SLC25A24

Summary

SLC25A24 (solute carrier family 25 member 24, HGNC:20662) is a protein-coding gene on chromosome 1p13.3, encoding Mitochondrial adenyl nucleotide antiporter SLC25A24 (Q6NUK1). Electroneutral antiporter that mediates the transport of adenyl nucleotides through the inner mitochondrial membrane.

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.

Source: NCBI Gene 29957 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fontaine progeroid syndrome (Definitive, ClinGen)
• GWAS associations: 15
• Clinical variants (ClinVar): 204 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 126
• MANE Select transcript: NM_013386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20662
Approved symbol	SLC25A24
Name	solute carrier family 25 member 24
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp586G0123, APC1, SCAMC1, SCAMC-1
Ensembl gene	ENSG00000085491
Ensembl biotype	protein_coding
OMIM	608744
Entrez	29957

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 nonsense_mediated_decay

ENST00000264128, ENST00000370041, ENST00000565488, ENST00000569674, ENST00000648874, ENST00000856697, ENST00000856698, ENST00000926498, ENST00000948780, ENST00000948781, ENST00000948782

RefSeq mRNA: 2 — MANE Select: NM_013386 NM_013386, NM_213651

CCDS: CCDS41361, CCDS786

Canonical transcript exons

ENST00000565488 — 10 exons

Exon	Start	End
ENSE00000544990	108185828	108185954
ENSE00000782887	108181941	108182028
ENSE00002581024	108199956	108200343
ENSE00002591664	108134043	108136837
ENSE00003505488	108143543	108143710
ENSE00003554157	108161182	108161293
ENSE00003571681	108154983	108155135
ENSE00003633095	108157462	108157620
ENSE00003670744	108139058	108139208
ENSE00003673733	108148279	108148386

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 94.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.7399 / max 354.5567, expressed in 1805 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13638	15.7397	1783
13636	10.9654	1680
13639	4.7740	1622
13637	2.8130	1341
13640	0.4418	222
13635	0.0060	2

Top tissues by expression

138 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	94.59	gold quality
duodenum	UBERON:0002114	94.26	gold quality
islet of Langerhans	UBERON:0000006	93.10	gold quality
monocyte	CL:0000576	92.05	gold quality
calcaneal tendon	UBERON:0003701	91.97	gold quality
endometrium	UBERON:0001295	91.96	gold quality
leukocyte	CL:0000738	91.65	gold quality
mucosa of transverse colon	UBERON:0004991	90.73	gold quality
smooth muscle tissue	UBERON:0001135	90.08	gold quality
placenta	UBERON:0001987	88.54	gold quality
gall bladder	UBERON:0002110	88.48	gold quality
transverse colon	UBERON:0001157	88.23	gold quality
vermiform appendix	UBERON:0001154	87.56	gold quality
colonic epithelium	UBERON:0000397	87.50	gold quality
lung	UBERON:0002048	87.26	gold quality
right lung	UBERON:0002167	87.13	gold quality
ventricular zone	UBERON:0003053	86.87	gold quality
small intestine	UBERON:0002108	86.76	gold quality
stromal cell of endometrium	CL:0002255	86.66	gold quality
adrenal tissue	UBERON:0018303	86.61	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.44	gold quality
intestine	UBERON:0000160	86.33	gold quality
adipose tissue	UBERON:0001013	86.08	gold quality
colon	UBERON:0001155	85.82	gold quality
upper lobe of left lung	UBERON:0008952	85.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.62	gold quality
lymph node	UBERON:0000029	85.60	gold quality
left coronary artery	UBERON:0001626	85.47	gold quality
omental fat pad	UBERON:0010414	85.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	409.47
E-ANND-3	no	3.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting SLC25A24, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 11)

• SCaMC-1 is the human orthologue of the rabbit Efinal protein, which was reported to be located in peroxisomes (PMID:15054102)
• identification of three isoforms of the mitochondrial ATP-Mg/Pi carrier APC1, APC2 and APC3; they are most likely responsible for the net uptake or efflux of adenine nucleotides into or from the mitochondria (PMID:15123600)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• N-terminal EF hands form a self-sequestered compact calmodulin like Ca-sensor in the presence of Ca2+ (PMID:24332718)
• Genetic analyses in human and mouse models revealed the importance of SLC25A24/Slc25a24 in the regulation of body fat mass and adipogenesis. (PMID:25599384)
• The SLC25A24 mutations induce a gain of pathological function. (PMID:29100093)
• The SLC25A24 mutations lead to impaired mitochondrial ATP synthesis. (PMID:29100094)
• This study confirms implication of the ACP1 gene in the treatment-related osteonecrosis in childhood acute lymphoblastic leukemia (ALL) and identifies novel, potentially causal variant of this complication. (PMID:31686588)
• SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study. (PMID:34561420)
• Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling. (PMID:35241150)
• Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism. (PMID:38980211)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc25a24	ENSMUSG00000040322
rattus_norvegicus	Slc25a24	ENSRNOG00000020470

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), SLC25A11 (ENSG00000108528), UCP1 (ENSG00000109424), SLC25A36 (ENSG00000114120), SLC25A12 (ENSG00000115840), SLC25A2 (ENSG00000120329), SLC25A51 (ENSG00000122696), SLC25A16 (ENSG00000122912), SLC25A35 (ENSG00000125434), SLC25A19 (ENSG00000125454), SLC25A23 (ENSG00000125648), SLC25A47 (ENSG00000140107), SLC25A52 (ENSG00000141437), SLC25A38 (ENSG00000144659), SLC25A26 (ENSG00000144741), SLC25A48 (ENSG00000145832), SLC25A37 (ENSG00000147454), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

Mitochondrial adenyl nucleotide antiporter SLC25A24 — Q6NUK1 (reviewed: Q6NUK1)

Alternative names: Mitochondrial ATP-Mg/Pi carrier protein 1, Mitochondrial Ca(2+)-dependent solute carrier protein 1, Short calcium-binding mitochondrial carrier protein 1, Solute carrier family 25 member 24

All UniProt accessions (4): Q6NUK1, A0A3B3IU96, H3BMI3, J3KN42

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral antiporter that mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenyl nucleotide pool, could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides. May play a role in protecting cells against oxidative stress-induced cell death, by buffering calcium levels in the mitochondrial matrix through the formation of calcium-phosphate precipitates.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed in all tissues tested. Highly expressed in testis, expressed at intermediate level in small intestine and pancreas, and weakly expressed in kidney, spleen, liver, skeletal muscle and heart.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by an increase in cytosolic calcium levels that induces a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport. When calcium levels are high, the amphipathic alpha-helix of the linker region is bound to a cleft in the N-terminal regulatory domain, allowing substrate transport by the carrier domain. When calcium levels drop, the cleft closes and the amphipathic alpha-helix is released to bind to the carrier domain, inhibiting substrate transport. Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple and tannic acid.

Domain organisation. The regulatory N-terminal domain/NTD, formed of two pairs of fused calcium-binding EF-hands, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity. The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity. Linker region/H9 could directly block the transport of substrates across the transporter.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NUK1-1	1	yes
Q6NUK1-2	2

RefSeq proteins (2): NP_037518, NP_998816 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002067	MCP	Family
IPR002167	GDC-like	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018108	MCP_transmembrane	Repeat
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153, PF13499

Catalyzed reactions (Rhea), 12 shown:

• Mg(2+)(out) + phosphate(in) + ATP(out) = Mg(2+)(in) + phosphate(out) + ATP(in) (RHEA:65840)
• ADP(out) + phosphate(in) + H(+)(out) = ADP(in) + phosphate(out) + H(+)(in) (RHEA:65844)
• AMP(out) + phosphate(in) = AMP(in) + phosphate(out) (RHEA:70259)
• phosphate(in) + ATP(out) + 2 H(+)(out) = phosphate(out) + ATP(in) + 2 H(+)(in) (RHEA:72035)
• dADP(in) + ADP(out) = dADP(out) + ADP(in) (RHEA:72855)
• Mg(2+)(in) + ADP(out) + ATP(in) + H(+)(out) = Mg(2+)(out) + ADP(in) + ATP(out) + H(+)(in) (RHEA:73659)
• ADP(out) + diphosphate(in) = ADP(in) + diphosphate(out) (RHEA:73671)
• dAMP(in) + ADP(out) + H(+)(out) = dAMP(out) + ADP(in) + H(+)(in) (RHEA:73675)
• 3’-AMP(in) + ADP(out) + H(+)(out) = 3’-AMP(out) + ADP(in) + H(+)(in) (RHEA:73679)
• dAMP(out) + phosphate(in) = dAMP(in) + phosphate(out) (RHEA:73687)
• 3’-AMP(out) + phosphate(in) = 3’-AMP(in) + phosphate(out) (RHEA:73691)
• dADP(out) + phosphate(in) + H(+)(out) = dADP(in) + phosphate(out) + H(+)(in) (RHEA:73695)

UniProt features (72 total): binding site 20, helix 8, topological domain 7, transmembrane region 6, modified residue 5, mutagenesis site 5, strand 5, domain 4, repeat 3, region of interest 3, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4N5X	X-RAY DIFFRACTION	2.1
4ZCU	X-RAY DIFFRACTION	2.1
4ZCV	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUK1-F1	81.55	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 32; 34; 36; 38; 43; 68; 70; 72; 74; 79; 99; 101 …

Post-translational modifications (5): 320, 320, 336, 437, 437

Mutagenesis-validated functional residues (5):

Position	Phenotype
88	reduces atp uptake in the presence of calcium.
158	no significant change in atp uptake in the presence or absence of calcium.
159	reduces atp uptake in the presence of calcium.
161	no significant change in atp uptake in the presence or absence of calcium.
277	increases atp uptake in the presence of calcium.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 545 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GGGTGGRR_PAX4_03, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_NUCLEOTIDE_TRANSPORT, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_RESPONSE_TO_METAL_ION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, FISCHER_G2_M_CELL_CYCLE, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOTIDE_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP

GO Biological Process (9): mitochondrial transport (GO:0006839), ADP transport (GO:0015866), ATP transport (GO:0015867), cellular response to oxidative stress (GO:0034599), adenine nucleotide transport (GO:0051503), cellular response to calcium ion (GO:0071277), mitochondrial ATP transmembrane transport (GO:1990544), obsolete organic anion transport (GO:0015711), transmembrane transport (GO:0055085)

GO Molecular Function (8): adenine nucleotide transmembrane transporter activity (GO:0000295), ATP transmembrane transporter activity (GO:0005347), calcium ion binding (GO:0005509), ATP:phosphate antiporter activity (GO:0140987), ADP:phosphate antiporter activity (GO:0140988), obsolete organic anion transmembrane transporter activity (GO:0008514), antiporter activity (GO:0015297), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adenine nucleotide transport	3
purine ribonucleotide transport	2
ATP transport	2
organophosphate:phosphate antiporter activity	2
cellular anatomical structure	2
intracellular transport	1
response to oxidative stress	1
cellular response to chemical stress	1
purine nucleotide transport	1
response to calcium ion	1
cellular response to metal ion	1
purine-containing compound transmembrane transport	1
nucleotide transmembrane transport	1
transport	1
cellular process	1
purine nucleotide transmembrane transporter activity	1
adenine nucleotide transmembrane transporter activity	1
purine ribonucleotide transmembrane transporter activity	1
metal ion binding	1
ATP transmembrane transporter activity	1
ADP transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A24	GPSM2	P81274	765
SLC25A24	MTCH1	Q9NZJ7	710
SLC25A24	MTCH2	Q9Y6C9	644
SLC25A24	VAV3	Q9UKW4	590
SLC25A24	CALML4	Q96GE6	573
SLC25A24	PLAAT2	Q9NWW9	474
SLC25A24	SLC25A53	Q5H9E4	404
SLC25A24	LAPTM4B	Q86VI4	389
SLC25A24	SLC25A46	Q96AG3	385
SLC25A24	F6RGN5	F6RGN5	364
SLC25A24	GPATCH3	Q96I76	362
SLC25A24	STXBP3	O00186	344
SLC25A24	MCU	Q8NE86	319
SLC25A24	SLC25A6	P12236	318
SLC25A24	RPL9	P32969	315

IntAct

95 interactions, top by confidence:

A	B	Type	Score
ANAPC4	BUB1B	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
MFSD4A	HIP1R	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
COX15	SLC25A3	psi-mi:“MI:0914”(association)	0.530
CHST10	SLC25A24	psi-mi:“MI:0915”(physical association)	0.400
SLC25A24	CKAP4	psi-mi:“MI:0915”(physical association)	0.400
SLC25A24	TOMM40	psi-mi:“MI:0915”(physical association)	0.400
HSD17B11	SLC25A24	psi-mi:“MI:0915”(physical association)	0.400
CHMP4B		psi-mi:“MI:0914”(association)	0.350
	ZW10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (173): SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Co-fractionation), SLC25A24 (Co-fractionation), SLC25A24 (Co-fractionation), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS)

ESM2 similar proteins: A2ASZ8, A2CEQ0, A5PJZ1, B4F8I5, B8ZHC9, F1LX07, F1LZW6, F4HW79, F4JU70, K7VYZ9, O13805, O18757, O65023, O75746, P0C546, Q05AQ3, Q0P483, Q0V7M4, Q19529, Q20799, Q21153, Q5PQ27, Q5RBC8, Q5XH95, Q5XHA0, Q628Z2, Q66L49, Q6C107, Q6GQS1, Q6KCM7, Q6NUK1, Q6NYZ6, Q7T0U6, Q7ZY36, Q7ZYD5, Q86VD7, Q8BH59, Q8BMD8, Q8BVN7, Q8HXW2

Diamond homologs: A0A1D6N272, A1DI57, A2ASZ8, A2CEQ0, A2R5A0, A4RF23, A5PJZ1, B0DK57, B0G159, B2MVX9, B4F8I5, B4FIJ0, B8ZHC9, F1LX07, F4JU70, G2QNH0, K3VFR5, K7VYZ9, O04619, O13844, O18757, O22342, O65023, O94502, O95258, P04709, P0C546, P0CAT2, P0CI40, P12857, P16260, P16261, P27080, P29518, P31167, P31691, P53007, P79110, Q01888, Q05AQ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

204 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	112
Likely benign	39
Benign	39

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
369980	NM_013386.5(SLC25A24):c.649C>T (p.Arg217Cys)	Pathogenic
370032	NM_013386.5(SLC25A24):c.650G>A (p.Arg217His)	Pathogenic
692155	NM_013386.5(SLC25A24):c.758G>C (p.Gly253Ala)	Likely pathogenic

SpliceAI

2072 predictions. Top by Δscore:

Variant	Effect	Δscore
1:108136833:CATGG:C	acceptor_gain	1.0000
1:108136835:TGG:T	acceptor_gain	1.0000
1:108136835:TGGC:T	acceptor_loss	1.0000
1:108136836:GG:G	acceptor_gain	1.0000
1:108136838:C:CC	acceptor_gain	1.0000
1:108136838:C:CG	acceptor_loss	1.0000
1:108139207:AGC:A	acceptor_loss	1.0000
1:108139209:C:CC	acceptor_gain	1.0000
1:108139213:C:CT	acceptor_gain	1.0000
1:108139214:A:T	acceptor_gain	1.0000
1:108148387:C:CC	acceptor_gain	1.0000
1:108154979:TTACC:T	donor_loss	1.0000
1:108154980:TACCT:T	donor_loss	1.0000
1:108155133:AACC:A	acceptor_loss	1.0000
1:108155136:C:CC	acceptor_gain	1.0000
1:108155136:CT:C	acceptor_loss	1.0000
1:108155137:T:C	acceptor_loss	1.0000
1:108157459:CA:C	donor_loss	1.0000
1:108157460:A:AC	donor_gain	1.0000
1:108157460:A:AT	donor_loss	1.0000
1:108157461:C:CA	donor_loss	1.0000
1:108157461:C:CC	donor_gain	1.0000
1:108157461:CCTG:C	donor_gain	1.0000
1:108157617:TTCC:T	acceptor_gain	1.0000
1:108157619:CC:C	acceptor_gain	1.0000
1:108157620:CCTG:C	acceptor_gain	1.0000
1:108157621:C:CC	acceptor_gain	1.0000
1:108157629:A:AC	acceptor_gain	1.0000
1:108157629:A:C	acceptor_gain	1.0000
1:108161175:GACTT:G	donor_loss	1.0000

AlphaMissense

3134 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:108136751:C:G	G446R	1.000
1:108136737:G:C	N450K	0.999
1:108136737:G:T	N450K	0.999
1:108139098:G:C	S403R	0.999
1:108139098:G:T	S403R	0.999
1:108139100:T:G	S403R	0.999
1:108139111:C:T	G399D	0.999
1:108139112:C:G	G399R	0.999
1:108143605:C:G	G346R	0.999
1:108155043:A:C	N254K	0.999
1:108155043:A:T	N254K	0.999
1:108155047:C:T	G253E	0.999
1:108155054:A:G	W251R	0.999
1:108155054:A:T	W251R	0.999
1:108157481:C:G	R217P	0.999
1:108157505:C:G	R209P	0.999
1:108157520:G:T	A204D	0.999
1:108136717:G:T	A457D	0.998
1:108136720:G:T	P456H	0.998
1:108136728:C:A	K453N	0.998
1:108136728:C:G	K453N	0.998
1:108136750:C:A	G446V	0.998
1:108136750:C:T	G446D	0.998
1:108136751:C:A	G446C	0.998
1:108136757:A:C	Y444D	0.998
1:108139093:G:T	P405Q	0.998
1:108139119:G:C	S396R	0.998
1:108139119:G:T	S396R	0.998
1:108139121:T:G	S396R	0.998
1:108143556:A:G	L362P	0.998

dbSNP variants (sampled 300 via entrez): RS1000047304 (1:108150388 G>C), RS1000123048 (1:108173991 G>C), RS1000136226 (1:108182408 T>C), RS1000140428 (1:108138017 A>C), RS1000169046 (1:108159746 GAC>G), RS1000173289 (1:108150568 C>G,T), RS1000300794 (1:108180641 T>A,C,G), RS1000352030 (1:108198061 C>A,G), RS1000441653 (1:108155355 C>A,G), RS1000538823 (1:108143187 G>A), RS1000628821 (1:108199477 C>T), RS1000658460 (1:108185780 G>A,T), RS1000691813 (1:108167668 C>A,T), RS1000747166 (1:108195807 T>A,C), RS1000747518 (1:108136492 T>C)

Disease associations

OMIM: gene MIM:608744 | disease phenotypes: MIM:233500, MIM:612289

GenCC curated gene-disease

Disease	Classification	Inheritance
Fontaine progeroid syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Fontaine progeroid syndrome	Definitive	AD

Mondo (2): Fontaine progeroid syndrome (MONDO:0012853), dementia (MONDO:0001627)

Orphanet (3): Gorlin-Chaudhry-Moss syndrome (Orphanet:2095), Progeroid syndrome, Petty type (Orphanet:2963), Fontaine progeroid syndrome (Orphanet:697101)

HPO phenotypes

126 total (30 of 126 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000059	Hypoplastic labia majora
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000262	Turricephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000444	Convex nasal ridge
HP:0000478	Abnormality of the eye

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002527_2	Eosinophilic esophagitis	7.000000e-07
GCST004608_10	Granulocyte percentage of myeloid white cells	4.000000e-10
GCST004609_180	Monocyte percentage of white cells	6.000000e-09
GCST004610_29	White blood cell count	6.000000e-10
GCST004613_53	Sum neutrophil eosinophil counts	4.000000e-11
GCST004614_114	Granulocyte count	5.000000e-11
GCST004620_3	Sum basophil neutrophil counts	6.000000e-11
GCST004626_2	Myeloid white cell count	4.000000e-10
GCST004629_10	Neutrophil count	7.000000e-11
GCST009391_1908	Metabolite levels	6.000000e-06
GCST009391_552	Metabolite levels	2.000000e-07
GCST90002394_150	Monocyte percentage of white cells	1.000000e-17
GCST90002398_488	Neutrophil count	7.000000e-18
GCST90002399_2	Neutrophil percentage of white cells	2.000000e-10
GCST90002407_665	White blood cell count	5.000000e-15

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0010463	asymmetric dimethylarginine measurement
EFO:0009769	histidine measurement
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003704	Dementia	C10.228.140.380; F03.615.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Mitochondrial nucleotide transporter subfamily

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression, decreases expression	3
Cadmium	increases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Copper Sulfate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC668394	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Pioglitazone	decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Clozapine	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4CW	HCT116-SLC25A24-KO-c3	Cancer cell line	Male
CVCL_D4D9	HCT116-SLC25A24-KO-c4	Cancer cell line	Male
CVCL_TM25	HAP1 SLC25A24 (-) 1	Cancer cell line	Male
CVCL_XT03	HAP1 SLC25A24 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00043849	PHASE4	COMPLETED	Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
NCT00127114	PHASE4	WITHDRAWN	Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)
NCT00164970	PHASE4	COMPLETED	Can Oral Vitamin B12 and Folate Supplementation Preserve Cognitive Function of Patients With Early Dementia?
NCT00177671	PHASE4	COMPLETED	Antidepressant Medication Plus Donepezil for Treating Late-life Depression
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00371059	PHASE4	COMPLETED	Memantine for Agitation in Dementia
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00433121	PHASE4	COMPLETED	Discontinuation of Antipsychotics and Antidepressants Among Patients With BPSD
NCT00450047	PHASE4	COMPLETED	Study on the Efficacy of Speed-Feedback Therapy for Elderly People With Dementia
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00594269	PHASE4	COMPLETED	Dementia Antipsychotics And Antidepressants Discontinuation Study
NCT00626613	PHASE4	UNKNOWN	The Relationship Between Risperdal Treatment and Quality of Life in Patients With Alzheimer’s Disease and Behavioural and Psychological Symptoms of Dementia (BPSD)
NCT00768261	PHASE4	COMPLETED	Corticolimbic Degeneration and Treatment of Dementia
NCT00792662	PHASE4	WITHDRAWN	Improving Function, Quality of Life, Glycemia in Diabetics With Dementia
NCT00814658	PHASE4	COMPLETED	The Use of Galantamine (Reminyl ER) in Patients With MIXed Dementia: Effects on Cognition and Quality of Life
NCT00914095	PHASE4	COMPLETED	Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson’s Disease (PARKGAIT-II)
NCT01012830	PHASE4	UNKNOWN	Huperzine-A to Help With Mental Problems and the Inability to Care for Onself in Patients With Schizophrenia
NCT01109836	PHASE4	COMPLETED	Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke
NCT01340950	PHASE4	COMPLETED	Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
NCT01453127	PHASE4	ENROLLING_BY_INVITATION	DaTSCAN Imaging in Aging and Neurodegenerative Disease
NCT01799941	PHASE4	COMPLETED	Safety, Tolerability and Effectiveness of Nuedexta in the Treatment of Pseudobulbar Affect (PBA)
NCT01825577	PHASE4	TERMINATED	Exploring the Use of Transdermal Methylphenidate to Reduce Fall Risk in Patients With Dementia.
NCT01849042	PHASE4	UNKNOWN	Effect of Memantine Oral Pump on Language in Patients With Probable Alzheimer’s Disease
NCT02267057	PHASE4	COMPLETED	Efficacy of Pain Treatment on Depression in Patients With Dementia
NCT02782429	PHASE4	UNKNOWN	The Role of Ketamine in Preventing Cognitive Dysfunctions in Postoperative Period of Cardiac Surgery
NCT03061006	PHASE4	COMPLETED	Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation
NCT03066518	PHASE4	COMPLETED	Effect of Melatonin on Sleep Quality in Patients Dementia
NCT03221751	PHASE4	TERMINATED	Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI)
NCT03817931	PHASE4	COMPLETED	Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder
NCT04117178	PHASE4	COMPLETED	Monitoring Anti-Dementia Drugs by Serum Levels
NCT04262206	PHASE4	RECRUITING	Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults
NCT04294654	PHASE4	COMPLETED	Vortioxetine in Patients With Depression and Early Dementia
NCT05514106	PHASE4	ENROLLING_BY_INVITATION	MIBG in Aging and Neurologic Disorders
NCT05531591	PHASE4	COMPLETED	RCT of Brain Longitudinal Biomarker Study (OPT-Neuro RCT)
NCT05855863	PHASE4	NOT_YET_RECRUITING	Clinical Study of GKT in Diabetes Related Dementia
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT06662526	PHASE4	NOT_YET_RECRUITING	Lithium for Prevention of Cognitive Declining in Mood Illnesses