SLC25A1

Chr 22AR

solute carrier family 25 member 1

Also known as: CIC, CMS23, CTP, D2L2AD, SEA, SLC20A3

The protein transports citrate across the inner mitochondrial membrane as part of the citrate-malate antiporter system. Autosomal recessive mutations cause combined D-2- and L-2-hydroxyglutaric aciduria and congenital myasthenic syndrome type 23 with presynaptic dysfunction. The pathogenic mechanism appears to involve dominant-negative effects that disrupt normal mitochondrial citrate transport.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.652 OMIM phenotypes
Clinical SummarySLC25A1
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📖
GeneReview available — SLC25A1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.059
Z-score 2.58
OE 0.31 (0.160.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.24Z-score
OE missense 0.74 (0.640.85)
128 obs / 174.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.160.65)
00.351.4
Missense OE0.74 (0.640.85)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 5 / 16.2Missense obs/exp: 128 / 174.0Syn Z: -1.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC25A1-related neurometabolic disorderLOFAR

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

DN
0.84top 10%
GOF
0.75top 25%
LOF
0.2971th %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

SLC25A1 · 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
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