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): 7:96120220-96322147

Previous symbols: [ "CTLN2" ]

Links

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

Phenotypes

GenCC

Source: genCC

• citrin deficiency (Definitive), mode of inheritance: AR
• citrullinemia, type II, adult-onset (Strong), mode of inheritance: AR
• citrullinemia type II (Supportive), mode of inheritance: AR
• neonatal intrahepatic cholestasis due to citrin deficiency (Supportive), mode of inheritance: AR
• neonatal intrahepatic cholestasis due to citrin deficiency (Strong), mode of inheritance: AR
• citrullinemia, type II, adult-onset (Strong), 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 (676 variants)
• not_provided (132 variants)
• Citrullinemia,_type_II,_adult-onset (127 variants)
• Neonatal_intrahepatic_cholestasis_due_to_citrin_deficiency (82 variants)
• Inborn_genetic_diseases (77 variants)
• Citrullinemia (77 variants)
• SLC25A13-related_disorder (63 variants)
• Citrullinemia_type_II (61 variants)
• not_specified (35 variants)
• Adult-onset_citrullinemia_type_I (21 variants)
• Citrullinemia_type_I (21 variants)
• CITRIN_DEFICIENCY,_NEONATAL_ONSET (3 variants)
• Short-rib_thoracic_dysplasia_6_with_or_without_polydactyly (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. These statistics are base on transcript: NM_000014251.3. 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		1	8	246	4	259
missense	6	24	193	6		229
nonsense	28	22				50
start loss		1	2			3
frameshift	39	37	4			80
splice donor/acceptor (+/-2bp)	16	33	2			51
Total	89	118	209	252	4

Highest pathogenic variant AF is 0.0001146124

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
		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

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

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