CROT

protein-coding

carnitine O-octanoyltransferase

Gene summary

This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein converts 4,8-dimethylnonanoyl-CoA to its corresponding carnitine ester. This transesterification occurs in the peroxisome and is necessary for transport of medium- and long- chain acyl-CoA molecules out of the peroxisome to the cytosol and mitochondria. The protein thus plays a role in lipid metabolism and fatty acid beta-oxidation. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]

MANE transcript

NM_021151.4

Inheritance

—

ClinVar variants

U:101B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr7:87,345,664-87,399,794

External References & Databases

Ensembl (ENSG00000005469)

Transcript & Mutation Effects

hg38 • Region Span ~54.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CROT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021151.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar			4
missense			93 clinvar	5 clinvar	1 clinvar	99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	101	5	1	107

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021151.4	RefSeq	NP_066974.2	16	MANE Select
ENST00000331536.8	Ensembl	ENSP00000331981.4	16	MANE Select
NM_001143935.2	RefSeq	NP_001137407.1	17	Standard
NM_001243745.3	RefSeq	NP_001230674.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peroxisome - Homo sapiens (human)
Beta Oxidation of Very Long Chain Fatty Acids
Oxidation of Branched Chain Fatty Acids
Adrenoleukodystrophy, X-linked
Carnitine-acylcarnitine translocase deficiency

Biological Process

generation of precursor metabolites and energy
protein targeting to peroxisome
fatty acid metabolic process
fatty acid beta-oxidation
carnitine metabolic process

Molecular Function

signaling receptor binding
carnitine O-octanoyltransferase activity

Cellular Component

peroxisome
peroxisomal matrix
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000419147
Coding exons: 17
Length: 54115
Individuals with no LoFs: 125122
Homozygous LoFs: 2
Heterozygous LoFs: 623
Defined: 125747
p: 0.00249

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00457	342	342	0.999	0.0000175	4182
Missense (PolyPhen)		116	118.64	0.97772		1409
Synonymous	0.807	104	115	0.904	0.00000573	1181
Loss of Function	0.612	40	44.4	0.901	0.00000274	481

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0040	0.0038	notable
Latino/Admixed American	0.0019	0.0019	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0.0036	0.0036	notable
European (Non-Finnish)	0.0029	0.0028	notable
South Asian	0.0028	0.0027	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. Converts the end product of pristanic acid beta oxidation, 4,8-dimethylnonanoyl- CoA, to its corresponding carnitine ester. {ECO:0000269|PubMed:10486279}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.113
RVIS EVS: -0.37
RVIS percentile EVS: 28.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.130

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium