SLC25A32

Chr 8AR

solute carrier family 25 member 32

Also known as: GLYB, MFT, MFTC, RREI

NCBI Gene: 81034 ENSG00000164933 UniProt: Q9H2D1 OMIM: 138480

The protein facilitates flavin adenine dinucleotide (FAD) transport across the mitochondrial inner membrane, where FAD serves as a redox cofactor for fatty acid beta-oxidation, amino acid metabolism, and mitochondrial electron transport. Mutations cause autosomal recessive exercise intolerance that responds to riboflavin supplementation. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the P(I/L)W subfamily of mitochondrial carrier family transport proteins. The encoded protein transports folate across the inner mitochondrial membrane. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.321 OMIM phenotype

Clinical Summary— SLC25A32

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.59

OE 0.84 (0.56–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.92 (0.81–1.05)

165 obs / 178.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.56–1.32)

0≤0.351.4

Missense OE?0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 14 / 16.6Missense obs/exp: 165 / 178.9Syn Z: -1.31

This gene — mechanism propensity

0.79top 25%

GOF

0.6931th %ile

LOF

0.3356th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

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.