SLC25A1

solute carrier family 25 member 1, the group of Solute carrier family 25

Basic information

Region (hg38): 22:19175581-19178739

Previous symbols: [ "SLC20A3" ]

Links

ENSG00000100075 ∙ NCBI:6576 ∙ OMIM:190315 ∙ HGNC:10979 ∙ Uniprot:P53007 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myasthenic syndrome, congenital, 23, presynaptic (Strong), mode of inheritance: AR
• myasthenic syndrome, congenital, 23, presynaptic (Strong), mode of inheritance: AR
• presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
• D,L-2-hydroxyglutaric aciduria (Supportive), mode of inheritance: AR
• D,L-2-hydroxyglutaric aciduria (Limited), mode of inheritance: AR
• D,L-2-hydroxyglutaric aciduria (Strong), mode of inheritance: AR
• myasthenic syndrome, congenital, 23, presynaptic (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 23, presynaptic	AR	General	Medical management (with 3,4-DAP) has been reported as beneficial	Neurologic	10963100; 23393310; 23561848; 26870663; 31527857; 31808147

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A1 gene.

• not provided (5 variants)
• 2-hydroxyglutaric aciduria (1 variants)
• Inborn genetic diseases (1 variants)
• Myasthenic syndrome, congenital, 23, presynaptic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				35	1	36
missense	1	6	53			60
nonsense	1	1				2
start loss						0
frameshift	4	2				6
inframe indel		1				1
splice donor/acceptor (+/-2bp)	2	1				3
splice region		1	8	11		20
non coding			2	33	10	45
Total	8	11	55	68	11

Highest pathogenic variant AF is 0.0000266

Variants in SLC25A1

This is a list of pathogenic ClinVar variants found in the SLC25A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-19175882-A-AGGCACAGGGTTCACAGTAAGCACATGGACAAGTG			Benign (Feb 28, 2022)
22-19176063-T-TCA			Likely benign (Jun 01, 2021)
22-19176064-C-CAT			Benign (Jun 29, 2018)
22-19176133-G-C			Uncertain significance (Feb 10, 2022)
22-19176136-C-T			Likely benign (Oct 17, 2022)
22-19176137-G-A			Uncertain significance (Aug 31, 2022)
22-19176138-T-C		2-hydroxyglutaric aciduria	Uncertain significance (Feb 17, 2020)
22-19176139-C-T			Benign (Sep 09, 2023)
22-19176154-G-GAGC			Uncertain significance (Sep 16, 2018)
22-19176172-A-G		SLC25A1-related disorder • not specified	Benign/Likely benign (Jul 01, 2024)
22-19176177-A-G		2-hydroxyglutaric aciduria	Uncertain significance (Sep 19, 2018)
22-19176205-G-A			Likely benign (Dec 12, 2023)
22-19176221-C-T		D,L-2-hydroxyglutaric aciduria	Likely pathogenic (Dec 02, 2023)
22-19176222-G-A		2-hydroxyglutaric aciduria • D,L-2-hydroxyglutaric aciduria	Pathogenic/Likely pathogenic (Mar 21, 2023)
22-19176222-G-C		D,L-2-hydroxyglutaric aciduria	Likely pathogenic (Aug 18, 2022)
22-19176225-G-A			Uncertain significance (Aug 22, 2022)
22-19176228-C-T			Uncertain significance (Apr 23, 2021)
22-19176244-T-A			Uncertain significance (Sep 30, 2021)
22-19176257-A-G			Likely benign (Dec 06, 2022)
22-19176262-C-T		not specified	Likely benign (Oct 19, 2022)
22-19176263-G-A			Benign/Likely benign (Nov 15, 2023)
22-19176406-C-T			Likely benign (Nov 29, 2022)
22-19176411-C-G			Likely benign (Aug 23, 2022)
22-19176420-C-T		2-hydroxyglutaric aciduria	Pathogenic (Jul 23, 2019)
22-19176421-G-A		D,L-2-hydroxyglutaric aciduria	Likely pathogenic (Sep 03, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A1	protein_coding	protein_coding	ENST00000215882	9	3249

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0588	0.938	125720	0	24	125744	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	128	174	0.736	0.0000105	1967
Missense in Polyphen		34	53.975	0.62992		555
Synonymous	-1.01	83	72.1	1.15	0.00000428	644
Loss of Function	2.58	5	16.2	0.309	8.80e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000562	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.0000562	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in citrate-H(+)/malate exchange. Important for the bioenergetics of hepatic cells as it provides a carbon source for fatty acid and sterol biosyntheses, and NAD(+) for the glycolytic pathway.
• Disease: DISEASE: Combined D-2- and L-2-hydroxyglutaric aciduria (D2L2AD) [MIM:615182]: An autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts. {ECO:0000269|PubMed:23561848, ECO:0000269|PubMed:27306203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Metabolism of carbohydrates;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Glycolysis and Gluconeogenesis;Metabolism;Fatty acid metabolism;TCA cycle;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.321

Intolerance Scores

• loftool: 0.330
• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

Haploinsufficiency Scores

• pHI: 0.381
• hipred: Y
• hipred_score: 0.760
• ghis: 0.508

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc25a1

Zebrafish Information Network

• Gene name: slc25a1a
• Affected structure: intestine
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: gluconeogenesis;mitochondrial citrate transmembrane transport;fatty-acyl-CoA biosynthetic process
• Cellular component: nucleus;mitochondrial inner membrane;integral component of membrane;extracellular exosome
• Molecular function: citrate transmembrane transporter activity;tricarboxylic acid transmembrane transporter activity