SLC5A10

Chr 17

solute carrier family 5 member 10

Also known as: SGLT-5, SGLT5

NCBI Gene: 125206 ENSG00000154025 UniProt: A0PJK1

The protein functions as a kidney-specific sodium-dependent transporter that reabsorbs D-mannose and D-fructose from glomerular filtrate across the renal brush border membrane. Mutations in this gene cause autosomal recessive congenital mannose-losing nephropathy, characterized by excessive urinary mannose excretion and associated metabolic complications. The gene shows low constraint against loss-of-function variants (LOEUF 1.039), consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq, UniProt

This gene is a member of the sodium/glucose transporter family. Members of this family are sodium-dependent transporters and can be divided into two subfamilies based on sequence homology, one that co-transports sugars and the second that transports molecules such as ascorbate, choline, iodide, lipoate, monocaroboxylates, and pantothenate. The protein encoded by this gene has the highest affinity for mannose and has been reported to be most highly expressed in the kidney. This protein may function as a kidney-specific, sodium-dependent mannose and fructose co-transporter. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.04

Clinical Summary— SLC5A10

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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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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?

1.04LOEUF

pLI 0.000

Z-score 1.37

OE 0.74 (0.54–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.82Z-score

OE missense 0.89 (0.81–0.97)

362 obs / 408.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.54–1.04)

0≤0.351.4

Missense OE?0.89 (0.81–0.97)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 25 / 33.6Missense obs/exp: 362 / 408.7Syn Z: 0.01

This gene — mechanism propensity

0.79top 25%

GOF

0.80top 10%

LOF

0.2190th %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.