SLC5A6

protein-coding

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

Gene summary

Enables biotin transmembrane transporter activity; iodide transmembrane transporter activity; and pantothenate transmembrane transporter activity. Involved in iodide transmembrane transport; transport across blood-brain barrier; and vitamin transmembrane transport. Located in apical plasma membrane. Implicated in vitamin metabolic disorder. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021095.4

Inheritance

ClinVar variants

P:16U:77B:45

Top phenotype

Neurodegeneration, infantile-onset, biotin-responsive; Sodium-dependent multivitamin transporter deficiency

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr2:27,199,587-27,212,958

External References & Databases

Ensembl (ENSG00000138074)

Transcript & Mutation Effects

hg38 • Region Span ~13.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited neurodegenerative disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0024237

Submitter: Illumina

neurodegeneration, infantile-onset, biotin-responsiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033546

Submitter: Ambry Genetics

neurodegeneration, infantile-onset, biotin-responsiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033546

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration, infantile-onset, biotin-responsiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033546

Submitter: G2P

neurodegeneration, infantile-onset, biotin-responsiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033546

Submitter: PanelApp Australia

peripheral motor neuropathy, childhood-onset, biotin-responsiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859255

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodegeneration, infantile-onset, biotin-responsive; Sodium-dependent multivitamin transporter deficiencyAR

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: 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

Refs: 27904971; 31392107; 31754459; 35013551

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC5A6 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 78

not providedTotal: 38

Neurodegeneration, infantile-onset, biotin-responsiveTotal: 19

SLC5A6-related disorderTotal: 11

Peripheral motor neuropathy, childhood-onset, biotin-responsiveTotal: 7

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021095.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	15 clinvar	5 clinvar	22
missense	2 clinvar	3 clinvar	71 clinvar	24 clinvar	1 clinvar	101
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss						0
frameshift		3 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	3 clinvar			6
Total	6	10	77	39	6	138

Highest pathogenic variant AF is 0.00017849109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 81 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021095.4	RefSeq	NP_066918.2	15	MANE Select
ENST00000310574.8	Ensembl	ENSP00000310208.3	15	MANE Select
ENST00000401463.5	Ensembl	ENSP00000384265.1	2	Standard
ENST00000408041.5	Ensembl	ENSP00000384853.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vitamin digestion and absorption - Homo sapiens (human)
Nuclear Receptors Meta-Pathway
NRF2 pathway
Biotin transport and metabolism
Vitamin B5 - CoA biosynthesis from pantothenate

Biological Process

sodium ion transport
biotin transport
pantothenate transmembrane transport

Molecular Function

sodium-dependent multivitamin transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
vesicle membrane
membrane
brush border membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310574
Coding exons: 15
Length: 13372
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	291	380	0.765	0.0000219	4060
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transports pantothenate, biotin and lipoate in the presence of sodium.;

Intolerance Scores

LoFtool: 0.125
RVIS EVS: -0.09
RVIS percentile EVS: 47.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.504

Gene Damage Prediction

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