SLC35F3

Chr 1

solute carrier family 35 member F3

The protein mediates thiamine transport across membranes. Mutations cause autosomal recessive thiamine metabolism dysfunction, characterized by neurological deterioration and metabolic abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.535), consistent with its essential role in cellular thiamine homeostasis.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.54
Clinical SummarySLC35F3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.100
Z-score 3.18
OE 0.27 (0.150.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.71Z-score
OE missense 0.72 (0.650.81)
220 obs / 303.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.150.54)
00.351.4
Missense OE0.72 (0.650.81)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 6 / 22.1Missense obs/exp: 220 / 303.8Syn Z: -0.07
DN
0.7035th %ile
GOF
0.75top 25%
LOF
0.3065th %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

SLC35F3 · 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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