SLC5A6

solute carrier family 5 member 6, the group of Solute carrier family 5

Basic information

Region (hg38): 2:27199586-27212958

Links

ENSG00000138074 ∙ NCBI:8884 ∙ OMIM:604024 ∙ HGNC:11041 ∙ Uniprot:Q9Y289 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration, infantile-onset, biotin-responsive (Strong), mode of inheritance: AR
• inherited neurodegenerative disorder (Moderate), mode of inheritance: AR
• neurodegeneration, infantile-onset, biotin-responsive (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, infantile-onset, biotin-responsive; Sodium-dependent multivitamin transporter deficiency	AR	Biochemical	Individuals with Neurodegeneration, infantile-onset, biotin-responsive may respond to biotin, as well as other medical treatments; Sodium-dependent multivitamin transporter deficiency is a multisystem metabolic disorder, and medical/dietary treatment (with biotin, pantothenic acid, and alpha-lipoic acid) has been shown to result in clinical improvement	Biochemical; Neurologic	27904971; 31392107; 31754459; 35013551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC5A6 gene.

• Inborn genetic diseases (27 variants)
• not provided (22 variants)
• Neurodegeneration, infantile-onset, biotin-responsive (10 variants)
• Peripheral motor neuropathy, childhood-onset, biotin-responsive (4 variants)
• SLC5A6-related disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC5A6 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	4	7
missense		1	25	10	2	38
nonsense	3					3
start loss						0
frameshift		3				3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region						0
non coding		1				1
Total	4	6	25	13	6

Highest pathogenic variant AF is 0.0000986

Variants in SLC5A6

This is a list of pathogenic ClinVar variants found in the SLC5A6 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-27200457-G-C		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
2-27200464-G-T		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
2-27200477-CCT-C		Neurodegeneration, infantile-onset, biotin-responsive • Peripheral motor neuropathy, childhood-onset, biotin-responsive	Likely pathogenic (Feb 08, 2023)
2-27201024-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
2-27201040-C-T			Benign (Dec 26, 2018)
2-27201042-G-A		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
2-27201088-G-T		Inborn genetic diseases	Uncertain significance (Aug 23, 2021)
2-27201104-C-T		Neurodegeneration, infantile-onset, biotin-responsive	Likely benign (Aug 12, 2021)
2-27201355-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
2-27201359-G-C		Inborn genetic diseases	Likely benign (Dec 28, 2022)
2-27201380-C-A		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
2-27201669-G-A		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
2-27201709-C-T		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
2-27201735-C-T			Benign (Dec 26, 2018)
2-27201750-G-A		Inborn genetic diseases	Likely benign (Jan 04, 2022)
2-27201755-G-C			Likely benign (Jun 13, 2018)
2-27201768-G-A			Benign (Jul 02, 2020)
2-27201771-C-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2022)
2-27201778-T-G		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
2-27201784-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
2-27201785-G-A			Benign (Apr 05, 2018)
2-27201796-T-C		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
2-27201796-T-G		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
2-27201806-GA-G		Neurodegeneration, infantile-onset, biotin-responsive	Likely pathogenic (Aug 02, 2023)
2-27201817-C-A		Inborn genetic diseases	Likely benign (Dec 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC5A6	protein_coding	protein_coding	ENST00000310574	15	13372

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00608	0.994	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.63	291	380	0.765	0.0000219	4060
Missense in Polyphen		72	135.16	0.53271		1405
Synonymous	0.207	155	158	0.979	0.00000940	1385
Loss of Function	3.61	10	32.0	0.312	0.00000175	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000296	0.000296
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000246	0.000246
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transports pantothenate, biotin and lipoate in the presence of sodium.
• Pathway: Vitamin digestion and absorption - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Biotin transport and metabolism;Vitamin B5 - CoA biosynthesis from pantothenate;Metabolism;Vitamin B5 (pantothenate) metabolism;Transport of vitamins, nucleosides, and related molecules;SLC-mediated transmembrane transport;Transport of small molecules;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Lipoate metabolism;Vitamin H (biotin) metabolism (Consensus)

Intolerance Scores

• loftool: 0.125
• rvis_EVS: -0.09
• rvis_percentile_EVS: 47.06

Haploinsufficiency Scores

• pHI: 0.280
• hipred: N
• hipred_score: 0.476
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.504

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc5a6
• 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); digestive/alimentary phenotype; limbs/digits/tail phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: sodium ion transport;biotin transport;pantothenate transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;vesicle membrane;membrane;brush border membrane
• Molecular function: sodium-dependent multivitamin transmembrane transporter activity