SLC5A6

Chr 2AR

solute carrier family 5 member 6

Also known as: COMNB, NERIB, SMVT, SMVTD, hSMVT

NCBI Gene: 8884ENSG00000138074UniProt: Q9Y289

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. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Peripheral motor neuropathy, childhood-onset, biotin-responsiveMIM #619903
AR
Sodium-dependent multivitamin transporter deficiencyMIM #618973
AR
0
Active trials
28
Pathogenic / LP
163
ClinVar variants
13
Pubs (1 yr)
1.6
Missense Z
0.53
LOEUF
Clinical Summary— SLC5A6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 94 VUS of 163 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.006
Z-score 3.61
OE 0.31 (0.19–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.63Z-score
OE missense 0.76 (0.69–0.84)
291 obs / 380.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.19–0.53)
0≤0.351.4
Missense OE0.76 (0.69–0.84)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 10 / 32.0Missense obs/exp: 291 / 380.5Syn Z: 0.21
GOFDN
DN
0.80top 25%
GOF
0.84top 5%
LOF
0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

163 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic8
VUS94
Likely Benign29
Benign8
Conflicting4
20
Pathogenic
8
Likely Pathogenic
94
VUS
29
Likely Benign
8
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
17
0
20
Likely Pathogenic
5
1
2
0
8
VUS
0
76
16
2
94
Likely Benign
0
22
1
6
29
Benign
0
2
1
5
8
Conflicting
—4
Total61033713163

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

SLC5A6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC5A6-related neurodevelopmental disorder

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients