SLC25A13

solute carrier family 25 member 13, the group of EF-hand domain containing|Solute carrier family 25|MicroRNA protein coding host genes

Basic information

Region (hg38): 7:96120219-96322147

Previous symbols: [ "CTLN2" ]

Links

ENSG00000004864 ∙ NCBI:10165 ∙ OMIM:603859 ∙ HGNC:10983 ∙ Uniprot:Q9UJS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• citrullinemia type II (Supportive), mode of inheritance: AR
• neonatal intrahepatic cholestasis due to citrin deficiency (Supportive), mode of inheritance: AR
• citrullinemia, type II, adult-onset (Strong), mode of inheritance: AR
• citrin deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Citrin deficiency	AR	Biochemical; Oncologic	Dietary (galactose-free diet) and pharmacotherapy (eg, sodium benzoate, sodium phenylbutyrate, and arginine) can be beneficial; Individuals may be at increased risk of hepatocellular carcinoma, and awareness may allow preventive measures, early detection, and treatment; Liver transplantation can be effective	Biochemical; Gastrointestinal; Hematologic; Neurologic; Oncologic	10369257; 11153906; 11281457; 11343052; 11343053; 17323144; 18367750; 12111366; 20301360; 21161389; 21424115; 21914561; 22710133; 22277121; 22892490; 23053473; 23067347; 23112554; 25135652
The adult-onset form may present after the pediatric interval

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A13 gene.

• Citrin deficiency (521 variants)
• not provided (138 variants)
• Citrullinemia, type II, adult-onset (88 variants)
• Citrullinemia type II (83 variants)
• Citrullinemia type I (41 variants)
• Neonatal intrahepatic cholestasis due to citrin deficiency (38 variants)
• Citrullinemia (36 variants)
• not specified (28 variants)
• Inborn genetic diseases (22 variants)
• Late-onset citrullinemia (20 variants)
• SLC25A13-related condition (8 variants)
• Citrullinemia, type II, adult-onset;Neonatal intrahepatic cholestasis due to citrin deficiency (6 variants)
• Neonatal intrahepatic cholestasis due to citrin deficiency;Citrullinemia, type II, adult-onset (4 variants)
• - (2 variants)
• Citrullinemia type II;Neonatal intrahepatic cholestasis due to citrin deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A13 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			3	189	5	197
missense	2	15	112	4		133
nonsense	24	15	1			40
start loss			3			3
frameshift	32	22	2			56
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	9	24				33
splice region	3	4	10	34	5	56
non coding			22	85	21	128
Total	67	77	144	278	26

Highest pathogenic variant AF is 0.000197

Variants in SLC25A13

This is a list of pathogenic ClinVar variants found in the SLC25A13 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-96120282-G-C		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 13, 2018)
7-96120310-A-C		Citrullinemia type II	Uncertain significance (Jan 13, 2018)
7-96120399-G-A		Citrullinemia type I • Citrullinemia type II	Conflicting classifications of pathogenicity (Jan 13, 2018)
7-96120441-A-G		Citrullinemia type II	Uncertain significance (Jan 12, 2018)
7-96120462-C-T		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 13, 2018)
7-96120506-GCTACAT-G			Likely benign (May 16, 2021)
7-96120569-G-A		Citrullinemia type II	Uncertain significance (Jan 13, 2018)
7-96120621-C-T		Citrullinemia type I • Citrullinemia type II	Conflicting classifications of pathogenicity (Jan 12, 2018)
7-96120674-T-C		Citrullinemia type I • Citrullinemia type II	Uncertain significance (Jan 13, 2018)
7-96120684-A-G		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 12, 2018)
7-96120861-C-A		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 13, 2018)
7-96120881-G-A		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 12, 2018)
7-96120911-C-A		Citrullinemia type II	Uncertain significance (Jan 12, 2018)
7-96121000-A-G		Citrullinemia type II • Citrullinemia type I	Uncertain significance (Jan 12, 2018)
7-96121016-T-C		Citrullinemia type II • Citrullinemia type I	Benign/Likely benign (Sep 14, 2019)
7-96121098-C-T		Citrullinemia type II	Uncertain significance (Jan 13, 2018)
7-96121119-C-T		Citrullinemia type I • Citrullinemia type II	Uncertain significance (Jan 13, 2018)
7-96121151-G-A		Citrullinemia type II	Uncertain significance (Jan 12, 2018)
7-96121193-A-G		Citrin deficiency	Uncertain significance (May 21, 2022)
7-96121206-A-G		Citrin deficiency	Likely benign (Dec 23, 2021)
7-96121215-T-C		Citrin deficiency	Likely benign (Dec 05, 2023)
7-96121221-A-G		Citrin deficiency	Likely benign (Mar 27, 2022)
7-96121224-T-C		Citrin deficiency	Likely benign (Dec 20, 2022)
7-96121233-C-T		Citrin deficiency	Likely benign (Apr 20, 2020)
7-96121236-G-A		Citrin deficiency	Likely benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A13	protein_coding	protein_coding	ENST00000416240	18	201928

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-24	0.00109	125495	1	252	125748	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.305	348	364	0.955	0.0000201	4365
Missense in Polyphen		93	106.88	0.87017		1290
Synonymous	0.217	127	130	0.976	0.00000715	1363
Loss of Function	0.329	38	40.3	0.944	0.00000244	450

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000682	0.000681
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00691	0.00693
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000654	0.000642
Middle Eastern	0.00691	0.00693
South Asian	0.000949	0.000948
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial and calcium-binding carrier that catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane (PubMed:11566871, PubMed:25410934). May have a function in the urea cycle (PubMed:11566871). {ECO:0000269|PubMed:11566871, ECO:0000269|PubMed:25410934}.
• Disease: DISEASE: Citrullinemia 2 (CTLN2) [MIM:603471]: A form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. Citrullinemia type 2 is characterized by neuropsychiatric symptoms including abnormal behaviors, loss of memory, seizures and coma. Death can result from brain edema. Onset is sudden and usually between the ages of 20 and 50 years. {ECO:0000269|PubMed:10369257, ECO:0000269|PubMed:10610724}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cholestasis, neonatal intrahepatic, caused by citrin deficiency (NICCD) [MIM:605814]: A form of citrullinemia type 2 with neonatal onset, characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. Neonatal intrahepatic cholestasis due to citrin deficiency is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms. {ECO:0000269|PubMed:11793471}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Metabolism of carbohydrates;Metabolism of proteins;Purine metabolism;Metabolism;Methionine and cysteine metabolism;Vitamin B9 (folate) metabolism;Mitochondrial protein import;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.452

Intolerance Scores

• loftool: 0.637
• rvis_EVS: -1.16
• rvis_percentile_EVS: 6.17

Haploinsufficiency Scores

• pHI: 0.227
• hipred: Y
• hipred_score: 0.557
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc25a13
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system phenotype; 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); hearing/vestibular/ear phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: gluconeogenesis;ATP biosynthetic process;mitochondrial transport;aspartate transmembrane transport;L-glutamate transmembrane transport;malate-aspartate shuttle;cellular respiration;response to calcium ion;L-aspartate transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of plasma membrane
• Molecular function: transporter activity;L-glutamate transmembrane transporter activity;calcium ion binding;acidic amino acid transmembrane transporter activity;L-aspartate transmembrane transporter activity;identical protein binding