SLC25A26

Chr 3AR

solute carrier family 25 member 26

Also known as: COXPD28, SAMC

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 28MIM #616794
AR
0
Active trials
1
Pubs (1 yr)
12
P/LP submissions
40%
P/LP missense
1.24
LOEUF
LOF
Mechanism· G2P
Clinical SummarySLC25A26
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 77 VUS of 211 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.000
Z-score 0.87
OE 0.76 (0.491.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.39Z-score
OE missense 1.10 (0.961.26)
144 obs / 131.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.491.24)
00.351.4
Missense OE1.10 (0.961.26)
00.61.4
Synonymous OE0.91
01.21.6
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

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

DN
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

211 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS77
Likely Benign57
Benign56
Conflicting2
8
Pathogenic
2
Likely Pathogenic
77
VUS
57
Likely Benign
56
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
4
0
8
Likely Pathogenic
2
0
0
0
2
VUS
2
60
13
2
77
Likely Benign
0
5
35
17
57
Benign
0
3
51
2
56
Conflicting
2
Total47210321202

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A26 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC