SLC5A3

Chr 21

solute carrier family 5 member 3

Also known as: BCW2, SMIT, SMIT1, SMIT2

NCBI Gene: 6526 ENSG00000198743 UniProt: P53794 OMIM: 600444

Enables myo-inositol:sodium symporter activity; potassium channel regulator activity; and transmembrane transporter binding activity. Predicted to be involved in several processes, including inositol metabolic process; monosaccharide transmembrane transport; and myo-inositol import across plasma membrane. Predicted to act upstream of or within several processes, including positive regulation of protein localization to membrane; positive regulation of reactive oxygen species biosynthetic process; and regulation of respiratory gaseous exchange. Located in perinuclear region of cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.32

Clinical Summary— SLC5A3

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

42 VUS of 43 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.967

Z-score 3.66

OE 0.10 (0.04–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.76Z-score

OE missense 0.61 (0.55–0.68)

247 obs / 403.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.32)

0≤0.351.4

Missense OE?0.61 (0.55–0.68)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 2 / 19.4Missense obs/exp: 247 / 403.0Syn Z: -1.55

This gene — mechanism propensity

0.5379th %ile

GOF

0.6637th %ile

LOF

0.49top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.32

GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	42	0	42
Likely Benign	0	1	1
Benign	0	0	0
Total	42	1	43

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

View in ClinVar →

63 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap SLC5A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →