SLC25A6

Summary

SLC25A6 (solute carrier family 25 member 6, HGNC:10992) is a protein-coding gene on chromosome Xp22.32 and Yp11.3, encoding ADP/ATP translocase 3 (P12236). ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell.

This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein is implicated in the function of the permability transition pore complex (PTPC), which regulates the release of mitochondrial products that induce apoptosis. The human genome contains several non-transcribed pseudogenes of this gene.

Source: NCBI Gene 293 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001636

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10992
Approved symbol	SLC25A6
Name	solute carrier family 25 member 6
Location	Xp22.32 and Yp11.3
Locus type	gene with protein product
Status	Approved
Aliases	ANT3Y, MGC17525
Ensembl gene	ENSG00000169100
Ensembl biotype	protein_coding
OMIM	300151, 403000
Entrez	293

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000381401, ENST00000475167, ENST00000484026, ENST00000871942, ENST00000871943, ENST00000871944, ENST00000936562, ENST00000936563, ENST00000936564, ENST00000936565, ENST00000936566, ENST00000966894, ENST00000966895

RefSeq mRNA: 1 — MANE Select: NM_001636 NM_001636

CCDS: CCDS14114

Canonical transcript exons

ENST00000381401 — 4 exons

Exon	Start	End
ENSE00001153206	1386152	1386759
ENSE00001801425	1387279	1387419
ENSE00001913454	1391899	1392113
ENSE00003590251	1389241	1389727

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.70	gold quality
renal medulla	UBERON:0000362	99.66	gold quality
nipple	UBERON:0002030	99.59	gold quality
left ovary	UBERON:0002119	99.58	gold quality
embryo	UBERON:0000922	99.57	gold quality
pylorus	UBERON:0001166	99.56	gold quality
mammalian vulva	UBERON:0000997	99.55	gold quality
body of stomach	UBERON:0001161	99.54	gold quality
right ovary	UBERON:0002118	99.53	gold quality
ganglionic eminence	UBERON:0004023	99.53	gold quality
right lobe of thyroid gland	UBERON:0001119	99.52	gold quality
metanephros cortex	UBERON:0010533	99.52	gold quality
left adrenal gland	UBERON:0001234	99.51	gold quality
adenohypophysis	UBERON:0002196	99.51	gold quality
type B pancreatic cell	CL:0000169	99.50	gold quality
penis	UBERON:0000989	99.50	gold quality
left lobe of thyroid gland	UBERON:0001120	99.50	gold quality
body of pancreas	UBERON:0001150	99.50	gold quality
right adrenal gland	UBERON:0001233	99.50	gold quality
adrenal cortex	UBERON:0001235	99.50	gold quality
lower esophagus	UBERON:0013473	99.50	gold quality
left adrenal gland cortex	UBERON:0035825	99.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.50	gold quality
fundus of stomach	UBERON:0001160	99.48	gold quality
cervix squamous epithelium	UBERON:0006922	99.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.48	gold quality
right adrenal gland cortex	UBERON:0035827	99.48	gold quality
pituitary gland	UBERON:0000007	99.47	gold quality
cardia of stomach	UBERON:0001162	99.47	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	42.52
E-HCAD-4	yes	40.84
E-MTAB-10553	yes	36.42
E-HCAD-5	yes	32.22
E-HCAD-9	yes	29.64
E-HCAD-31	yes	21.56
E-CURD-122	yes	20.87
E-GEOD-135922	yes	11.46
E-MTAB-10042	yes	10.75
E-MTAB-9067	yes	10.01
E-MTAB-6678	yes	9.14
E-CURD-88	yes	7.71
E-CURD-98	no	2206.95
E-MTAB-8205	no	1974.72
E-GEOD-125970	no	1609.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1

miRNA regulators (miRDB)

27 targeting SLC25A6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-4462	95.10	66.27	172
HSA-MIR-11400	94.03	67.12	81

Literature-anchored findings (GeneRIF, showing 13)

• Of three ANT isoforms expressed in yeast, ANC3 is the most efficient to restore yeast growth on a nonfermentable carbon source of a yeast mutant strain lacking its three endogenous ANC. (PMID:12450408)
• Results demonstrate that induction of adenine nucleotide translocase 3 by interleukin-4 and interferon-gamma proceeds via pathways involving STAT6 and STAT1, respectively. (PMID:14746803)
• ANT3 overexpression induces apoptosis in cultured cells. (PMID:15063741)
• Results revealed that ANT1 and ANT3 (adenine nucleotide translocase 1-3) over-expressing HeLa cells increased their atRA sensitivity. (PMID:16556444)
• ANT3 has a potential role in T-helper cell survival and immune cell homeostasis. (PMID:16930576)
• involvement of ANT in cell death is cell type- and stimulus-dependent (PMID:17855512)
• The dynamics of the molecular interactions between the C-terminal region of PB1-F2 protein and VDAC1 and ANT3 were expounded by employing an in silico approach. (PMID:19669810)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• Human ANT3 expression is directly downregulated by overexpression of hcmv-miR-UL36-5p. (PMID:26212361)
• cancer cells require both hANT2 and hANT3, depending on their proliferation status: hANT2 when proliferation rates are high, and hANT3 when proliferation slows. (PMID:26842067)
• Mortalin (HSPA9) facilitates BRAF-mutant tumor cell survival by suppressing ANT3-mediated mitochondrial membrane permeability. (PMID:32156782)
• Differential Expression of ADP/ATP Carriers as a Biomarker of Metabolic Remodeling and Survival in Kidney Cancers. (PMID:33396658)
• Dosage of the pseudoautosomal gene SLC25A6 is implicated in QTc interval duration. (PMID:37495650)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a6	ENSDARG00000005853

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), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

ADP/ATP translocase 3 — P12236 (reviewed: P12236)

Alternative names: ADP,ATP carrier protein 3, ADP,ATP carrier protein, isoform T2, Adenine nucleotide translocator 3, Solute carrier family 25 member 6

All UniProt accessions (2): P12236, Q6I9V5

UniProt curated annotations — full annotation on UniProt →

Function. ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell. Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane. In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity. Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis. Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A6/ANT3 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it. Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death. It is however unclear if SLC25A6/ANT3 constitutes a pore-forming component of mPTP or regulates it.

Subunit / interactions. Monomer. Found in a complex with ARL2, ARL2BP and SLC25A6/ANT3. (Microbial infection) Interacts with influenza A virus PB1-F2 protein. (Microbial infection) Interacts with HIV-1 Vpr.

Subcellular location. Mitochondrion inner membrane. Membrane.

Tissue specificity. Expressed in erythrocytes (at protein level).

Post-translational modifications. Trimethylated by ANTKMT at Lys-52.

Activity regulation. The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR). Proton transporter activity is inhibited by ADP:ATP antiporter activity.

Domain organisation. The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.

Miscellaneous. The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes and escapes X-inactivation.

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

RefSeq proteins (1): NP_001627* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002067	MCP	Family
IPR002113	ADT_euk_type	Family
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153

Catalyzed reactions (Rhea), 2 shown:

• H(+)(in) = H(+)(out) (RHEA:34979)
• ADP(in) + ATP(out) = ADP(out) + ATP(in) (RHEA:34999)

UniProt features (31 total): topological domain 7, transmembrane region 6, modified residue 5, repeat 3, binding site 3, chain 2, initiator methionine 1, region of interest 1, short sequence motif 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12236-F1	92.40	0.70

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 (3): 80; 92; 235

Post-translational modifications (5): 1, 2, 52, 105, 268

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-168277	Influenza Virus Induced Apoptosis
R-HSA-180897	Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-176033	Interactions of Vpr with host cellular proteins
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5663205	Infectious disease
R-HSA-9609507	Protein localization
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 251 (showing top): REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, XU_GH1_AUTOCRINE_TARGETS_UP, GCM_NPM1, MORF_SNRP70, MORF_UBE2I, HSIAO_HOUSEKEEPING_GENES, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, REACTOME_HIV_INFECTION, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOTIDE_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (5): apoptotic process (GO:0006915), mitochondrial ADP transmembrane transport (GO:0140021), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029), mitochondrial ATP transmembrane transport (GO:1990544), transmembrane transport (GO:0055085)

GO Molecular Function (3): ATP:ADP antiporter activity (GO:0005471), protein binding (GO:0005515), antiporter activity (GO:0015297)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM23 mitochondrial import inner membrane translocase complex (GO:0005744), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Viral Infection Pathways	2
Protein localization	1
Influenza Infection	1
Interactions of Vpr with host cellular proteins	1
Transport of vitamins, nucleosides, and related molecules	1
Metabolism of proteins	1
HIV Infection	1
Host Interactions of HIV factors	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine-containing compound transmembrane transport	2
nucleotide transmembrane transport	2
intracellular membrane-bounded organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
ADP transport	1
negative regulation of organelle organization	1
negative regulation of mitochondrial membrane permeability	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
ATP transport	1
transport	1
cellular process	1
ATP transmembrane transporter activity	1
ADP transmembrane transporter activity	1
antiporter activity	1
binding	1
secondary active transmembrane transporter activity	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2513 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A6	CIAO2B	Q9Y3D0	945
SLC25A6	CIAO1	O76071	934
SLC25A6	VDAC1	P21796	930
SLC25A6	MMS19	Q96T76	918
SLC25A6	ASMTL	O95671	885
SLC25A6	VDAC2	P45880	879
SLC25A6	ASMT	P46597	849
SLC25A6	CSF2RA	P15509	785
SLC25A6	STS	P08842	761
SLC25A6	AKAP17A	Q02040	752
SLC25A6	MFN2	O95140	721
SLC25A6	TIMM23	O14925	669
SLC25A6	EPRS1	P07814	625
SLC25A6	CD99	P14209	625
SLC25A6	SLC25A3	Q00325	601

IntAct

357 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
NDUFAF5	NDUFAF8	psi-mi:“MI:0914”(association)	0.750
LYRM2	NDUFAB1	psi-mi:“MI:0914”(association)	0.730
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
AP2B1	SLC25A6	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	SLC25A6	psi-mi:“MI:0915”(physical association)	0.670
SLC25A6	AP2B1	psi-mi:“MI:0915”(physical association)	0.670
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
LYRM4	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PB1	SLC25A6	psi-mi:“MI:0915”(physical association)	0.590
SLC25A6	PB1	psi-mi:“MI:0915”(physical association)	0.590
TRIM23	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560
KRT31	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (558): SLC25A6 (Affinity Capture-MS), SLC25A6 (Two-hybrid), TRIM23 (Two-hybrid), KRT31 (Two-hybrid), TRAF1 (Two-hybrid), TRIP6 (Two-hybrid), MID2 (Two-hybrid), MTUS2 (Two-hybrid), LZTS2 (Two-hybrid), TEKT4 (Two-hybrid), NOTCH2NL (Two-hybrid), SLC25A6 (Affinity Capture-MS), SLC25A6 (Affinity Capture-MS), LCOR (Affinity Capture-MS), SLC25A6 (Affinity Capture-MS)

ESM2 similar proteins: A6QR09, F1R4U0, F1RFX9, O43772, O46373, O77792, O95258, O97562, O97649, P02722, P05141, P12235, P12236, P22292, P32007, P32089, P48962, P51881, P53007, P55851, P70406, P79110, P97700, Q000K2, Q02978, Q05962, Q08DK4, Q09073, Q3SZI5, Q5PQM9, Q5R5A1, Q5R5A8, Q5SVS4, Q5U680, Q5XGI1, Q6GQ22, Q6QRN9, Q70HW3, Q8HXE3, Q8HXY2

Diamond homologs: A2A3V2, A2ASZ8, A2CEQ0, A5DIS9, A5PJZ1, B0G159, B4F8I5, B4FIJ0, B8ZHC9, F4HW79, F4JU70, G2QNH0, K7VYZ9, O04619, O18757, O22342, O46373, O65023, O75746, O94502, P02722, P04709, P04710, P05141, P0C546, P12235, P12236, P12857, P16260, P16261, P25083, P27081, P29518, P31167, P31691, P31692, P32007, P33303, P40941, P48962

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 209 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	8	9.5×	6e-04
Complex I biogenesis	7	8.2×	3e-03
Respiratory electron transport	12	8.0×	3e-05
Potential therapeutics for SARS	9	7.2×	9e-04
Platelet activation, signaling and aggregation	9	6.7×	1e-03
Mitochondrial protein degradation	8	6.4×	4e-03
Aerobic respiration and respiratory electron transport	10	6.2×	9e-04
Infectious disease	17	3.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	19.5×	3e-03
mitochondrial respiratory chain complex I assembly	6	13.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

852 predictions. Top by Δscore:

Variant	Effect	Δscore
X:1386755:GTCAG:G	acceptor_gain	1.0000
X:1386756:TCAG:T	acceptor_gain	1.0000
X:1386756:TCAGC:T	acceptor_loss	1.0000
X:1386757:CAG:C	acceptor_gain	1.0000
X:1386757:CAGC:C	acceptor_gain	1.0000
X:1386757:CAGCT:C	acceptor_loss	1.0000
X:1386758:AG:A	acceptor_gain	1.0000
X:1386759:GC:G	acceptor_loss	1.0000
X:1386760:C:CC	acceptor_gain	1.0000
X:1386761:T:A	acceptor_loss	1.0000
X:1387277:ACCT:A	donor_gain	1.0000
X:1387278:C:CG	donor_loss	1.0000
X:1387278:CCTC:C	donor_gain	1.0000
X:1387280:T:TA	donor_gain	1.0000
X:1387281:C:A	donor_gain	1.0000
X:1389239:AC:A	donor_gain	1.0000
X:1389240:CC:C	donor_gain	1.0000
X:1387420:C:CC	acceptor_gain	0.9900
X:1389235:ACGT:A	donor_loss	0.9900
X:1389236:CGTA:C	donor_loss	0.9900
X:1389237:GTACC:G	donor_loss	0.9900
X:1389238:T:TG	donor_loss	0.9900
X:1389239:A:AC	donor_gain	0.9900
X:1389240:C:A	donor_loss	0.9900
X:1389240:C:CC	donor_gain	0.9900
X:1389724:GGAC:G	acceptor_loss	0.9900
X:1389724:GGACC:G	acceptor_gain	0.9900
X:1389726:ACCT:A	acceptor_gain	0.9900
X:1389726:ACCTG:A	acceptor_loss	0.9900
X:1389728:CTGG:C	acceptor_loss	0.9900

AlphaMissense

3886 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:1386636:A:T	L288Q	1.000
Y:1386651:C:T	G283E	1.000
Y:1386652:C:G	G283R	1.000
Y:1386652:C:T	G283R	1.000
Y:1386682:C:A	G273C	1.000
Y:1386682:C:G	G273R	1.000
Y:1386728:A:C	C257W	1.000
Y:1386729:C:T	C257Y	1.000
Y:1387323:T:A	D232V	1.000
Y:1387324:C:G	D232H	1.000
Y:1387345:C:G	G225R	1.000
Y:1387347:G:T	A224D	1.000
Y:1387378:A:G	W214R	1.000
Y:1387378:A:T	W214R	1.000
Y:1389252:T:A	D196V	1.000
Y:1389261:C:T	G193D	1.000
Y:1389262:C:G	G193R	1.000
Y:1389263:G:C	F192L	1.000
Y:1389263:G:T	F192L	1.000
Y:1389264:A:C	F192C	1.000
Y:1389264:A:G	F192S	1.000
Y:1389265:A:G	F192L	1.000
Y:1389273:G:T	A189E	1.000
Y:1389276:C:G	R188P	1.000
Y:1389292:C:G	G183R	1.000
Y:1389312:C:T	G176D	1.000
Y:1389313:C:A	G176C	1.000
Y:1389313:C:G	G176R	1.000
Y:1389377:G:C	F154L	1.000
Y:1389377:G:T	F154L	1.000

dbSNP variants (sampled 300 via entrez): RS1055341021 (X:1386652 C>A), RS111324409 (X:1391690 G>A,C), RS111338474 (X:1388330 G>A,C), RS11211819 (X:1386577 G>A,C,T), RS112264344 (X:1390908 G>A,T), RS112368626 (X:1387057 C>T), RS112727268 (X:1388723 A>G,T), RS112908894 (X:1390858 G>A), RS113070225 (X:1388351 G>A), RS113412992 (X:1391140 A>AT), RS113518265 (X:1393526 C>G,T), RS113543169 (X:1393044 T>A,G), RS1135434 (X:1389640 C>A,G,T), RS113634215 (X:1386568 GGTGTGTGT>G,GGT,GGTGT,GGTGTGT,GGTGTGTGTGT,GGTGTGTGTGTGT,GGTGTGTGTGTGTGT,GGTGTGTGTGTGTGTGT), RS113659794 (X:1391152 G>A)

Disease associations

OMIM: gene MIM:300151, MIM:403000 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105854 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,741 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	Kd	6	nM	MASITINIB
6.91	Kd	121.9	nM	CHEMBL5653589
6.91	ED50	121.9	nM	CHEMBL5653589
6.54	IC50	290	nM	MOLIBRESIB
6.30	Kd	495	nM	GILTERITINIB
5.66	Kd	2188	nM	CHEMBL3752910
5.66	Kd	2193	nM	CHEMBL3752910
5.66	ED50	2193	nM	CHEMBL3752910

PubChem BioAssay actives

6 with measured affinity, of 250 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	1425170: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149412: Binding affinity to human SLC25A6 incubated for 45 mins by Kinobead based pull down assay	kd	0.1219	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178700: Inhibition of SLC25A6 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2900	uM
Gilteritinib	1425170: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4950	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149412: Binding affinity to human SLC25A6 incubated for 45 mins by Kinobead based pull down assay	kd	2.1878	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
Tretinoin	increases response to substance, affects cotreatment, increases expression, decreases expression	3
sodium arsenite	affects cotreatment, increases expression	2
CD 437	decreases expression, decreases activity	2
Rotenone	increases expression	2
aristolochic acid I	decreases expression	1
dehydroabietylamine	affects activity	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
closantel	decreases activity	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	increases expression	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	increases expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991883	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4D1	HCT116-SLC25A6-KO-c4	Cancer cell line	Male
CVCL_D4D2	HCT116-SLC25A6-KO-c8	Cancer cell line	Male
CVCL_D8V9	Ubigene HCT 116 SLC25A6 KO	Cancer cell line	Male
CVCL_E0NQ	Ubigene HeLa SLC25A6 KO	Cancer cell line	Female
CVCL_E2K6	HAP1 SLC25A6 (-) 2	Cancer cell line	Male
CVCL_TM58	HAP1 SLC25A6 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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