SLC25A25

Summary

SLC25A25 (solute carrier family 25 member 25, HGNC:20663) is a protein-coding gene on chromosome 9q34.11, encoding Mitochondrial adenyl nucleotide antiporter SLC25A25 (Q6KCM7). Electroneutral antiporter that most probably mediates the transport of adenyl nucleotides through the inner mitochondrial membrane.

The protein encoded by this gene belongs to the family of calcium-binding mitochondrial carriers, with a characteristic mitochondrial carrier domain at the C-terminus. These proteins are found in the inner membranes of mitochondria, and function as transport proteins. They shuttle metabolites, nucleotides and cofactors through the mitochondrial membrane and thereby connect and/or regulate cytoplasm and matrix functions. This protein may function as an ATP-Mg/Pi carrier that mediates the transport of Mg-ATP in exchange for phosphate, and likely responsible for the net uptake or efflux of adenine nucleotides into or from the mitochondria. Alternatively spliced transcript variants encoding different isoforms with a common C-terminus but variable N-termini have been described for this gene.

Source: NCBI Gene 114789 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total — 1 pathogenic
• MANE Select transcript: NM_001330988

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20663
Approved symbol	SLC25A25
Name	solute carrier family 25 member 25
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1896, PCSCL, MCSC
Ensembl gene	ENSG00000148339
Ensembl biotype	protein_coding
OMIM	608745
Entrez	114789

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000373064, ENST00000373066, ENST00000373068, ENST00000373069, ENST00000432073, ENST00000445012, ENST00000466983, ENST00000472769, ENST00000682371, ENST00000682638, ENST00000683206, ENST00000684304, ENST00000971446, ENST00000971447, ENST00000971448

RefSeq mRNA: 6 — MANE Select: NM_001330988 NM_001006641, NM_001006642, NM_001265614, NM_001330988, NM_001387057, NM_052901

CCDS: CCDS35151, CCDS48031, CCDS59146, CCDS6890, CCDS83420

Canonical transcript exons

ENST00000373069 — 11 exons

Exon	Start	End
ENSE00000984470	128105729	128105881
ENSE00000984471	128106150	128106257
ENSE00000984472	128106353	128106520
ENSE00000984473	128107029	128107179
ENSE00001109785	128102080	128102115
ENSE00001109786	128103681	128103839
ENSE00001459447	128107260	128109245
ENSE00001516121	128068232	128068580
ENSE00003497783	128101096	128101222
ENSE00003580484	128102370	128102481
ENSE00003591506	128101309	128101396

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6574 / max 310.3333, expressed in 1815 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98694	15.9967	1794
98702	3.2746	976
98701	2.7032	1105
98696	1.4373	390
98700	0.7209	451
98699	0.3060	126
98698	0.0787	59
98695	0.0739	19
98697	0.0662	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	97.35	gold quality
kidney epithelium	UBERON:0004819	96.83	gold quality
right lobe of liver	UBERON:0001114	96.31	gold quality
gall bladder	UBERON:0002110	95.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.79	gold quality
left uterine tube	UBERON:0001303	94.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.01	gold quality
gastrocnemius	UBERON:0001388	93.63	gold quality
liver	UBERON:0002107	93.46	gold quality
adenohypophysis	UBERON:0002196	92.91	gold quality
muscle of leg	UBERON:0001383	92.83	gold quality
pituitary gland	UBERON:0000007	92.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.12	gold quality
epithelial cell of pancreas	CL:0000083	92.04	silver quality
vena cava	UBERON:0004087	91.98	gold quality
pancreatic ductal cell	CL:0002079	91.67	silver quality
body of pancreas	UBERON:0001150	91.29	gold quality
nasal cavity epithelium	UBERON:0005384	90.93	silver quality
smooth muscle tissue	UBERON:0001135	90.87	gold quality
ectocervix	UBERON:0012249	90.44	gold quality
omental fat pad	UBERON:0010414	90.15	gold quality
peritoneum	UBERON:0002358	90.13	gold quality
trachea	UBERON:0003126	90.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.88	gold quality
endocervix	UBERON:0000458	89.84	gold quality
uterine cervix	UBERON:0000002	89.50	gold quality
muscle tissue	UBERON:0002385	89.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.32	gold quality
body of tongue	UBERON:0011876	89.25	gold quality
skeletal muscle tissue	UBERON:0001134	89.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.57
E-MTAB-10137	no	235.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting SLC25A25, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
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-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1271-5P	99.91	71.99	1972

Literature-anchored findings (GeneRIF, showing 6)

• may play an important role in regulating the function of hepatocytes rather than in differentiation in vivo (PMID:12645546)
• SCaMC-2, has four variants generated by alternative splicing, resulting in proteins with a common C terminus but with variations in their N-terminal halves, including the loss of one to three EF-hand motifs (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 [APC3] (PMID:15123600)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• FOXD3 acts as a repressor of the mitochondrial S-adenosylmethionine carrier (SLC25A26) gene expression in cancer cells. (PMID:30076902)
• Exome sequencing identifies a disease variant of the mitochondrial ATP-Mg/Pi carrier SLC25A25 in two families with kidney stones. (PMID:34346195)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a25a	ENSDARG00000010572
danio_rerio	slc25a25b	ENSDARG00000035468
danio_rerio	slc25a24l	ENSDARG00000038977
mus_musculus	Slc25a25	ENSMUSG00000026819
rattus_norvegicus	Slc25a25	ENSRNOG00000014338

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), 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), 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 SLC25A25 — Q6KCM7 (reviewed: Q6KCM7)

Alternative names: Mitochondrial ATP-Mg/Pi carrier protein 3, Mitochondrial Ca(2+)-dependent solute carrier protein 3, Short calcium-binding mitochondrial carrier protein 2, Solute carrier family 25 member 25

All UniProt accessions (5): Q6KCM7, A0A804HI56, A0A804HLB0, F8WEY9, H7C4Z4

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral antiporter that most probably mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Has calcium-dependent ATP-magnesium/inorganic phosphate antiporter activity. Could also have a broader specificity for adenyl nucleotides. By regulating the mitochondrial matrix adenyl nucleotide pool, could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways. Acts downstream of Ca(2+)-permeable cation channel PKD2/TRPP2 and it is likely that PKD2-mediated Ca(2+) signaling activates SLC25A25 antiporter activity. Required for left-right pattern specification.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Widely expressed. Expressed in fetal and adult liver, skeletal muscle, testis, ovary, hippocampus and caudate nucleus. Expressed in all tissues tested. Expression is restricted to kidney and lung.

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.

Domain organisation. The regulatory N-terminal domain/NTD 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 (6)

UniProt ID	Names	Canonical?
Q6KCM7-1	1, SCaMC-2a	yes
Q6KCM7-2	2, SCaMC-2b
Q6KCM7-3	3
Q6KCM7-4	4, SCaMC-2c
Q6KCM7-5	5
Q6KCM7-6	6, SCaMC-2d

RefSeq proteins (6): NP_001006642, NP_001006643, NP_001252543, NP_001317917, NP_001373986, NP_443133 (=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
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153, PF13499, PF13833

Catalyzed reactions (Rhea), 1 shown:

• Mg(2+)(out) + phosphate(in) + ATP(out) = Mg(2+)(in) + phosphate(out) + ATP(in) (RHEA:65840)

UniProt features (35 total): topological domain 7, transmembrane region 6, binding site 5, splice variant 4, domain 3, repeat 3, region of interest 3, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6KCM7-F1	73.65	0.26

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 (5): 60; 62; 64; 66; 71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): ATF_B, GGGACCA_MIR133A_MIR133B, NKX25_02, GOBP_RESPONSE_TO_DIETARY_EXCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_RESPONSE_TO_FOOD, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (12): response to dietary excess (GO:0002021), response to activity (GO:0014823), ADP transport (GO:0015866), ATP transport (GO:0015867), response to food (GO:0032094), multicellular organism growth (GO:0035264), camera-type eye development (GO:0043010), cellular respiration (GO:0045333), ATP metabolic process (GO:0046034), adipose tissue development (GO:0060612), calcium ion transmembrane transport (GO:0070588), transmembrane transport (GO:0055085)

GO Molecular Function (5): ATP transmembrane transporter activity (GO:0005347), calcium ion binding (GO:0005509), ATP:phosphate antiporter activity (GO:0140987), antiporter activity (GO:0015297), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to nutrient levels	2
purine ribonucleotide transport	2
adenine nucleotide transport	2
energy homeostasis	1
response to stimulus	1
response to chemical	1
multicellular organismal process	1
developmental growth	1
eye development	1
energy derivation by oxidation of organic compounds	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
animal organ development	1
connective tissue development	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
transport	1
cellular process	1
adenine nucleotide transmembrane transporter activity	1
purine ribonucleotide transmembrane transporter activity	1
ATP transport	1
metal ion binding	1
ATP transmembrane transporter activity	1
organophosphate:phosphate antiporter 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
cellular anatomical structure	1

Protein interactions and networks

STRING

1372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A25	MTCH1	Q9NZJ7	664
SLC25A25	MTCH2	Q9Y6C9	656
SLC25A25	CALML6	Q8TD86	573
SLC25A25	MICU1	Q9BPX6	524
SLC25A25	MCU	Q8NE86	498
SLC25A25	MICU2	Q8IYU8	493
SLC25A25	TIMM21	Q9BVV7	451
SLC25A25	TIMM22	Q9Y584	447
SLC25A25	TIMM8A	O60220	447
SLC25A25	TIMM50	Q3ZCQ8	438
SLC25A25	NDUFA8	P51970	436
SLC25A25	NDUFB7	P17568	427
SLC25A25	NDUFB10	O96000	426
SLC25A25	SLC25A5	P05141	420
SLC25A25	BBC3	Q96PG8	417

IntAct

45 interactions, top by confidence:

A	B	Type	Score
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
PLEC	SLC25A25	psi-mi:“MI:0915”(physical association)	0.400
SLC25A25	MTCL2	psi-mi:“MI:0915”(physical association)	0.400
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
CD80	POTEF	psi-mi:“MI:0914”(association)	0.350
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
AQP3	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC18A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC25A25	METAP2	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC1A1	UBXN8	psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
VIPR1	SLC33A1	psi-mi:“MI:0914”(association)	0.350
FCN3	MAP2K7	psi-mi:“MI:0914”(association)	0.350
GPR55	SCAMP3	psi-mi:“MI:0914”(association)	0.350
TMEM150A	ACSL4	psi-mi:“MI:0914”(association)	0.350
KLK5	LRP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): SLC25A25 (Affinity Capture-RNA), SLC25A25 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), STK38L (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS), SLC25A25 (Proximity Label-MS), SLC25A25 (Proximity Label-MS), SLC25A25 (Proximity Label-MS), SLC25A25 (Proximity Label-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, A3LVX1, A4RF23, A5DIS9, A5DX39, A6RF73, A6SL61, A7ER02, A7TIQ0, B4FIJ0, F4JU70, O04619, O94370, O95847, P29518, P49382, Q05AQ3, Q0CEN9, Q0P483, Q0UUH1, Q1E7P0, Q29RM1, Q2HFL6, Q2UCW8, Q3ZBJ8, Q4X022, Q54VS7, Q552L9, Q55E45, Q59Q36, Q5AVW1, Q5IS35, Q5NVC1, Q5PQ27, Q5XH95, Q5XHA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	43
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981158	NM_001330988.2(SLC25A25):c.1083G>C (p.Gln361His)	Pathogenic

SpliceAI

1584 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128101091:TCTA:T	acceptor_loss	1.0000
9:128101092:CTA:C	acceptor_loss	1.0000
9:128101093:TAGAA:T	acceptor_loss	1.0000
9:128101094:A:AG	acceptor_gain	1.0000
9:128101094:AGAAA:A	acceptor_loss	1.0000
9:128101095:G:GT	acceptor_gain	1.0000
9:128101095:GA:G	acceptor_gain	1.0000
9:128101095:GAA:G	acceptor_gain	1.0000
9:128101095:GAAA:G	acceptor_gain	1.0000
9:128101095:GAAAA:G	acceptor_gain	1.0000
9:128101218:TGATG:T	donor_gain	1.0000
9:128101219:GATG:G	donor_gain	1.0000
9:128101219:GATGG:G	donor_gain	1.0000
9:128101220:ATG:A	donor_gain	1.0000
9:128101220:ATGG:A	donor_loss	1.0000
9:128101221:TG:T	donor_gain	1.0000
9:128101222:GG:G	donor_gain	1.0000
9:128101223:G:GG	donor_gain	1.0000
9:128101304:TGCA:T	acceptor_loss	1.0000
9:128101307:A:AG	acceptor_gain	1.0000
9:128101307:A:AT	acceptor_loss	1.0000
9:128101307:AG:A	acceptor_gain	1.0000
9:128101307:AGGAC:A	acceptor_gain	1.0000
9:128101308:G:GT	acceptor_gain	1.0000
9:128101308:GG:G	acceptor_gain	1.0000
9:128101308:GGA:G	acceptor_gain	1.0000
9:128101308:GGAC:G	acceptor_gain	1.0000
9:128101308:GGACG:G	acceptor_gain	1.0000
9:128101392:AAGAG:A	donor_gain	1.0000
9:128101393:AGAG:A	donor_gain	1.0000

AlphaMissense

3363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128105821:T:A	N246K	1.000
9:128105821:T:G	N246K	1.000
9:128106458:G:C	G338R	1.000
9:128107126:G:A	G391D	1.000
9:128107346:G:A	G438R	1.000
9:128107346:G:C	G438R	1.000
9:128107347:G:A	G438E	1.000
9:128107360:C:A	N442K	1.000
9:128107360:C:G	N442K	1.000
9:128107385:A:C	S451R	1.000
9:128107387:C:A	S451R	1.000
9:128107387:C:G	S451R	1.000
9:128103763:T:C	L190P	0.999
9:128103772:G:A	G193E	0.999
9:128103775:G:A	G194D	0.999
9:128103781:C:A	A196E	0.999
9:128103796:G:C	R201T	0.999
9:128103797:A:C	R201S	0.999
9:128103797:A:T	R201S	0.999
9:128103808:C:A	A205D	0.999
9:128103811:C:A	P206H	0.999
9:128103816:G:C	D208H	0.999
9:128103820:G:T	R209M	0.999
9:128103823:T:C	L210P	0.999
9:128103827:G:C	K211N	0.999
9:128103827:G:T	K211N	0.999
9:128103839:G:C	Q215H	0.999
9:128103839:G:T	Q215H	0.999
9:128105810:T:A	W243R	0.999
9:128105810:T:C	W243R	0.999

dbSNP variants (sampled 300 via entrez): RS1000029633 (9:128075870 A>G), RS1000057772 (9:128093765 G>A), RS1000158578 (9:128104412 C>G,T), RS1000191648 (9:128068882 C>A), RS1000283826 (9:128087459 G>A), RS1000291442 (9:128087260 T>C), RS1000396703 (9:128079935 C>G), RS1000447532 (9:128100062 C>T), RS1000466970 (9:128080255 A>C,T), RS1000471322 (9:128075673 C>G), RS1000522010 (9:128074394 C>T), RS1000524360 (9:128074027 C>G), RS1000529105 (9:128071018 T>C), RS1000564476 (9:128070673 C>T), RS1000685745 (9:128109218 C>G)

Disease associations

OMIM: gene MIM:608745 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): nephrolithiasis (MONDO:0008171)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_65	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053040	Nephrolithiasis	C12.050.351.968.419.600; C12.050.351.968.967.249; C12.200.777.419.600; C12.200.777.967.249; C12.950.419.600; C12.950.967.249

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cisplatin	affects cotreatment, decreases expression, affects expression, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression, decreases methylation	3
Leflunomide	increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, affects methylation	2
Formaldehyde	increases expression	2
Nickel	increases expression	2
Cyclosporine	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
teriflunomide	increases expression	1
perfluorobutanesulfonic acid	decreases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4JL	HCT116-SLC25A25-KO-c11	Cancer cell line	Male
CVCL_TM26	HAP1 SLC25A25 (-) 1	Cancer cell line	Male
CVCL_TM27	HAP1 SLC25A25 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00765128	PHASE4	COMPLETED	Intravenous Ketorolac for Postoperative Pain in Percutaneous Nephrolithotomy
NCT01295879	PHASE4	COMPLETED	Vitamin D Repletion in Stone Formers With Hypercalciuria
NCT01329042	PHASE4	COMPLETED	Efficacy of Potassium Sodium Hydrogen Citrate Therapy on Renal Stone Recurrence and/or Residual Fragments After Shockwave Lithotripsy and Percutaneous Nephrolithotomy in Calcium Oxalate Urolithiasis
NCT01452880	PHASE4	COMPLETED	Remifentanil in Extracorporeal Shock Wave Lithotripsy
NCT01675362	PHASE4	COMPLETED	Are There Protective Effects of Antioxidants, Calcium Channel Blocker and Angiotensin Receptor Blocker Against Extracorporeal Shockwaves Lithotripsy Induced Renal Injury?
NCT02011737	PHASE4	UNKNOWN	Naftopidil 75mg for Improving Clearance of Urinary Stones
NCT02095665	PHASE4	COMPLETED	Ureteral Stent-related Pain and Mirabegron (SPAM) Trial
NCT02375295	PHASE4	UNKNOWN	Struvite Stones Antibiotic Study
NCT02384200	PHASE4	COMPLETED	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])
NCT02430168	PHASE4	UNKNOWN	Comparison of RIRS Versus PCNL Methods, According to Postoperative Pain and Analgesic Demand in 2 to 4 cm Renal Stones
NCT02430883	PHASE4	UNKNOWN	Is There Any Relation Between Pain and Stone Location in Retrograde Intrarenal Surgery?
NCT02443909	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w and 30w Holmium Laser Device in Management of 2-3 cm Diameter Kidney Stones With Retrograde Intrarenal Surgery
NCT02451319	PHASE4	UNKNOWN	Comparison of Safety and Efficiency of 20w 30w Holmium Laser Device in Treatment of 1-2 cm Diameter Kidney Stones With RIRS
NCT02489656	PHASE4	UNKNOWN	Quality of Life in Patients With Double Loop Ureteral Stent (JJ Silicone Hydrogel Study)
NCT02818140	PHASE4	COMPLETED	Ultrasound-guided Transmuscular Quadratus Lumborum Block for Percutaneous Nephrolithotomy
NCT02966236	PHASE4	UNKNOWN	Impact of Tranexamic Acid Use in Percutaneous Nephrolithotomy
NCT03035812	PHASE4	COMPLETED	Alkalinization by Urologists & Nephrologists
NCT03229889	PHASE4	COMPLETED	Trial of Tadalafil, Tamsulosin and Combination for Access Sheath Deployment
NCT03332056	PHASE4	COMPLETED	The Use of Belladonna and Opium Suppository in the Treatment of Postoperative Stent Pain
NCT03549611	PHASE4	WITHDRAWN	Pre-induction Analgesia: Multimodel Regimen vs Aceteminophen for Post Ureteroscopy Pain
NCT03692715	PHASE4	COMPLETED	Antibiotic Prophylaxis Before Shock Wave Lithotripsy
NCT03872843	PHASE4	COMPLETED	Opioid Free Management After Ureteroscopy
NCT03888144	PHASE4	COMPLETED	Study of Ketorolac Versus Opioid for Pain After Endoscopy
NCT04095975	PHASE4	COMPLETED	Effectiveness of Urinary Alkalinizing Agents on Kidney Stone Risk
NCT04663269	PHASE4	TERMINATED	Regional Erector Spinae Analgesic Block vs Standard of Care Undergoing Percutaneous Nephrolithotomy
NCT05082142	PHASE4	COMPLETED	Tranexamic Acid to Improve Same-day Discharge Rates After Holmium Laser Enucleation of the Prostate (HoLEP)
NCT05365477	PHASE4	COMPLETED	Empiric Versus Selective Prevention Strategies for Kidney Stone Disease
NCT05414669	PHASE4	COMPLETED	Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL
NCT05924165	PHASE4	COMPLETED	Narcotic-Free Percutaneous Nephrolithotomy
NCT06124066	PHASE4	COMPLETED	THE EFFECTS OF MIRABEGRON AND TAMSULOSIN FOR PATIENTS WITH URETERAL STENTS
NCT06966635	PHASE4	RECRUITING	Exploratory Study on the Treatment of Gout With Potassium Citrate Sustained-release Tablets
NCT07124299	PHASE4	RECRUITING	Alpha-Blockers Prior to Ureteral Access Sheath Placement in Flexible Ureteroscopy: A Randomized Prospective Study
NCT07225764	PHASE4	RECRUITING	CaOx Stone Prevention
NCT07512297	PHASE4	NOT_YET_RECRUITING	Pain Control During ESWL Using Non-Opioid Analgesics
NCT07582341	PHASE4	COMPLETED	Combined Intravenous and Irrigation Tranexamic Acid During Percutaneous Nephrolithotomy
NCT00004284	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Potassium Phosphate Vs Potassium Citrate for Absorptive Hypercalciuria
NCT00177086	PHASE3	COMPLETED	Alfuzosin Hydrochloride to Promote Passage of Distal Ureteral Calculi
NCT00713739	PHASE3	UNKNOWN	Alfuzosin for Medical Expulsion Therapy of Ureteral Stones
NCT00784472	PHASE3	COMPLETED	Visceral Pain From the Upper Urinary Tract - a Trial on the Effect of Morphine and Oxycodone in Patients Undergoing PCNL
NCT00959153	PHASE3	UNKNOWN	Extracorporeal Shock Wave Lithotriptor Indicated for Fragmenting Urinary Stones in the Kidney