SLC12A5

solute carrier family 12 member 5, the group of Solute carrier family 12

Basic information

Region (hg38): 20:46021690-46060150

Links

ENSG00000124140

∙ NCBI:57468 ∙ OMIM:606726 ∙ HGNC:13818 ∙ Uniprot:Q9H2X9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
developmental and epileptic encephalopathy, 34 (Strong), mode of inheritance: AR
developmental and epileptic encephalopathy, 34 (Moderate), mode of inheritance: AR
epilepsy, idiopathic generalized, susceptibility to, 14 (No Known Disease Relationship), mode of inheritance: AD
epilepsy, idiopathic generalized, susceptibility to, 14 (Limited), mode of inheritance: AD
developmental and epileptic encephalopathy, 34 (Limited), mode of inheritance: AR
genetic developmental and epileptic encephalopathy (Limited), mode of inheritance: AR
epilepsy of infancy with migrating focal seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 34	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	Neurologic	26333769

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A5 gene.

Developmental_and_epileptic_encephalopathy,_34 (855 variants)
not_specified (94 variants)
not_provided (70 variants)
Epilepsy,_idiopathic_generalized,_susceptibility_to,_14 (23 variants)
SLC12A5-related_disorder (17 variants)
See_cases (2 variants)
Developmental_and_epileptic_encephalopathy (1 variants)
Microcephaly (1 variants)
Intellectual_disability (1 variants)
Movement_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020708.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	290 clinvar	5 clinvar	302
missense	1 clinvar	5 clinvar	337 clinvar	9 clinvar		352
nonsense	11 clinvar	2 clinvar	1 clinvar			14
start loss						0
frameshift	16 clinvar					16
splice donor/acceptor (+/-2bp)		7 clinvar	2 clinvar	1 clinvar		10
Total	28	14	347	300	5

Highest pathogenic variant AF is 0.00000186084

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC12A5	protein_coding	protein_coding	ENST00000454036	26	38429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.81e-7	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.70	347	696	0.498	0.0000404	7435
Missense in Polyphen		63	256.45	0.24566		2697
Synonymous	1.01	253	274	0.922	0.0000161	2301
Loss of Function	6.58	3	56.3	0.0533	0.00000295	621

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000183	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis. As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262). {ECO:0000250|UniProtKB:Q63633, ECO:0000269|PubMed:24668262}.;
Disease: DISEASE: Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685]: An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. {ECO:0000269|PubMed:24668262, ECO:0000269|PubMed:24928908, ECO:0000269|PubMed:26528127}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway: GABAergic synapse - Homo sapiens (human);Cation-coupled Chloride cotransporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

pRec: 0.153

Intolerance Scores

loftool: 0.00861
rvis_EVS: -1.37
rvis_percentile_EVS: 4.45

Haploinsufficiency Scores

pHI: 0.613
hipred: Y
hipred_score: 0.809
ghis: 0.628

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.366

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc12a5
Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hearing/vestibular/ear 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);

Zebrafish Information Network

Gene name: slc12a5b
Affected structure: retinal ganglion cell
Phenotype tag: abnormal
Phenotype quality: decreased functionality

Gene ontology

Biological process: ion transport;cellular ion homeostasis;cell volume homeostasis;hypotonic response;chemical synaptic transmission;learning;cellular chloride ion homeostasis;multicellular organism growth;thermosensory behavior;response to drug;chloride ion homeostasis;potassium ion homeostasis;dendritic spine development;chloride transmembrane transport;potassium ion import across plasma membrane
Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane
Molecular function: chloride transmembrane transporter activity;potassium:chloride symporter activity