SLC25A24

Chr 1AD

solute carrier family 25 member 24

Also known as: APC1, SCAMC-1, SCAMC1

This protein functions as an antiporter that transports adenyl nucleotides across the inner mitochondrial membrane and regulates the mitochondrial matrix adenyl nucleotide pool to meet cellular energetic demands. Mutations cause Fontaine progeroid syndrome, which follows autosomal dominant inheritance. The syndrome involves premature aging features and affects multiple organ systems.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.131 OMIM phenotype
Clinical SummarySLC25A24
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Gene-Disease Validity (ClinGen)
Fontaine progeroid syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — SLC25A24
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
1.13LOEUF
pLI 0.000
Z-score 1.05
OE 0.78 (0.551.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.82Z-score
OE missense 0.86 (0.770.96)
220 obs / 257.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.551.13)
00.351.4
Missense OE0.86 (0.770.96)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 21 / 26.9Missense obs/exp: 220 / 257.2Syn Z: -0.66
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC25A24-related hypertrichosis, progeroid appearance, and mitochondrial dysfunction (Gorlin-Chaudhry-Moss syndrome )OTHERAD
DN
0.76top 25%
GOF
0.73top 25%
LOF
0.3162th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFExome sequencing uncovered a heterozygous mutation in SLC25A24 (NM_013386: c.650G>A: p.R217H) that encodes for the calcium-binding mitochondrial carrier protein SCaMC-1. This gain-of-function variant has been previously associated with Fontaine syndrome and Gorlin-Chaudhry-Moss syndrome, two entitiePMID:30329211

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC25A24 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC