SLC25A11

Summary

SLC25A11 (solute carrier family 25 member 11, HGNC:10981) is a protein-coding gene on chromosome 17p13.2, encoding Mitochondrial 2-oxoglutarate/malate carrier protein (Q02978). Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate.

The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).

Source: NCBI Gene 8402 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 91 total — 5 pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• MANE Select transcript: NM_003562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10981
Approved symbol	SLC25A11
Name	solute carrier family 25 member 11
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	OGC
Ensembl gene	ENSG00000108528
Ensembl biotype	protein_coding
OMIM	604165
Entrez	8402

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000225665, ENST00000544061, ENST00000570543, ENST00000574710, ENST00000576951, ENST00000868914, ENST00000868915, ENST00000868916, ENST00000868917, ENST00000868918, ENST00000940187

RefSeq mRNA: 3 — MANE Select: NM_003562 NM_001165417, NM_001165418, NM_003562

CCDS: CCDS11059, CCDS54069

Canonical transcript exons

ENST00000225665 — 8 exons

Exon	Start	End
ENSE00000887080	4938769	4938975
ENSE00000887081	4939060	4939212
ENSE00001313839	4937130	4937896
ENSE00002647043	4939816	4940046
ENSE00003479026	4938512	4938602
ENSE00003555056	4938339	4938429
ENSE00003606454	4938154	4938253
ENSE00003625978	4938023	4938074

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.7720 / max 223.1221, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163972	21.1668	1798
163974	15.7601	1813
163973	0.8451	544

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.01	gold quality
right atrium auricular region	UBERON:0006631	97.97	gold quality
heart left ventricle	UBERON:0002084	97.83	gold quality
cardiac ventricle	UBERON:0002082	97.74	gold quality
cardiac atrium	UBERON:0002081	97.73	gold quality
gastrocnemius	UBERON:0001388	97.69	gold quality
muscle of leg	UBERON:0001383	97.08	gold quality
body of tongue	UBERON:0011876	96.92	gold quality
heart	UBERON:0000948	96.80	gold quality
muscle organ	UBERON:0001630	96.66	gold quality
skeletal muscle organ	UBERON:0014892	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.52	gold quality
right frontal lobe	UBERON:0002810	96.02	gold quality
prefrontal cortex	UBERON:0000451	95.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.87	gold quality
metanephros cortex	UBERON:0010533	95.73	gold quality
skeletal muscle tissue	UBERON:0001134	95.72	gold quality
diaphragm	UBERON:0001103	95.71	gold quality
vastus lateralis	UBERON:0001379	95.55	gold quality
quadriceps femoris	UBERON:0001377	95.45	gold quality
muscle tissue	UBERON:0002385	95.38	gold quality
biceps brachii	UBERON:0001507	95.21	gold quality
cingulate cortex	UBERON:0003027	94.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.94	gold quality
right adrenal gland	UBERON:0001233	94.92	gold quality
anterior cingulate cortex	UBERON:0009835	94.91	gold quality
triceps brachii	UBERON:0001509	94.86	gold quality
right adrenal gland cortex	UBERON:0035827	94.86	gold quality
left adrenal gland	UBERON:0001234	94.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

21 targeting SLC25A11, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6076	98.61	65.69	637
HSA-MIR-7976	95.75	65.67	1186

Literature-anchored findings (GeneRIF, showing 9)

• data provide evidence for a role of the 2-oxoglutarate carrier as a glutathione transporting polypeptide (PMID:12939596)
• porphyrin accumulation in mitochondria is mediated by OGC and porphyrins are able to competitively inhibit 2-oxoglutarate uptake into mitochondria (PMID:16920706)
• Controlling MISC-1/OGC function allows regulation of mitochondrial morphology and cell survival decisions by the metabolic needs of the cell. (PMID:21448454)
• OGCP degrades through proteasome and lysosome degradation pathways. The degradation of parkin protein can promote the degradation of OGCP. (PMID:21500544)
• OGC as a model protein for understanding the transport mechanism of mitochondrial carriers. (PMID:23054077)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• The Network analyses identified SLC25A11expression in temporal cortex in patient with late-onset Alzheimer’s disease. (PMID:28242297)
• data show that SLC25A11 is a novel paraganglioma susceptibility gene for which loss of function correlates with metastatic presentation (PMID:29431636)
• Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production (PMID:30686754)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a11	ENSDARG00000035741
mus_musculus	Slc25a11	ENSMUSG00000014606
rattus_norvegicus	Slc25a11	ENSRNOG00000003815
drosophila_melanogaster	CG7514	FBGN0035567
drosophila_melanogaster	CG18418	FBGN0035568
drosophila_melanogaster	CG1907	FBGN0039674
caenorhabditis_elegans		WBGENE00015186

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), 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 2-oxoglutarate/malate carrier protein — Q02978 (reviewed: Q02978)

Alternative names: Solute carrier family 25 member 11

All UniProt accessions (3): Q02978, I3L1P8, Q6IBH0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate. Can also exchange 2-oxoglutarate for other dicarboxylic acids such as malonate, succinate, maleate and oxaloacetate, although with lower affinity. Substrate exchange across the membrane occurs consecutively with one substrate being transported first, then dissociating from the substrate binding site before the second substrate binds for transport in the opposite direction. Does not transport glutathione. Contributes to several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, gluconeogenesis from lactate, and nitrogen metabolism. Maintains mitochondrial fusion and fission events, and the organization and morphology of cristae. Involved in the regulation of apoptosis.

Subunit / interactions. Monomer. Interacts with SMIM26.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Most highly expressed in the heart.

Disease relevance. Pheochromocytoma/paraganglioma syndrome 6 (PPGL6) [MIM:618464] A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL6 inheritance is autosomal dominant. Disease susceptibility is associated with variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q02978-1	1	yes
Q02978-2	2

RefSeq proteins (3): NP_001158889, NP_001158890, NP_003553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR050391	Mito_Metabolite_Transporter	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 5 shown:

• (S)-malate(in) + 2-oxoglutarate(out) = (S)-malate(out) + 2-oxoglutarate(in) (RHEA:71587)
• malonate(in) + 2-oxoglutarate(out) = malonate(out) + 2-oxoglutarate(in) (RHEA:71591)
• succinate(in) + 2-oxoglutarate(out) = succinate(out) + 2-oxoglutarate(in) (RHEA:71595)
• maleate(in) + 2-oxoglutarate(out) = maleate(out) + 2-oxoglutarate(in) (RHEA:71599)
• oxaloacetate(in) + 2-oxoglutarate(out) = oxaloacetate(out) + 2-oxoglutarate(in) (RHEA:71603)

UniProt features (22 total): modified residue 6, transmembrane region 6, repeat 3, sequence variant 3, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02978-F1	87.54	0.58

Functional residue map

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

Post-translational modifications (6): 2, 6, 57, 73, 102, 256

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-428643	Organic anion transport by SLC5/17/25 transporters
R-HSA-9856872	Malate-aspartate shuttle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-611105	Respiratory electron transport

MSigDB gene sets: 318 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_ATRX, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MORF_PPP5C, MORF_FANCG, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_DICARBOXYLIC_ACID_TRANSPORT

GO Biological Process (6): gluconeogenesis (GO:0006094), lipid transport (GO:0006869), malate-aspartate shuttle (GO:0043490), alpha-ketoglutarate transport (GO:0015742), transmembrane transport (GO:0055085), malate transmembrane transport (GO:0071423)

GO Molecular Function (6): RNA binding (GO:0003723), oxoglutarate:malate antiporter activity (GO:0015367), transmembrane transporter activity (GO:0022857), protein binding (GO:0005515), alpha-ketoglutarate transmembrane transporter activity (GO:0015139), antiporter activity (GO:0015297)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transport of organic anions	1
Respiratory electron transport	1
Metabolism	1
Transport of small molecules	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
intracellular membrane-bounded organelle	2
glucose metabolic process	1
hexose biosynthetic process	1
lipid localization	1
L-aspartate:2-oxoglutarate transaminase activity	1
NAD+ metabolic process	1
L-malate dehydrogenase (NAD+) activity	1
mitochondrial transmembrane transport	1
dicarboxylic acid transport	1
cellular process	1
malate transport	1
carboxylic acid transmembrane transport	1
nucleic acid binding	1
alpha-ketoglutarate transmembrane transporter activity	1
malate transmembrane transporter activity	1
antiporter activity	1
transporter activity	1
transmembrane transport	1
binding	1
dicarboxylic acid transmembrane transporter activity	1
alpha-ketoglutarate transport	1
secondary active transmembrane transporter activity	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A11	MDH2	P40926	771
SLC25A11	MTCH1	Q9NZJ7	750
SLC25A11	MTCH2	Q9Y6C9	693
SLC25A11	TMEM127	O75204	581
SLC25A11	PDHB	P11177	539
SLC25A11	SLC25A13	Q9UJS0	536
SLC25A11	SLC25A12	O75746	503
SLC25A11	HRAS	P01112	498
SLC25A11	F5H5T6	F5H5T6	480
SLC25A11	SDHA	P31040	476
SLC25A11	IDH2	P48735	476
SLC25A11	SDHAF2	Q9NX18	476
SLC25A11	IDH3G	P51553	472
SLC25A11	SDHD	O14521	471
SLC25A11	PKM	P14618	471

IntAct

192 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AGK	SMIM26	psi-mi:“MI:0914”(association)	0.650
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
SMIM26	SLC25A11	psi-mi:“MI:0915”(physical association)	0.630
SMIM26	SLC25A11	psi-mi:“MI:0403”(colocalization)	0.630
SLC25A11	SMIM26	psi-mi:“MI:0915”(physical association)	0.630
SMIM26	SLC25A11	psi-mi:“MI:0914”(association)	0.630
CALR	SLC25A11	psi-mi:“MI:0915”(physical association)	0.560
SLC25A11	CDH1	psi-mi:“MI:0915”(physical association)	0.560
SLC25A11	DLST	psi-mi:“MI:0915”(physical association)	0.560
SLC25A11		psi-mi:“MI:0915”(physical association)	0.560
CDK5R1	SLC25A11	psi-mi:“MI:0915”(physical association)	0.560
SLC25A11	AHCYL1	psi-mi:“MI:0915”(physical association)	0.560
SLC25A11	NEK7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (324): SLC25A11 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), SLC25A11 (Affinity Capture-MS), POTEI (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), FYN (Affinity Capture-MS), YES1 (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS), UPF3B (Affinity Capture-MS), SMAP2 (Affinity Capture-MS), PRKCA (Affinity Capture-MS), ZNF703 (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: A0A0G2K5L2, A2ADF7, A4QNX2, B0G143, F1LX07, F1LZW6, F1RFX9, O13844, O43772, O75746, P16261, P39953, Q02978, Q08DK4, Q0II44, Q12482, Q1DRJ3, Q21153, Q26365, Q3KQZ1, Q3TZX3, Q4V8K4, Q505J6, Q54QN2, Q54RB9, Q552L9, Q58DS3, Q5B717, Q5RBC8, Q5RD81, Q5SWT3, Q5XIF9, Q5ZKP7, Q66L49, Q68F18, Q6ZT89, Q75AH6, Q7PQV7, Q86AV5, Q8BH59

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
FCERI mediated MAPK activation	7	19.1×	3e-05
RAF activation	5	13.2×	3e-03
Signaling by high-kinase activity BRAF mutants	5	12.5×	3e-03
MAP2K and MAPK activation	5	11.2×	5e-03
Signaling by RAF1 mutants	5	11.0×	5e-03
MAPK6/MAPK4 signaling	10	10.7×	3e-05
Negative regulation of MAPK pathway	5	10.5×	5e-03
Defective CFTR causes cystic fibrosis	6	10.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	8	8.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	44
Likely benign	32
Benign	3

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
635126	NM_003562.5(SLC25A11):c.715C>A (p.Pro239Thr)	Pathogenic
635127	NM_003562.5(SLC25A11):c.439A>G (p.Met147Val)	Pathogenic
635128	NM_003562.5(SLC25A11):c.708C>T (p.Ala236=)	Pathogenic
635129	NM_003562.5(SLC25A11):c.421G>A (p.Glu141Lys)	Pathogenic
635130	NM_003562.5(SLC25A11):c.107_108del (p.Thr36fs)	Pathogenic

SpliceAI

941 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4937893:CGTC:C	acceptor_gain	1.0000
17:4937894:GTCC:G	acceptor_loss	1.0000
17:4937896:CCTA:C	acceptor_loss	1.0000
17:4937897:C:CC	acceptor_gain	1.0000
17:4938016:T:TA	donor_gain	1.0000
17:4938017:CCTCA:C	donor_loss	1.0000
17:4938018:CTCA:C	donor_loss	1.0000
17:4938019:TCAC:T	donor_loss	1.0000
17:4938020:CACCA:C	donor_loss	1.0000
17:4938021:A:AC	donor_gain	1.0000
17:4938022:C:CA	donor_loss	1.0000
17:4938022:C:CC	donor_gain	1.0000
17:4938022:CCAG:C	donor_gain	1.0000
17:4938070:GGATT:G	acceptor_gain	1.0000
17:4938071:GATT:G	acceptor_gain	1.0000
17:4938072:ATT:A	acceptor_gain	1.0000
17:4938073:TT:T	acceptor_gain	1.0000
17:4938074:TC:T	acceptor_loss	1.0000
17:4938075:C:CC	acceptor_gain	1.0000
17:4938075:CTG:C	acceptor_loss	1.0000
17:4938150:TCAC:T	donor_loss	1.0000
17:4938151:CACC:C	donor_loss	1.0000
17:4938152:A:AC	donor_gain	1.0000
17:4938152:AC:A	donor_gain	1.0000
17:4938152:ACCG:A	donor_loss	1.0000
17:4938153:C:CC	donor_gain	1.0000
17:4938153:CC:C	donor_gain	1.0000
17:4938153:CCG:C	donor_gain	1.0000
17:4938153:CCGG:C	donor_gain	1.0000
17:4938153:CCGGG:C	donor_gain	1.0000

AlphaMissense

2021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4937845:C:G	G281R	1.000
17:4938213:G:C	S226R	1.000
17:4938213:G:T	S226R	1.000
17:4938215:T:G	S226R	1.000
17:4938358:C:A	K206N	1.000
17:4938358:C:G	K206N	1.000
17:4939170:C:A	K46N	1.000
17:4939170:C:G	K46N	1.000
17:4937784:T:A	E301V	0.999
17:4937796:A:G	F297S	0.999
17:4937805:A:T	V294D	0.999
17:4937817:C:T	G290D	0.999
17:4937851:A:G	W279R	0.999
17:4937851:A:T	W279R	0.999
17:4938068:C:A	Q248H	0.999
17:4938068:C:G	Q248H	0.999
17:4938154:C:G	R246P	0.999
17:4938159:C:A	K244N	0.999
17:4938159:C:G	K244N	0.999
17:4938169:T:A	D241V	0.999
17:4938169:T:C	D241G	0.999
17:4938169:T:G	D241A	0.999
17:4938170:C:G	D241H	0.999
17:4938170:C:T	D241N	0.999
17:4938175:G:T	P239H	0.999
17:4938202:C:T	G230D	0.999
17:4938203:C:G	G230R	0.999
17:4938204:G:C	S229R	0.999
17:4938204:G:T	S229R	0.999
17:4938205:C:A	S229I	0.999

dbSNP variants (sampled 300 via entrez): RS1000580299 (17:4937142 T>C,G), RS1001333628 (17:4939520 C>T), RS1001935294 (17:4940684 A>G), RS1002984190 (17:4941730 A>G), RS1003134444 (17:4937351 G>A,C,T), RS1003475157 (17:4938766 C>T), RS1004075859 (17:4941872 G>T), RS1004252813 (17:4937255 C>T), RS1005165997 (17:4938556 G>A), RS1006114998 (17:4940369 A>G), RS1007170943 (17:4941446 C>T), RS1007416364 (17:4939576 C>A), RS1007529796 (17:4941640 C>T), RS1007695549 (17:4936964 G>A), RS1007733800 (17:4939308 T>C)

Disease associations

OMIM: gene MIM:604165 | disease phenotypes: MIM:618464

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary pheochromocytoma-paraganglioma	Supportive	Autosomal dominant
pheochromocytoma/paraganglioma syndrome 6	Limited	Autosomal dominant

Mondo (2): pheochromocytoma/paraganglioma syndrome 6 (MONDO:0032767), hereditary pheochromocytoma-paraganglioma (MONDO:0017366)

Orphanet (0):

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000405	Conductive hearing impairment
HP:0000526	Aniridia
HP:0000740	Episodic paroxysmal anxiety
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000980	Pallor
HP:0001069	Episodic hyperhidrosis
HP:0001095	Hypertensive retinopathy
HP:0001293	Cranial nerve compression
HP:0001337	Tremor
HP:0001342	Cerebral hemorrhage
HP:0001605	Vocal cord paralysis
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001824	Weight loss
HP:0001962	Palpitations
HP:0002018	Nausea
HP:0002331	Recurrent paroxysmal headache
HP:0002574	Episodic abdominal pain
HP:0002640	Hypertension associated with pheochromocytoma
HP:0002668	Paraganglioma
HP:0002864	Paraganglioma of head and neck
HP:0003072	Hypercalcemia
HP:0003334	Elevated circulating catecholamine level
HP:0003345	Elevated urinary norepinephrine level
HP:0003528	Elevated circulating calcitonin concentration
HP:0003574	Positive regitine blocking test

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004603_173	Platelet count	1.000000e-19
GCST004607_69	Plateletcrit	1.000000e-12
GCST004616_75	Platelet distribution width	2.000000e-26
GCST90002401_577	Platelet distribution width	8.000000e-81

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067210 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Mitochondrial di- and tri-carboxylic acid transporter subfamily

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Kd	1.986	nM	CHEMBL5653589
8.70	ED50	1.986	nM	CHEMBL5653589
7.28	Kd	53.14	nM	CHEMBL3752910
7.28	ED50	53.14	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149406: Binding affinity to human SLC25A11 incubated for 45 mins by Kinobead based pull down assay	kd	0.0020	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149406: Binding affinity to human SLC25A11 incubated for 45 mins by Kinobead based pull down assay	kd	0.0531	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
cobaltous chloride	decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases expression, increases abundance	1
Cisplatin	increases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Environmental Pollutants	affects expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652448	Binding	Binding affinity to human SLC25A11 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4PB	HEK293T SLC25A11 KO	Transformed cell line	Female
CVCL_D4JD	HCT116-SLC25A11-KO-c16	Cancer cell line	Male
CVCL_TM08	HAP1 SLC25A11 (-) 1	Cancer cell line	Male
CVCL_TM09	HAP1 SLC25A11 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition