GeneBe

SLC13A5

protein-coding

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

Gene summary

This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

MANE transcript

NM_177550.5

Inheritance

AR, AD

ClinVar variants

P:66U:282B:218

Top phenotype

Developmental and epileptic encephalopathy 25, with ameliogenesis imperfecta

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr17:6,684,719-6,713,377

External References & Databases

Ensembl (ENSG00000141485)NCBI Gene (284111)OMIM (608305)HGNC:23089GenCCUniProt (Q86YT5)AlphaFoldClinVar (SLC13A5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~28.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 25STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014392

Submitter: PanelApp Australia

developmental and epileptic encephalopathy, 25STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014392

Submitter: Labcorp Genetics (formerly Invitae)

amelocerebrohypohidrotic syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009185

Submitter: Orphanet

developmental and epileptic encephalopathy, 25DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014392

Submitter: G2P

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 25, with ameliogenesis imperfectaAR

Manifestation: Dental; Neurologic

Intervention: General

Rationale: 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

Comments: As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

Refs: 24995870; 26384929; 27600704; 27913086Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC13A5 variants in ClinVar

13 Conditions Cataloged
Developmental and epileptic encephalopathy, 25Total: 652
not providedTotal: 171
Inborn genetic diseasesTotal: 108
not specifiedTotal: 77
SLC13A5-related disorderTotal: 24
Epileptic encephalopathyTotal: 2
Undetermined early-onset epileptic encephalopathyTotal: 1
Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177550.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
205
clinvar
 207
missense
1
clinvar
13
clinvar
275
clinvar
13
clinvar
 302
nonsense
7
clinvar
4
clinvar
2
clinvar
 13
start loss
1
clinvar
 1
frameshift
16
clinvar
7
clinvar
2
clinvar
 25
splice donor/acceptor (+/-2bp)
3
clinvar
15
clinvar
 18
Total27392822180566

Highest pathogenic variant AF is 0.00018028713

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_177550.5RefSeqNP_808218.112MANE Select
ENST00000433363.7EnsemblENSP00000406220.212MANE Select
NM_001143838.3RefSeqNP_001137310.111Standard
NM_001284509.2RefSeqNP_001271438.112Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • sodium ion transport
  • citrate transport
  • tricarboxylic acid transmembrane transport
  • succinate transmembrane transport

Molecular Function

  • citrate transmembrane transporter activity
  • succinate transmembrane transporter activity
  • sodium:dicarboxylate symporter activity

Cellular Component

  • plasma membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000433363
Coding exons
12
Length
28855
Individuals with no LoFs
125722
Homozygous LoFs
0
Heterozygous LoFs
25
Defined
125747
p
0.0000994
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.142883480.8280.00002023702
Missense (PolyPhen)81114.270.708841209
Synonymous-0.1551531511.020.000009891171
Loss of Function2.831025.40.3940.00000117283

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000120.00012rare
South Asian0.000160.00016rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.121

Intolerance Scores

LoFtool
0.613
RVIS EVS
-1.4
RVIS percentile EVS
4.19

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.429

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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