SLC5A6

Summary

SLC5A6 (solute carrier family 5 member 6, HGNC:11041) is a protein-coding gene on chromosome 2p23.3, encoding Sodium-dependent multivitamin transporter (Q9Y289). Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide.

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.

Source: NCBI Gene 8884 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration, infantile-onset, biotin-responsive (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 139 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 32
• Druggable target: yes
• MANE Select transcript: NM_021095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11041
Approved symbol	SLC5A6
Name	solute carrier family 5 member 6
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	SMVT
Ensembl gene	ENSG00000138074
Ensembl biotype	protein_coding
OMIM	604024
Entrez	8884

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 36 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000310574, ENST00000401463, ENST00000408041, ENST00000412471, ENST00000414408, ENST00000426119, ENST00000428518, ENST00000430186, ENST00000432106, ENST00000442731, ENST00000445802, ENST00000461319, ENST00000461757, ENST00000464538, ENST00000476319, ENST00000481751, ENST00000488743, ENST00000492069, ENST00000892748, ENST00000892749, ENST00000892750, ENST00000892751, ENST00000892752, ENST00000892753, ENST00000892754, ENST00000892755, ENST00000892756, ENST00000892757, ENST00000926527, ENST00000926528, ENST00000926529, ENST00000926530, ENST00000926531, ENST00000926532, ENST00000926533, ENST00000926534, ENST00000926535, ENST00000926536, ENST00000926537, ENST00000962471, ENST00000962472, ENST00000962473, ENST00000962474, ENST00000962475

RefSeq mRNA: 1 — MANE Select: NM_021095 NM_021095

CCDS: CCDS1740

Canonical transcript exons

ENST00000310574 — 17 exons

Exon	Start	End
ENSE00001035742	27211467	27211533
ENSE00001931648	27212020	27212268
ENSE00003489586	27206877	27206942
ENSE00003541178	27204461	27204590
ENSE00003551295	27203233	27203345
ENSE00003552180	27205350	27205504
ENSE00003556642	27201988	27202074
ENSE00003606440	27206483	27206534
ENSE00003618325	27200998	27201113
ENSE00003635080	27207258	27207790
ENSE00003654809	27201350	27201453
ENSE00003655330	27199587	27200579
ENSE00003656246	27202813	27202880
ENSE00003674403	27201666	27201847
ENSE00003679769	27204791	27204931
ENSE00003689501	27203779	27203867
ENSE00003791572	27206026	27206093

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5392 / max 166.2687, expressed in 1796 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27463	5.1392	1485
27465	4.8647	1700
27464	3.3953	1517
27462	1.5766	663
27461	0.7105	265
27468	0.3925	95
27466	0.1993	49
27467	0.1188	40
27457	0.0635	19
27459	0.0487	23

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.06	gold quality
right testis	UBERON:0004534	95.42	gold quality
left testis	UBERON:0004533	95.32	gold quality
right frontal lobe	UBERON:0002810	93.69	gold quality
testis	UBERON:0000473	93.16	gold quality
placenta	UBERON:0001987	93.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.04	gold quality
body of uterus	UBERON:0009853	92.89	gold quality
endometrium epithelium	UBERON:0004811	92.82	gold quality
left uterine tube	UBERON:0001303	92.59	gold quality
right ovary	UBERON:0002118	92.09	gold quality
omental fat pad	UBERON:0010414	92.08	gold quality
peritoneum	UBERON:0002358	92.04	gold quality
corpus epididymis	UBERON:0004359	91.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.60	gold quality
cerebellar hemisphere	UBERON:0002245	91.36	gold quality
cerebellar cortex	UBERON:0002129	91.15	gold quality
pigmented layer of retina	UBERON:0001782	90.94	gold quality
retina	UBERON:0000966	90.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.64	gold quality
liver	UBERON:0002107	90.57	gold quality
left ovary	UBERON:0002119	90.57	gold quality
gastrocnemius	UBERON:0001388	90.50	gold quality
apex of heart	UBERON:0002098	90.23	gold quality
mucosa of transverse colon	UBERON:0004991	90.13	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.06	gold quality
minor salivary gland	UBERON:0001830	89.82	gold quality
mucosa of stomach	UBERON:0001199	89.68	gold quality
lower esophagus mucosa	UBERON:0035834	89.60	gold quality
muscle of leg	UBERON:0001383	89.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64
E-MTAB-6142	no	132.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF4, TFAP2A

miRNA regulators (miRDB)

42 targeting SLC5A6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3145-5P	98.57	67.83	900

Literature-anchored findings (GeneRIF, showing 25)

• in intestinal and liver epithelial cells, SMVT is the major (if not the only) biotin uptake system that operates. (PMID:12646417)
• biotin uptake by human renal epithelial cells occurs via the hSMVT system and that the process is regulated by intracellular PKC- and Ca(2+)/calmodulin-mediated pathways. (PMID:15561972)
• A sodium-dependent multivitamin transporter, SMVT, responsible for biotin uptake and transport, was identified and functionally characterized in MDCK-MDR1 cells. (PMID:16749865)
• Human intestinal biotin uptake is adaptively regulated but is not mediated via changes in hSMVT RNA stability. (PMID:16959947)
• KLF-4 and AP-2 is regulating the activity of the hSMVT promoter in the intestine and provide direct in vivo confirmation of hSMVT promoter activity. (PMID:17135299)
• findings from this study are consistent with the theory that HCS senses biotin, and that biotin regulates its own cellular uptake by participating in HCS-dependent chromatin remodeling events at the SMVT promoter 1 locus in Jurkat cells. (PMID:17904341)
• Conclude that the COOH tail of hSMVT contains several determinants important for polarized targeting and biotin transport in epithelial cells. (PMID:19211916)
• These results show important role for His(1)(1) and His(2) residues in hSMVT function, which is most probably mediated via an effect on level of hSMVT expression at the cell membrane. (PMID:20962270)
• hSMVT may play an important role in the homeostasis of I(-) in the body (PMID:20980265)
• PDZD11 is an interacting partner with hSMVT in intestinal epithelial cells and that this interaction affects hSMVT function and cell biology. (PMID:21183659)
• Human SMVT protein is glycosylated, and that glycosylation is important for its function. The study also shows a role for the putative PKC-phosphorylation site Thr(286) of hSMVT in the PKC-mediated regulation of biotin uptake. (PMID:21570947)
• Cys(294) is essential for the function of the human sodium-dependent multivitamin transporter. (PMID:22015582)
• PCR analysis had confirmed the existence of FR-alpha, SMVT, and B ((0, +)) in Y-79 and ARPE-19 cells. (PMID:22304562)
• This study for the first time confirms the molecular expression of SMVT and demonstrates that SMVT, responsible for biotin uptake, is functionally active in PC-3 prostate cancer cells (PMID:22732670)
• This study shows for the first time the functional and molecular presence of SMVT in immortalized human corneal epithelial (HCEC) and retinal pigment epithelial (D407) cells (PMID:22927035)
• these studies demonstrated for the first time the functional and molecular expression of sodium dependent multivitamin transporter (SMVT) in human derived breast cancer (T47D) cells (PMID:23142496)
• SLC5A6 is responsible for the supplies of biotin and pantothenic acid into the brain across the blood brain barrier. (PMID:25809983)
• SMVT-mediated transport is highly specific for R-(+)-alpha-lipoic acid. (PMID:25971966)
• S. typhimurium infection inhibits intestinal biotin uptake by SLC5A6, and that the inhibition is mediated via the action of proinflammatory cytokines. (PMID:25999427)
• This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway. (PMID:28052864)
• Integrated profiling identifies SLC5A6 and MFAP2 as novel diagnostic and prognostic biomarkers in gastric cancer patients. (PMID:31894266)
• Novel biallelic variants expand the SLC5A6-related phenotypic spectrum. (PMID:35013551)
• A novel SLC5A6 homozygous variant in a family with multivitamin-dependent neurometabolic disorder: Phenotype expansion and long-term follow-up. (PMID:37391029)
• Novel missense variants cause intermediate phenotypes in the phenotypic spectrum of SLC5A6-related disorders. (PMID:38012394)
• Novel SLC5A6 mutations lead to B lymphocyte maturation defects with metabolic abnormality rescuable by biotin replenishment. (PMID:38036278)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a6b	ENSDARG00000014599
danio_rerio	slc5a6a	ENSDARG00000042859
mus_musculus	Slc5a6	ENSMUSG00000006641
rattus_norvegicus	Slc5a6	ENSRNOG00000057628
drosophila_melanogaster	CG10444	FBGN0034494
drosophila_melanogaster	CG32669	FBGN0052669

Paralogs (12): SLC5A1 (ENSG00000100170), SLC5A4 (ENSG00000100191), SLC5A5 (ENSG00000105641), SLC5A7 (ENSG00000115665), SLC5A9 (ENSG00000117834), SLC5A2 (ENSG00000140675), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), SLC5A8 (ENSG00000256870), (ENSG00000293606)

Protein

Protein identifiers

Sodium-dependent multivitamin transporter — Q9Y289 (reviewed: Q9Y289)

Alternative names: Solute carrier family 5 member 6

All UniProt accessions (10): Q9Y289, E7EMX0, E7ENG0, E7ENN0, E7EP02, E7ERE1, E7EW41, E7EW78, E7EXC0, Q9HD19

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide. Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake. Required for biotin and pantothenate uptake in the intestine across the brush border membrane. Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin. Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier.

Subunit / interactions. Interacts with PDZD11.

Subcellular location. Cell membrane. Apical cell membrane Cell membrane.

Tissue specificity. Expressed in microvessels of the brain (at protein level). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.

Post-translational modifications. May be glycosylated.

Disease relevance. Sodium-dependent multivitamin transporter deficiency (SMVTD) [MIM:618973] An autosomal recessive multisystemic metabolic disorder characterized by early infantile onset, progressive neurodegeneration, global developmental delay, and developmental regression with loss of early motor and cognitive milestones. Additional variable features include seizures, ataxia, spasticity, peripheral neuropathy, immune defects, and osteopenia. Treatment with biotin, pantothenic acid, and lipoate may result in clinical improvement. The disease is caused by variants affecting the gene represented in this entry. Peripheral motor neuropathy, childhood-onset, biotin-responsive (COMNB) [MIM:619903] An autosomal recessive disorder characterized by distal muscle weakness and atrophy appearing late in the first decade of life. The disorder predominantly affects the upper limbs and hands, resulting in difficulties with fine motor skills. Some patients may have lower limb involvement, resulting in gait difficulties. Additional features may include spasticity, ataxia, and cerebellar signs. Sensation is intact, and patients have normal cognitive development. Treatment with biotin, pantothenic acid, and lipoic acid may result in clinical improvement. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal tail is important for biotin uptake as well as apical localization in polarized cells.

Similarity. Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.

RefSeq proteins (1): NP_066918* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001734	Na/solute_symporter	Family
IPR018212	Na/solute_symporter_CS	Conserved_site
IPR038377	Na/Glc_symporter_sf	Homologous_superfamily
IPR051163	Sodium:Solute_Symporter_SSF	Family

Pfam: PF00474

Catalyzed reactions (Rhea), 4 shown:

• iodide(out) + 2 Na(+)(out) = iodide(in) + 2 Na(+)(in) (RHEA:71207)
• (R)-pantothenate(out) + 2 Na(+)(out) = (R)-pantothenate(in) + 2 Na(+)(in) (RHEA:73371)
• biotin(out) + 2 Na(+)(out) = biotin(in) + 2 Na(+)(in) (RHEA:73375)
• (R)-lipoate(out) + 2 Na(+)(out) = (R)-lipoate(in) + 2 Na(+)(in) (RHEA:73379)

UniProt features (59 total): mutagenesis site 35, transmembrane region 13, sequence variant 7, glycosylation site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y289-F1	79.99	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (3): 138, 489, 498

Mutagenesis-validated functional residues (35):

Position	Phenotype
68	no effect on biotin transport.
78	reduced membrane localization. decrease in biotin transport.
104	no effect on biotin transport.
128	no effect on biotin transport.
138	reduced protein levels. decrease in biotin transport.
144	no effect on biotin transport.
187	no effect on biotin transport.
242	no effect on biotin transport.
283	no effect on protein levels or membrane localization.
286	resistant to phorbol 12-myristate 13-acetate (pma)-induced inhibition of biotin transport. no effect on protein levels o
294	reduced membrane localization. decrease in biotin transport (decreased vmax, no change in km).
294	decrease in biotin transport.
309	no effect on biotin transport.
358	no effect on biotin transport.
366	no effect on biotin transport.
410	no effect on biotin transport.
443	no effect on biotin transport.
450	no effect on biotin transport.
489	slight decrease in protein levels. decrease in biotin transport.
498	no effect on biotin transport.
534	no effect on biotin transport.
567–635	loss of biotin transport. loss of membrane localization.
570–635	loss of biotin transport. loss of membrane localization.
575–635	partial loss (75%) of biotine transport. apical membrane localization and intracellular structure localization in polari
577	no effect on biotin transport.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-196780	Biotin transport and metabolism
R-HSA-199220	Vitamin B5 (pantothenate) metabolism
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 293 (showing top): ELVIDGE_HYPOXIA_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, MARTINEZ_RB1_TARGETS_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT

GO Biological Process (11): biotin metabolic process (GO:0006768), sodium ion transport (GO:0006814), biotin transport (GO:0015878), pantothenate transmembrane transport (GO:0015887), transport across blood-brain barrier (GO:0150104), iodide transmembrane transport (GO:1904200), biotin import across plasma membrane (GO:1905135), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085), obsolete inorganic ion transmembrane transport (GO:0098660), sodium ion import across plasma membrane (GO:0098719)

GO Molecular Function (13): sodium-dependent multivitamin transmembrane transporter activity (GO:0008523), iodide transmembrane transporter activity (GO:0015111), biotin transmembrane transporter activity (GO:0015225), pantothenate transmembrane transporter activity (GO:0015233), pantothenate:sodium symporter activity (GO:0015498), vitamin transmembrane transporter activity (GO:0090482), monocarboxylate:sodium symporter activity (GO:0140161), protein binding (GO:0005515), monoatomic ion transmembrane transporter activity (GO:0015075), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), obsolete amide transmembrane transporter activity (GO:0042887), sulfur compound transmembrane transporter activity (GO:1901682)

GO Cellular Component (6): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	2
SLC-mediated transmembrane transport	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vitamin transmembrane transport	3
vitamin transmembrane transporter activity	3
monocarboxylic acid transmembrane transporter activity	3
transmembrane transporter activity	3
plasma membrane region	3
monocarboxylic acid transport	2
carboxylic acid transmembrane transport	2
iodide transport	2
biotin transport	2
transport	2
modified amino acid transmembrane transporter activity	2
sulfur compound metabolic process	1
monocarboxylic acid metabolic process	1
metal ion transport	1
vitamin transport	1
nitrogen compound transport	1
sulfur compound transport	1
modified amino acid transport	1
vascular transport	1
monoatomic anion transmembrane transport	1
import across plasma membrane	1
cellular process	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
solute:sodium symporter activity	1
monoatomic anion transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
pantothenate transmembrane transport	1
sodium ion import across plasma membrane	1
monocarboxylate:sodium symporter activity	1
organic acid:sodium symporter activity	1
binding	1
monoatomic ion transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
basal part of cell	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1163 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A6	SLC22A12	Q96S37	629
SLC5A6	HLCS	P50747	625
SLC5A6	PDZD11	Q5EBL8	609
SLC5A6	SLC5A7	Q9GZV3	581
SLC5A6	SLC26A4	O43511	574
SLC5A6	BTD	P43251	552
SLC5A6	SLC19A2	O60779	459
SLC5A6	SLC23A1	Q9UHI7	454
SLC5A6	SLC19A3	Q9BZV2	438
SLC5A6	SLC16A5	O15375	420
SLC5A6	SLC15A1	P46059	416
SLC5A6	SLC23A2	Q9UGH3	414
SLC5A6	SLC16A1	P53985	406
SLC5A6	PC	P11498	397
SLC5A6	SLC16A9	Q7RTY1	396

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDZD11	SLC5A6	psi-mi:“MI:0915”(physical association)	0.600
SLC5A6	PDZD11	psi-mi:“MI:0915”(physical association)	0.600
PDZD11	SLC5A6	psi-mi:“MI:0403”(colocalization)	0.600
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC5A6	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
GALNT6	SLC5A6	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PDZK1P1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
CMTM8	UBXN8	psi-mi:“MI:0914”(association)	0.350
GPR12	TLCD2	psi-mi:“MI:0914”(association)	0.350
PDZK1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
SLC5A6	SLC31A1	psi-mi:“MI:0914”(association)	0.350
MBLAC2	CD63	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
LRRC25	SCAMP3	psi-mi:“MI:0914”(association)	0.350
FPR2	SCAMP3	psi-mi:“MI:0914”(association)	0.350
BSND	PLD2	psi-mi:“MI:0914”(association)	0.350
HLA-B	RAB29	psi-mi:“MI:0914”(association)	0.350
P2RY8	BTAF1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC5A6	TTC33	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): SLC5A6 (Proximity Label-MS), SLC5A6 (Affinity Capture-MS), SLC5A6 (Reconstituted Complex), SLC5A6 (Affinity Capture-RNA), SLC5A6 (Affinity Capture-MS), SLC5A6 (Affinity Capture-MS), SLC5A6 (Affinity Capture-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Proximity Label-MS), SLC5A6 (Affinity Capture-MS), SLC5A6 (Two-hybrid)

ESM2 similar proteins: A0A075B734, A1L272, A2VDL4, A9Y006, O14520, O35454, O35874, O54794, O70247, P34080, P47862, P49281, P51797, P56402, P56403, P57057, P63115, P63116, Q04671, Q08C93, Q08DE6, Q2YDU8, Q4R691, Q571F8, Q5R839, Q5U4D8, Q62052, Q8BJA2, Q8CFY5, Q8CIZ9, Q8IVJ1, Q8K078, Q8MIQ9, Q8NA29, Q8R070, Q8R139, Q8R2N1, Q92482, Q96BD0, Q96GZ6

Diamond homologs: A7MBD8, O70247, P83740, Q1EHB4, Q3ZMH1, Q49B93, Q5BL81, Q5U4D8, Q63008, Q7SYH5, Q7T384, Q8BYF6, Q8N695, Q92911, Q99PN0, Q9XT77, Q9Y289, Q5E733

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

139 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	70
Likely benign	29
Benign	7

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1341576	NM_021095.4(SLC5A6):c.1005+1G>A	Pathogenic
2064630	NM_021095.4(SLC5A6):c.424C>T (p.Arg142Ter)	Pathogenic
2073503	NM_021095.4(SLC5A6):c.829C>T (p.Gln277Ter)	Pathogenic
975022	NM_021095.4(SLC5A6):c.1199G>C (p.Arg400Thr)	Pathogenic
975023	NM_021095.4(SLC5A6):c.280C>T (p.Arg94Ter)	Pathogenic
975024	NM_021095.4(SLC5A6):c.368G>T (p.Arg123Leu)	Pathogenic
1341577	NM_021095.4(SLC5A6):c.1865_1866del (p.Gln622fs)	Likely pathogenic
2507024	NM_021095.4(SLC5A6):c.460-19T>G	Likely pathogenic
2627917	NM_021095.4(SLC5A6):c.1403del (p.Phe468fs)	Likely pathogenic
4291821	NM_021095.4(SLC5A6):c.1648+2T>G	Likely pathogenic
4845873	NM_021095.4(SLC5A6):c.957C>G (p.Tyr319Ter)	Likely pathogenic

SpliceAI

3550 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27200577:GTCC:G	acceptor_loss	1.0000
2:27201661:CTTAC:C	donor_loss	1.0000
2:27201662:TTACT:T	donor_loss	1.0000
2:27201663:TACTT:T	donor_loss	1.0000
2:27201664:A:AC	donor_gain	1.0000
2:27201664:AC:A	donor_loss	1.0000
2:27201665:C:CG	donor_loss	1.0000
2:27201665:C:CT	donor_gain	1.0000
2:27201844:CACC:C	acceptor_gain	1.0000
2:27201846:CC:C	acceptor_gain	1.0000
2:27201847:CC:C	acceptor_gain	1.0000
2:27201849:T:A	acceptor_loss	1.0000
2:27201948:T:TA	donor_gain	1.0000
2:27203774:GGTA:G	donor_loss	1.0000
2:27203775:GTAC:G	donor_loss	1.0000
2:27203776:TACCT:T	donor_loss	1.0000
2:27203777:A:AG	donor_loss	1.0000
2:27203778:C:A	donor_loss	1.0000
2:27203864:CGAA:C	acceptor_gain	1.0000
2:27203868:C:CC	acceptor_gain	1.0000
2:27203869:T:A	acceptor_loss	1.0000
2:27204455:TCTCA:T	donor_loss	1.0000
2:27204456:CTCA:C	donor_loss	1.0000
2:27204457:TCA:T	donor_loss	1.0000
2:27204458:CA:C	donor_loss	1.0000
2:27204459:A:AT	donor_loss	1.0000
2:27204460:C:G	donor_loss	1.0000
2:27204779:C:A	donor_gain	1.0000
2:27204786:CTCA:C	donor_loss	1.0000
2:27204787:TCA:T	donor_loss	1.0000

AlphaMissense

4075 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27206925:G:C	F137L	0.999
2:27206925:G:T	F137L	0.999
2:27206927:A:G	F137L	0.999
2:27203345:G:C	S365R	0.998
2:27203345:G:T	S365R	0.998
2:27203780:T:G	S365R	0.998
2:27206522:C:G	G158R	0.998
2:27206522:C:T	G158R	0.998
2:27206926:A:G	F137S	0.998
2:27207267:A:C	S128R	0.998
2:27207267:A:T	S128R	0.998
2:27207269:T:G	S128R	0.998
2:27201823:C:A	G463W	0.997
2:27203790:G:C	S361R	0.997
2:27203790:G:T	S361R	0.997
2:27203792:T:G	S361R	0.997
2:27204817:A:C	S283R	0.997
2:27204817:A:T	S283R	0.997
2:27204819:T:G	S283R	0.997
2:27204851:C:T	G272E	0.997
2:27206889:G:C	F149L	0.997
2:27206889:G:T	F149L	0.997
2:27206891:A:G	F149L	0.997
2:27206942:A:G	Y132H	0.997
2:27202031:C:T	G440E	0.996
2:27202032:C:G	G440R	0.996
2:27202032:C:T	G440R	0.996
2:27202868:C:T	G407E	0.996
2:27204797:G:T	A290D	0.996
2:27204844:G:C	N274K	0.996

dbSNP variants (sampled 300 via entrez): RS1000109313 (2:27211259 C>G), RS1000137796 (2:27203568 A>C), RS1000701977 (2:27203463 C>G,T), RS1001218868 (2:27203720 C>A,T), RS1001319698 (2:27204699 T>A), RS1001449501 (2:27213931 C>A,G), RS1001603838 (2:27204371 A>G,T), RS1001680093 (2:27208330 G>A), RS1001781069 (2:27202086 G>C), RS1001811975 (2:27202426 T>C), RS1001834084 (2:27212611 C>T), RS1001935191 (2:27214548 T>G), RS1002046414 (2:27207297 G>A), RS1002085358 (2:27209406 A>G), RS1002085360 (2:27200691 G>A,C)

Disease associations

OMIM: gene MIM:604024 | disease phenotypes: MIM:619903, MIM:618973

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration, infantile-onset, biotin-responsive	Strong	Autosomal recessive
peripheral motor neuropathy, childhood-onset, biotin-responsive	Strong	Autosomal recessive
inherited neurodegenerative disorder	Moderate	Autosomal recessive

Mondo (3): peripheral motor neuropathy, childhood-onset, biotin-responsive (MONDO:0859255), neurodegeneration, infantile-onset, biotin-responsive (MONDO:0033546), inherited neurodegenerative disorder (MONDO:0024237)

Orphanet (1): Sodium-dependent multivitamin transporter deficiency (Orphanet:521268)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000252	Microcephaly
HP:0000639	Nystagmus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001644	Dilated cardiomyopathy
HP:0002059	Cerebral atrophy
HP:0002075	Dysdiadochokinesis
HP:0002079	Hypoplasia of the corpus callosum
HP:0002126	Polymicrogyria
HP:0002216	Premature graying of hair
HP:0002280	Enlarged cisterna magna
HP:0002421	Poor head control
HP:0002522	Areflexia of lower limbs
HP:0002572	Episodic vomiting
HP:0003393	Thenar muscle atrophy
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004315	Decreased circulating IgG concentration
HP:0007181	Interosseus muscle atrophy
HP:0009053	Distal lower limb muscle weakness
HP:0009830	Peripheral neuropathy
HP:0011471	Gastrostomy tube feeding in infancy
HP:0012110	Hypoplasia of the pons
HP:0033685	Fiber type grouping

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007858_4	Fasting blood glucose adjusted for BMI	1.000000e-07
GCST012020_244	Serum metabolite levels	4.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020271	Heredodegenerative Disorders, Nervous System	C10.574.500; C16.320.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066511 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.27	Kd	533.7	nM	CHEMBL5653589
6.27	ED50	533.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149431: Binding affinity to human SLC5A6 incubated for 45 mins by Kinobead based pull down assay	kd	0.5337	uM

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Biotin	increases transport, affects expression, increases uptake, affects reaction, increases reaction (+1 more)	3
bisphenol A	affects expression, decreases expression	2
Estradiol	increases expression	2
Sodium	affects reaction, increases transport, increases reaction	2
Valproic Acid	increases methylation, affects expression	2
Cadmium Chloride	decreases expression	2
FR900359	affects phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
dicrotophos	increases expression	1
chelerythrine	decreases reaction, increases transport	1
mono-(2-ethylhexyl)phthalate	decreases reaction, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
calmidazolium	decreases reaction, increases transport	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-phenylbutyric acid	increases expression, decreases reaction	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Azides	decreases reaction, increases transport	1
Benzo(a)pyrene	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652473	Binding	Binding affinity to human SLC5A6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3HJ	Abcam HEK293T SLC5A6 KO	Transformed cell line	Female
CVCL_D4Q4	HCT116-SLC5A6-KO-c3	Cancer cell line	Male
CVCL_D4Q5	HCT116-SLC5A6-KO-c5	Cancer cell line	Male
CVCL_TP00	HAP1 SLC5A6 (-) 1	Cancer cell line	Male
CVCL_TP01	HAP1 SLC5A6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01498263	Not specified	COMPLETED	Inherited Diseases, Caregiving, and Social Networks