SLC25A20

protein-coding

solute carrier family 25 member 20, the group of Solute carrier family 25

Gene summary

This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants. [provided by RefSeq, Jul 2008]

Previous symbols:

CACT

MANE transcript

NM_000387.6

Inheritance

ClinVar variants

P:80U:97B:71

Top phenotype

Carnitine-acylcarnitine translocase deficiency

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr3:48,856,926-48,898,904

External References & Databases

Ensembl (ENSG00000178537)

Transcript & Mutation Effects

hg38 • Region Span ~42.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

carnitine-acylcarnitine translocase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: Orphanet

carnitine-acylcarnitine translocase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: ClinGen

carnitine-acylcarnitine translocase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: PanelApp Australia

carnitine-acylcarnitine translocase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: Labcorp Genetics (formerly Invitae)

carnitine-acylcarnitine translocase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: Ambry Genetics

carnitine-acylcarnitine translocase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008918

Submitter: G2P

Clinical Genomic Database (CGD)

Carnitine-acylcarnitine translocase deficiencyAR

Manifestation: Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic

Intervention: Biochemical; Cardiovascular

Rationale: Early recognition and dietary/medical treatment in both the immediate and long-term setting (eg, with IV glucose, dialysis, high-carbohydrate/low-fat diet with frequent feeds and medium-chain triglycerdies, carnitine, or triheptanoin) can be beneficial; Awareness of potential cardiovascular sequelae can allow prompt recognition and management

Refs: 1598097; 7807931; 7564255; 8739960; 9399886; 9323572; 9686371; 9544911; 10384385; 15057979; 15365988; 15363639; 16919490; 17277394; 17508264; 21605995; 24088670; 33610471

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC25A20 variants in ClinVar

7 Conditions Cataloged

Carnitine acylcarnitine translocase deficiencyTotal: 281

not providedTotal: 46

Inborn genetic diseasesTotal: 36

not specifiedTotal: 26

SLC25A20-related disorderTotal: 18

Type 2 diabetes mellitusTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000387.6. 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			3 clinvar	67 clinvar		70
missense	2 clinvar	12 clinvar	94 clinvar	4 clinvar		112
nonsense	9 clinvar	8 clinvar				17
start loss	1 clinvar					1
frameshift	15 clinvar	17 clinvar				32
splice donor/acceptor (+/-2bp)	6 clinvar	10 clinvar				16
Total	33	47	97	71	0	248

Highest pathogenic variant AF is 0.00037915725

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000387.6	RefSeq	NP_000378.1	9	MANE Select
ENST00000319017.5	Ensembl	ENSP00000326305.4	9	MANE Select
ENST00000430379.5	Ensembl	ENSP00000388986.1	7	Standard
ENST00000430379.6	Ensembl	ENSP00000388986.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thermogenesis - Homo sapiens (human)
Beta Oxidation of Very Long Chain Fatty Acids
Oxidation of Branched Chain Fatty Acids
Mitochondrial Beta-Oxidation of Medium Chain Saturated Fatty Acids
Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids

Biological Process

carnitine shuttle
acyl carnitine transmembrane transport

Molecular Function

acyl carnitine transmembrane transporter activity

Cellular Component

mitochondrion
mitochondrial inner membrane
cytosol
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319017
Coding exons: 9
Length: 42058
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.305	152	163	0.933	0.00000935	1940
Missense (PolyPhen)		50	58.864	0.84942		681
Synonymous	0.720	54	61.2	0.883	0.00000323	607
Loss of Function	1.04	13	17.7	0.734	0.00000121	187

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates the transport of acylcarnitines of different length across the mitochondrial inner membrane from the cytosol to the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway.;
Disease: DISEASE: Carnitine-acylcarnitine translocase deficiency (CACTD) [MIM:212138]: A rare long-chain fatty acid oxidation disorder. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long- chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy, arrhythmias, skeletal muscle damage, liver dysfunction and episodes of life-threatening coma, which eventually lead to death. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. {ECO:0000269|PubMed:12859414, ECO:0000269|PubMed:15057979, ECO:0000269|PubMed:15365988}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.228

Intolerance Scores

LoFtool: 0.733
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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