SLC25A24

Chr 1AD

solute carrier family 25 member 24

Also known as: APC1, SCAMC-1, SCAMC1

NCBI Gene: 29957 ENSG00000085491 UniProt: Q6NUK1 OMIM: 608744

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a carrier protein that transports ATP-Mg exchanging it for phosphate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 1.131 OMIM phenotype

Clinical Summary— SLC25A24

🧬

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.

📋

ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 114 VUS of 214 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — SLC25A24

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.05

OE 0.78 (0.55–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.82Z-score

OE missense 0.86 (0.77–0.96)

220 obs / 257.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.55–1.13)

0≤0.351.4

Missense OE?0.86 (0.77–0.96)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

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

This gene — mechanism propensity

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 entitie1

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

References

1.PMID 30329211 ↗

ClinVar Variant Classifications

214 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS114

Likely Benign40

Benign47

Conflicting5

Pathogenic

Likely Pathogenic

114

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	1	0	0	1
Likely Pathogenic	0	2	0	0	2
VUS	9	102	2	1	114
Likely Benign	4	8	12	16	40
Benign	0	5	34	8	47
Conflicting	—				5
Total	13	118	48	25	209

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap SLC25A24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →