SLC12A6

solute carrier family 12 member 6, the group of Solute carrier family 12

Basic information

Region (hg38): 15:34229784-34338060

Previous symbols: [ "KCC3", "ACCPN" ]

Links

ENSG00000140199 ∙ NCBI:9990 ∙ OMIM:604878 ∙ HGNC:10914 ∙ Uniprot:Q9UHW9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• agenesis of the corpus callosum with peripheral neuropathy (Supportive), mode of inheritance: AR
• agenesis of the corpus callosum with peripheral neuropathy (Limited), mode of inheritance: AD
• agenesis of the corpus callosum with peripheral neuropathy (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease, axonal, IIa 2II (Strong), mode of inheritance: AD
• agenesis of the corpus callosum with peripheral neuropathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, axonal, type 2II; Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome)	AD/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	Craniofacial; Musculoskeletal; Neurologic	14397896; 6329500; 12368912; 12838516; 16606917; 17893295; 20020398; 20301546; 27485015; 31439721; 33323309; 34706912; 35733399

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC12A6 gene.

• not_provided (1284 variants)
• Agenesis_of_the_corpus_callosum_with_peripheral_neuropathy (351 variants)
• Inborn_genetic_diseases (141 variants)
• not_specified (49 variants)
• Charcot-Marie-Tooth_disease,_axonal,_IIa_2II (32 variants)
• SLC12A6-related_disorder (24 variants)
• Charcot-Marie-Tooth_disease (9 variants)
• Peripheral_neuropathy (2 variants)
• Corpus_callosum,_agenesis_of (1 variants)
• See_cases (1 variants)
• Autosomal_recessive_axonal_hereditary_motor_and_sensory_neuropathy (1 variants)
• Abnormal_facial_shape (1 variants)
• Low-set_ears (1 variants)
• Clinodactyly_of_the_5th_finger (1 variants)
• Hypertelorism (1 variants)
• Usher_syndrome_type_1C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC12A6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001365088.1. 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	29	452	6	488
missense	5	14	423	11	1	454
nonsense	27	30				57
start loss			3			3
frameshift	28	78	2			108
splice donor/acceptor (+/-2bp)	3	44	2			49
Total	63	167	459	463	7

Highest pathogenic variant AF is 0.0000285142

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC12A6	protein_coding	protein_coding	ENST00000354181	25	104802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0114	0.989	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.96	436	648	0.673	0.0000374	7527
Missense in Polyphen		157	327.53	0.47935		3835
Synonymous	0.0760	228	229	0.994	0.0000129	2293
Loss of Function	5.49	17	64.6	0.263	0.00000415	687

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000789	0.000788
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.
• Disease: DISEASE: Agenesis of the corpus callosum, with peripheral neuropathy (ACCPN) [MIM:218000]: A disease that is characterized by severe progressive sensorimotor neuropathy, mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;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: 0.262

Intolerance Scores

• loftool: 0.0254
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.51

Haploinsufficiency Scores

• pHI: 0.381
• hipred: Y
• hipred_score: 0.512
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.393

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc12a6
• 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; cellular phenotype; muscle phenotype; vision/eye phenotype; reproductive system phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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

Gene ontology

• Biological process: angiogenesis;ion transport;cell volume homeostasis;chemical synaptic transmission;chloride ion homeostasis;potassium ion homeostasis;cellular hypotonic salinity response;chloride transmembrane transport;potassium ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;basolateral plasma membrane
• Molecular function: potassium:chloride symporter activity