SLC25A46

Chr 5AR

solute carrier family 25 member 46

Also known as: HMSN6B, PCH1E

This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.912 OMIM phenotypes
Clinical SummarySLC25A46
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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?
0.91LOEUF
pLI 0.000
Z-score 1.88
OE 0.55 (0.340.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.16Z-score
OE missense 0.97 (0.871.08)
219 obs / 225.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.55 (0.340.91)
00.351.4
Missense OE?0.97 (0.871.08)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 11 / 20.1Missense obs/exp: 219 / 225.8Syn Z: 0.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC25A46-related neuropathy, hereditary motor and sensoryLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.6248th %ile
LOF
0.3941th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC25A46 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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