SLC25A20

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

Basic information

Region (hg38): 3:48856926-48898904

Previous symbols: [ "CACT" ]

Links

ENSG00000178537 ∙ NCBI:788 ∙ OMIM:613698 ∙ HGNC:1421 ∙ Uniprot:O43772 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• carnitine-acylcarnitine translocase deficiency (Definitive), mode of inheritance: AR
• carnitine-acylcarnitine translocase deficiency (Strong), mode of inheritance: AR
• carnitine-acylcarnitine translocase deficiency (Strong), mode of inheritance: AR
• carnitine-acylcarnitine translocase deficiency (Definitive), mode of inheritance: AR
• carnitine-acylcarnitine translocase deficiency (Supportive), mode of inheritance: AR
• carnitine-acylcarnitine translocase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carnitine-acylcarnitine translocase deficiency	AR	Biochemical; Cardiovascular	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	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	1598097; 7807931; 7564255; 8739960; 9399886; 9323572; 9686371; 9544911; 10384385; 15057979; 15365988; 15363639; 16919490; 17277394; 17508264; 21605995; 24088670; 33610471

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A20 gene.

• Carnitine_acylcarnitine_translocase_deficiency (267 variants)
• not_provided (39 variants)
• Inborn_genetic_diseases (30 variants)
• not_specified (20 variants)
• SLC25A20-related_disorder (11 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A20 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000387.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	62		64
missense	2	11	87	2		102
nonsense	8	8				16
start loss	1					1
frameshift	16	15				31
splice donor/acceptor (+/-2bp)	6	10				16
Total	33	44	89	64	0

Highest pathogenic variant AF is 0.000055789456

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A20	protein_coding	protein_coding	ENST00000319017	9	42058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.20e-7	0.580	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.305	152	163	0.933	0.00000935	1940
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000789	0.000789
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000178	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;Adrenoleukodystrophy, X-linked;Carnitine-acylcarnitine translocase deficiency;Fatty Acid Beta Oxidation;Mitochondrial LC-Fatty Acid Beta-Oxidation;Liver steatosis AOP;Metabolism of lipids;Import of palmitoyl-CoA into the mitochondrial matrix;Saturated fatty acids beta-oxidation;Metabolism;Fatty acid metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.733
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.457
• hipred: N
• hipred_score: 0.466
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.925

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc25a20
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; liver/biliary system phenotype; embryo phenotype

Gene ontology

• Biological process: carnitine shuttle;acyl carnitine transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;cytosol;integral component of membrane
• Molecular function: acyl carnitine transmembrane transporter activity