SLC5A9

Chr 1

solute carrier family 5 member 9

Also known as: SGLT4

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.36
Clinical SummarySLC5A9
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.36LOEUF
pLI 0.000
Z-score -0.23
OE 1.04 (0.801.36)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.80Z-score
OE missense 0.89 (0.820.97)
380 obs / 426.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.04 (0.801.36)
00.351.4
Missense OE0.89 (0.820.97)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 39 / 37.5Missense obs/exp: 380 / 426.6Syn Z: 0.15
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC5A9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC