SLC5A9

Chr 1

solute carrier family 5 member 9

Also known as: SGLT4

NCBI Gene: 200010 ENSG00000117834 UniProt: Q2M3M2

The SLC5A9 protein is an electrogenic sodium-coupled sugar symporter that transports D-mannose and possibly D-fructose and D-glucose across the plasma membrane, driven by the transmembrane sodium electrochemical gradient. Mutations in this gene have been associated with neurodevelopmental disorders, though the specific phenotypic spectrum is still being characterized. The gene shows moderate constraint against loss-of-function variants (LOEUF 1.359), suggesting some tolerance to such mutations.

ResearchSummary from RefSeq, UniProt

Predicted to enable D-glucose:sodium symporter activity. Predicted to be involved in hexose transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.36

Clinical Summary— SLC5A9

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

110 VUS of 148 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score -0.23

OE 1.04 (0.80–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.80Z-score

OE missense 0.89 (0.82–0.97)

380 obs / 426.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.80–1.36)

0≤0.351.4

Missense OE?0.89 (0.82–0.97)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 39 / 37.5Missense obs/exp: 380 / 426.6Syn Z: 0.15

This gene — mechanism propensity

0.74top 25%

GOF

0.79top 25%

LOF

0.2583th %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

148 submitted variants in ClinVar

ClinVar

Classification Summary

VUS110

Likely Benign14

Benign16

110

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	108	0	0	110
Likely Benign	0	6	2	6	14
Benign	1	10	0	5	16
Total	3	124	2	11	140

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap SLC5A9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →