9, Q6P4X5, Q7ZXE1, Q58DK1, Q63704, F1LN46, Q924X2, Q8BGD5, Q8TCG5, Q00614

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	230
Likely benign	103
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4845764	NM_000755.5(CRAT):c.495del (p.Lys166fs)	Likely pathogenic

SpliceAI

2589 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129095571:C:CT	acceptor_gain	1.0000
9:129095611:ACCTG:A	acceptor_loss	1.0000
9:129095613:C:CC	acceptor_gain	1.0000
9:129095613:CTGGG:C	acceptor_loss	1.0000
9:129095993:CCCA:C	donor_loss	1.0000
9:129095994:CCA:C	donor_loss	1.0000
9:129095995:CACC:C	donor_loss	1.0000
9:129095996:A:T	donor_loss	1.0000
9:129095997:C:CA	donor_loss	1.0000
9:129095997:CCTGG:C	donor_gain	1.0000
9:129096131:ATGGC:A	acceptor_gain	1.0000
9:129096132:TGGC:T	acceptor_gain	1.0000
9:129096133:GGC:G	acceptor_gain	1.0000
9:129096134:GC:G	acceptor_gain	1.0000
9:129096134:GCCTG:G	acceptor_loss	1.0000
9:129096135:CC:C	acceptor_gain	1.0000
9:129096136:C:A	acceptor_loss	1.0000
9:129096136:C:CC	acceptor_gain	1.0000
9:129096139:T:TC	acceptor_gain	1.0000
9:129097246:TTAC:T	donor_loss	1.0000
9:129097247:TACC:T	donor_loss	1.0000
9:129097248:A:AC	donor_gain	1.0000
9:129097248:AC:A	donor_gain	1.0000
9:129097248:ACCCG:A	donor_loss	1.0000
9:129097249:C:CC	donor_gain	1.0000
9:129097249:CC:C	donor_gain	1.0000
9:129097249:CCCGG:C	donor_gain	1.0000
9:129097310:CTC:C	acceptor_gain	1.0000
9:129097313:C:CC	acceptor_gain	1.0000
9:129097313:C:CG	acceptor_loss	1.0000

AlphaMissense

4128 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129098097:A:C	F460L	0.999
9:129098097:A:T	F460L	0.999
9:129098099:A:G	F460L	0.999
9:129100531:A:G	W322R	0.999
9:129100531:A:T	W322R	0.999
9:129096084:C:G	A527P	0.998
9:129098113:G:T	A455D	0.998
9:129098115:A:C	S454R	0.998
9:129098115:A:T	S454R	0.998
9:129098117:T:G	S454R	0.998
9:129100533:C:G	R321P	0.998
9:129100534:G:T	R321S	0.998
9:129101922:G:T	R256S	0.998
9:129101990:A:G	L233P	0.998
9:129102468:C:G	D188H	0.998
9:129102488:C:G	R181P	0.998
9:129104241:G:C	S119R	0.998
9:129104241:G:T	S119R	0.998
9:129104243:T:G	S119R	0.998
9:129096001:G:C	S554R	0.997
9:129096001:G:T	S554R	0.997
9:129096003:T:G	S554R	0.997
9:129096095:A:G	L523P	0.997
9:129096098:C:T	G522D	0.997
9:129098086:C:G	R464P	0.997
9:129098087:G:T	R464S	0.997
9:129098089:C:A	G463V	0.997
9:129098089:C:T	G463D	0.997
9:129098090:C:G	G463R	0.997
9:129098104:C:G	R458P	0.997

dbSNP variants (sampled 300 via entrez): RS1000015998 (9:129110230 CT>C), RS1000387986 (9:129106051 CGTG>C), RS1001043969 (9:129095865 G>A), RS1001104761 (9:129103971 C>G), RS1001349921 (9:129106976 G>C), RS1001360175 (9:129097479 C>G,T), RS1001461380 (9:129110648 C>A,T), RS1001623655 (9:129101708 G>A), RS1002046148 (9:129097453 A>G), RS1002105378 (9:129096743 C>T), RS1002329079 (9:129103599 T>A), RS1002481731 (9:129109851 G>T), RS1002664776 (9:129102239 C>G,T), RS1003044412 (9:129098751 G>A,C,T), RS1003178307 (9:129103913 T>C)

Disease associations

OMIM: gene MIM:600184 | disease phenotypes: MIM:617917, MIM:234200, MIM:606175

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration with brain iron accumulation 8	Limited	Autosomal recessive

Mondo (3): neurodegeneration with brain iron accumulation 8 (MONDO:0054764), neurodegeneration with brain iron accumulation (MONDO:0018307), carnitine acetyltransferase deficiency (MONDO:0011642)

Orphanet (1): Neurodegeneration with brain iron accumulation (Orphanet:385)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000750	Delayed speech and language development
HP:0000763	Sensory neuropathy
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0002151	Increased circulating lactate concentration
HP:0002317	Unsteady gait
HP:0002505	Loss of ambulation
HP:0003676	Progressive
HP:0011463	Childhood onset
HP:0012675	Iron accumulation in brain

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003225_3	Pelvic organ prolapse (moderate/severe)	2.000000e-06
GCST004621_130	Red cell distribution width	4.000000e-22
GCST006804_103	Red cell distribution width	4.000000e-20
GCST006879_1	Blood metabolite levels	1.000000e-09
GCST006879_18	Blood metabolite levels	3.000000e-43
GCST006879_19	Blood metabolite levels	4.000000e-83
GCST006879_2	Blood metabolite levels	2.000000e-12
GCST006879_20	Blood metabolite levels	5.000000e-12
GCST006879_21	Blood metabolite levels	2.000000e-22
GCST006879_22	Blood metabolite levels	2.000000e-20
GCST007191_1	Hypersomnia (HLA-DQB1*06:02 negative)	8.000000e-09
GCST010143_23	Meat-related diet	6.000000e-11
GCST012020_408	Serum metabolite levels	2.000000e-19
GCST90002403_619	Red blood cell count	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0008111	diet measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563249	Carnitine Acetyltransferase Deficiency (supp.)
C538421	Neurodegeneration with brain iron accumulation (NBIA) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3184 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	3
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
quinone	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Carmustine	decreases expression	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Potassium Dichromate	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL660926	Binding	Tested against pigeon breast carnitine acyltransferase	3-Amino-5,5-dimethylhexanoic acid. Synthesis, resolution, and effects on carnitine acyltransferases. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2V7	Abcam HEK293T CRAT KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02587858	Not specified	UNKNOWN	NBIAready: Online Collection of Natural History Patient-reported Outcome Measures
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry
NCT05615571	Not specified	COMPLETED	Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT06596746	Not specified	RECRUITING	Neurodegenerative Diseases Progression Markers (MARKERS-NDD)