SLC25A26

Chr 3AR

solute carrier family 25 member 26

Also known as: COXPD28, SAMC

NCBI Gene: 115286 ENSG00000144741 UniProt: Q70HW3 OMIM: 611037

The protein functions as a mitochondrial antiporter that exchanges S-adenosyl-L-methionine (the primary cellular methyl donor) for S-adenosyl-L-homocysteine across the inner mitochondrial membrane. Biallelic mutations cause combined oxidative phosphorylation deficiency 28, inherited in an autosomal recessive pattern. This gene shows relatively low constraint to loss-of-function variation (LOEUF 1.236), indicating some tolerance to heterozygous inactivation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.241 OMIM phenotype

Clinical Summary— SLC25A26

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 74 VUS of 205 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.87

OE 0.76 (0.49–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.39Z-score

OE missense 1.10 (0.96–1.26)

144 obs / 131.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.49–1.24)

0≤0.351.4

Missense OE?1.10 (0.96–1.26)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 12 / 15.7Missense obs/exp: 144 / 131.4Syn Z: 0.51

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC25A26-related intra-mitochondrial methylation deficiencyLOFAR

This gene — mechanism propensity

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

0.85top 5%

GOF

0.71top 25%

LOF

0.2485th %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

205 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS74

Likely Benign57

Benign56

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	4	0	0	4
Likely Pathogenic	3	0	0	0	3
VUS	3	60	9	2	74
Likely Benign	0	6	34	17	57
Benign	0	3	51	2	56
Conflicting	—				2
Total	6	73	94	21	196

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

3 pathogenic / likely-pathogenic (of 7) ClinVar copy-number / structural variants overlap SLC25A26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →