SLC25A24

protein-coding

solute carrier family 25 member 24, the group of Solute carrier family 25|EF-hand domain containing

Gene summary

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]

MANE transcript

NM_013386.5

Inheritance

AR, AD

ClinVar variants

P:3U:125B:45

Top phenotype

Fontaine progeroid syndrome

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr1:108,134,043-108,200,849

External References & Databases

Ensembl (ENSG00000085491)

Transcript & Mutation Effects

hg38 • Region Span ~66.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Fontaine progeroid syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012853

Submitter: Orphanet

Fontaine progeroid syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012853

Submitter: PanelApp Australia

Fontaine progeroid syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012853

Submitter: ClinGen

SLC25A24 is located in chromosome 1 at 1p13.3 and encodes the solute carrier family 25 (Mitochondrial Carrier, Phosphate Carrier), member 24. Multiple disease entities have been reported in association with this gene. According to criteria outlined by the ClinGen Lumping and Splitting Working Group, there was no evidence of differences in their molecular mechanism and phenotypic spectrum. Therefore, the following disease entities have been lumped into one disease entity (MONDO:0012853): Gorlin-Chaudhry-Moss syndrome, Fontaine–Farriaux syndrome (FFS), and Fontaine progeroid syndrome. Petty–Laxova–Wiedemann syndrome was not included in this entity due to lack of molecular diagnosis (PMIDs: 2309786,19725131, 20583180). SLC25A24 was first reported in connection with SLC25A24-related Fontaine Progeroid syndrome in 2017 (PMID: 29100093; Ehmke et al. 2017). Fifteen probands across seven publications have been included in this curation (PMIDs: 38980211; 32732226; 31231135; 31775791; 30329211; 29100094; 29100093). Pathogenic SLC25A24 variants are missense and de novo, consisting of p.Arg217His (more frequent) or p.Arg217Cys. The mechanism of disease is gain-of-function where both p.Arg217Cys and p.Arg217His narrow the substrate cavity of the protein and disrupt transporter dynamics, leading to impaired mitochondrial ATP synthesis, increased mitochondrial membrane potential (hyperpolarization), and increased proton leak (PMID: 38980211). This gene-disease relationship is also supported by functional alteration assays, biochemical evidence, and a mouse model (PMIDs: 28350015; 25599384; 29100094; 29100093). In summary, there is definitive evidence supporting the relationship between SLC25A24 and autosomal dominant SLC25A24-related Fontaine Progeroid syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the Craniofacial Malformations Gene Curation Expert Panel on the meeting date 09/18/2025 (SOP Version 11).

Fontaine progeroid syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012853

Submitter: G2P

Fontaine progeroid syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012853

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Fontaine progeroid syndromeAD

Manifestation: Craniofacial; Dermatologic; Genitourinary; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21216154; 29100093; 29100094

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC25A24 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 98

Inborn genetic diseasesTotal: 84

Fontaine progeroid syndromeTotal: 17

SLC25A24-related disorderTotal: 15

not specifiedTotal: 13

Bilateral tonic-clonic seizureTotal: 2

DementiaTotal: 2

Multiple congenital anomalies/dysmorphic syndrome-intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013386.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	22 clinvar	4 clinvar	27
missense	1 clinvar	2 clinvar	112 clinvar	11 clinvar	3 clinvar	129
nonsense			4 clinvar	2 clinvar		6
start loss			1 clinvar			1
frameshift			3 clinvar	3 clinvar		6
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	2	125	38	7	173

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013386.5	RefSeq	NP_037518.3	10	MANE Select
ENST00000565488.6	Ensembl	ENSP00000457733.1	10	MANE Select
NM_213651.3	RefSeq	NP_998816.1	10	Standard
ENST00000264128.13	Ensembl	ENSP00000264128.9	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

mitochondrial transport
regulation of cell death
ATP transport
cellular response to oxidative stress
transmembrane transport

Molecular Function

ATP transmembrane transporter activity
calcium ion binding

Cellular Component

mitochondrion
mitochondrial inner membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000565488
Coding exons: 10
Length: 66814
Individuals with no LoFs: 125537
Homozygous LoFs: 0
Heterozygous LoFs: 211
Defined: 125748
p: 0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.824	220	257	0.855	0.0000125	3109
Missense (PolyPhen)		65	94.035	0.69123		1186
Synonymous	-0.663	99	91.0	1.09	0.00000462	901
Loss of Function	1.05	21	26.9	0.782	0.00000144	302

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.0028	0.0027	notable
East Asian	0.0017	0.0017	notable
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.00055	0.00055	rare
South Asian	0.00092	0.00091	rare
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-dependent mitochondrial solute carrier. Mediates the reversible, electroneutral exchange of Mg-ATP or Mg-ADP against phosphate ions, catalyzing the net uptake or efflux of adenine nucleotides across the mitochondrial inner membrane. Nucleotide transport is inactive when cytosolic calcium levels are low, and is activated by an increase in cytosolic calcium levels. May play a role in protecting cells against oxidative stress- induced cell death, probably by promoting the formation of calcium-phosphate precipitates in the mitochondrial matrix, and thereby buffering calcium levels in the mitochondrial matrix. {ECO:0000269|PubMed:15123600, ECO:0000269|PubMed:22015608, ECO:0000269|PubMed:29100093}.;
Disease: DISEASE: Fontaine progeroid syndrome (FPS) [MIM:612289]: An autosomal dominant progeroid disorder characterized by prenatal and postnatal growth retardation, decreased subcutaneous fat tissue, wrinkled skin, an aged appearance since birth, an abnormal scalp hair pattern, sparse hair, hypoplastic distal phalanges with hypoplastic nails, a widely open anterior fontanel, facial dysmorphisms, and craniosynostosis. Early death is observed in some patients. {ECO:0000269|PubMed:29100093}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.876
RVIS EVS: -0.71
RVIS percentile EVS: 14.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.248

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium