SLC25A46

Chr 5AR

solute carrier family 25 member 46

Also known as: HMSN6B, PCH1E

The protein is a transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization by promoting mitochondrial fission and regulating the MICOS complex assembly, which is essential for mitochondrial cristae biogenesis and dynamics. Mutations cause autosomal recessive hereditary motor and sensory neuropathy type VIB and pontocerebellar hypoplasia type 1E through disruption of mitochondrial fission and formation of hyperfilamentous mitochondria.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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 OE0.55 (0.340.91)
00.351.4
Missense OE0.97 (0.871.08)
00.61.4
Synonymous OE1.00
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

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.

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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗