CRAT

protein-coding

carnitine O-acetyltransferase

Gene summary

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. [provided by RefSeq, Oct 2016]

MANE transcript

NM_000755.5

Inheritance

ClinVar variants

P:2U:226B:78

Top phenotype

Neurodegeneration with brain iron accumulation 8

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr9:129,094,142-129,111,189

External References & Databases

Ensembl (ENSG00000095321)

Transcript & Mutation Effects

hg38 • Region Span ~17.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegeneration with brain iron accumulation 8LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054764

Submitter: Ambry Genetics

neurodegeneration with brain iron accumulation 8LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054764

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Neurodegeneration with brain iron accumulation 8AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29395073

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRAT variants in ClinVar

7 Conditions Cataloged

not providedTotal: 295

not specifiedTotal: 99

Neurodegeneration with brain iron accumulation 8Total: 15

CRAT-related disorderTotal: 8

Deficiency of carnitine acetyltransferaseTotal: 3

Neurodegeneration with brain iron accumulationTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000755.5. 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			2 clinvar	63 clinvar	6 clinvar	71
missense		1 clinvar	203 clinvar	6 clinvar	3 clinvar	213
nonsense			4 clinvar			4
start loss			1 clinvar			1
frameshift		1 clinvar	7 clinvar			8
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	2	226	69	9	306

Highest pathogenic variant AF is 0.000016735012

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 101 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000755.5	RefSeq	NP_000746.3	14	MANE Select
ENST00000318080.7	Ensembl	ENSP00000315013.2	14	MANE Select
NM_001257363.3	RefSeq	NP_001244292.2	13	Standard
NM_001346546.2	RefSeq	NP_001333475.2	14	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

protein targeting to peroxisome
carnitine metabolic process, CoA-linked
fatty acid beta-oxidation using acyl-CoA oxidase

Molecular Function

carnitine O-acetyltransferase activity
signaling receptor binding

Cellular Component

mitochondrion
mitochondrial inner membrane
peroxisome
peroxisomal matrix
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318080
Coding exons: 14
Length: 16380
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 75
Defined: 125748
p: 0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.852	354	402	0.880	0.0000260	4097
Missense (PolyPhen)		105	133.94	0.78395		1421
Synonymous	0.578	160	170	0.944	0.0000117	1225
Loss of Function	1.59	22	31.6	0.696	0.00000160	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00085	0.00085	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. May be specific for short chain fatty acids. {ECO:0000305|PubMed:29395073}.;

Recessive Scores

pRec: 0.509

Intolerance Scores

LoFtool: 0.189
RVIS EVS: -1.08
RVIS percentile EVS: 7.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.151

Gene Damage Prediction

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