SLC13A5

solute carrier family 13 member 5, the group of Solute carrier family 13

Basic information

Region (hg38): 17:6684718-6713377

Links

ENSG00000141485 ∙ NCBI:284111 ∙ OMIM:608305 ∙ HGNC:23089 ∙ Uniprot:Q86YT5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyridoxine-dependent epilepsy (Supportive), mode of inheritance: AR
• amelocerebrohypohidrotic syndrome (Supportive), mode of inheritance: AR
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 25 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 25, with ameliogenesis imperfecta	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Neurologic	24995870; 26384929; 27600704; 27913086
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC13A5 gene.

• Developmental and epileptic encephalopathy, 25 (558 variants)
• not provided (174 variants)
• Inborn genetic diseases (71 variants)
• not specified (46 variants)
• Undetermined early-onset epileptic encephalopathy (1 variants)
• SLC13A5-related condition (1 variants)
• Microcephaly (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC13A5 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	156	2	161
missense		9	243			252
nonsense	5	2	1			8
start loss			1			1
frameshift	9	1	1			11
inframe indel			8			8
splice donor/acceptor (+/-2bp)	1	9	1			11
splice region			10	25		35
non coding			3	104	54	161
Total	15	21	261	260	56

Highest pathogenic variant AF is 0.0000197

Variants in SLC13A5

This is a list of pathogenic ClinVar variants found in the SLC13A5 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-6685892-C-T			Benign (Jun 28, 2018)
17-6686031-A-T			Benign (Jun 14, 2018)
17-6686176-A-G			Benign (Jun 25, 2018)
17-6686209-A-G		Developmental and epileptic encephalopathy, 25	Uncertain significance (Aug 31, 2022)
17-6686213-C-G			Uncertain significance (Mar 06, 2017)
17-6686216-AAT-A		Developmental and epileptic encephalopathy, 25	Uncertain significance (Mar 17, 2023)
17-6686223-G-A		Developmental and epileptic encephalopathy, 25	Uncertain significance (May 07, 2022)
17-6686225-C-T		Developmental and epileptic encephalopathy, 25	Likely benign (Oct 16, 2023)
17-6686227-C-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Dec 04, 2020)
17-6686228-A-G			Likely benign (Jun 01, 2022)
17-6686241-G-A		Developmental and epileptic encephalopathy, 25	Uncertain significance (Aug 09, 2022)
17-6686260-A-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Jun 15, 2023)
17-6686268-C-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Apr 18, 2023)
17-6686269-G-A		Developmental and epileptic encephalopathy, 25	Uncertain significance (Aug 16, 2022)
17-6686271-C-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Jul 26, 2022)
17-6686279-G-C			Uncertain significance (Sep 14, 2022)
17-6686282-G-A		Developmental and epileptic encephalopathy, 25	Likely benign (Aug 31, 2022)
17-6686285-A-G		not specified • Developmental and epileptic encephalopathy, 25	Likely benign (Dec 06, 2023)
17-6686286-G-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Jul 01, 2022)
17-6686287-C-A			Uncertain significance (May 09, 2019)
17-6686290-A-G		Developmental and epileptic encephalopathy, 25	Likely benign (Feb 25, 2023)
17-6686292-A-C		Developmental and epileptic encephalopathy, 25	Uncertain significance (Mar 13, 2022)
17-6686292-A-G		Developmental and epileptic encephalopathy, 25	Uncertain significance (Feb 09, 2022)
17-6686299-A-G		Developmental and epileptic encephalopathy, 25	Uncertain significance (Aug 24, 2023)
17-6686308-C-T		Developmental and epileptic encephalopathy, 25	Uncertain significance (Jul 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC13A5	protein_coding	protein_coding	ENST00000433363	12	28855

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000506	0.998	125722	0	25	125747	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	288	348	0.828	0.0000202	3702
Missense in Polyphen		81	114.27	0.70884		1209
Synonymous	-0.155	153	151	1.02	0.00000989	1171
Loss of Function	2.83	10	25.4	0.394	0.00000117	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: High-affinity sodium/citrate cotransporter that mediates citrate entry into cells. The transport process is electrogenic; it is the trivalent form of citrate rather than the divalent form that is recognized as a substrate. May facilitate the utilization of circulating citrate for the generation of metabolic energy and for the synthesis of fatty acids and cholesterol. {ECO:0000269|PubMed:12445824, ECO:0000269|PubMed:26384929}.
• Pathway: Bile salt and organic anion SLC transporters;Sodium-coupled sulphate, di- and tri-carboxylate transporters;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;TCA cycle (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.613
• rvis_EVS: -1.4
• rvis_percentile_EVS: 4.19

Haploinsufficiency Scores

• pHI: 0.0907
• hipred: Y
• hipred_score: 0.620
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.429

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc13a5
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype

Gene ontology

• Biological process: sodium ion transport;citrate transport;tricarboxylic acid transmembrane transport;succinate transmembrane transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: citrate transmembrane transporter activity;succinate transmembrane transporter activity;sodium:dicarboxylate symporter activity