SLC25A26

Summary

SLC25A26 (solute carrier family 25 member 26, HGNC:20661) is a protein-coding gene on chromosome 3p14.1, encoding Mitochondrial S-adenosylmethionine carrier protein (Q70HW3). Mitochondrial S-adenosyl-L-methionine/S-adenosyl-L-homocysteine antiporter. It is a selective cancer dependency (DepMap: 41.9% of cell lines).

This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 115286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 201 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 19
• Cancer dependency (DepMap): dependent in 41.9% of screened cell lines
• MANE Select transcript: NM_001379210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20661
Approved symbol	SLC25A26
Name	solute carrier family 25 member 26
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	SAMC
Ensembl gene	ENSG00000144741
Ensembl biotype	protein_coding
OMIM	611037
Entrez	115286

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 10 protein_coding, 9 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000336733, ENST00000354883, ENST00000413054, ENST00000464350, ENST00000483224, ENST00000484768, ENST00000676754, ENST00000685460, ENST00000686445, ENST00000686511, ENST00000687663, ENST00000688696, ENST00000689520, ENST00000690522, ENST00000690560, ENST00000690634, ENST00000691166, ENST00000691461, ENST00000691525, ENST00000691582, ENST00000691603, ENST00000693385, ENST00000895732, ENST00000895733, ENST00000895734

RefSeq mRNA: 9 — MANE Select: NM_001379210 NM_001164796, NM_001350993, NM_001379210, NM_001400705, NM_001400707, NM_001400709, NM_001400711, NM_001400714, NM_173471

CCDS: CCDS2905, CCDS54604, CCDS93306, CCDS93307

Canonical transcript exons

ENST00000354883 — 10 exons

Exon	Start	End
ENSE00001736489	66236544	66236700
ENSE00003468034	66369478	66369542
ENSE00003508045	66370529	66370602
ENSE00003561141	66263332	66263379
ENSE00003563940	66362860	66362929
ENSE00003596181	66346364	66346408
ENSE00003615998	66262051	66262155
ENSE00003687644	66377690	66378923
ENSE00003704267	66243203	66243312
ENSE00003909199	66221001	66221127

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0989 / max 146.8102, expressed in 1803 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37188	13.6102	1796
37189	1.4239	932
37190	0.6092	335
37187	0.4556	210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	92.60	gold quality
muscle of leg	UBERON:0001383	92.40	gold quality
apex of heart	UBERON:0002098	91.84	gold quality
prefrontal cortex	UBERON:0000451	90.97	gold quality
skeletal muscle tissue	UBERON:0001134	90.83	gold quality
heart left ventricle	UBERON:0002084	90.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.70	gold quality
frontal cortex	UBERON:0001870	90.14	gold quality
anterior cingulate cortex	UBERON:0009835	89.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.67	gold quality
cerebral cortex	UBERON:0000956	89.50	gold quality
heart	UBERON:0000948	89.48	gold quality
right atrium auricular region	UBERON:0006631	89.38	gold quality
substantia nigra	UBERON:0002038	89.37	gold quality
right frontal lobe	UBERON:0002810	89.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.13	gold quality
muscle tissue	UBERON:0002385	89.08	gold quality
amygdala	UBERON:0001876	88.98	gold quality
temporal lobe	UBERON:0001871	88.95	gold quality
skin of leg	UBERON:0001511	88.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.54	gold quality
lower esophagus	UBERON:0013473	88.52	gold quality
zone of skin	UBERON:0000014	88.49	gold quality
right lobe of liver	UBERON:0001114	88.36	gold quality
Ammon’s horn	UBERON:0001954	88.35	gold quality
popliteal artery	UBERON:0002250	88.30	gold quality
tibial artery	UBERON:0007610	88.29	gold quality
skin of abdomen	UBERON:0001416	88.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting SLC25A26, 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-4668-3P	100.00	68.74	2635
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3616-5P	99.55	67.02	989

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 41.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• SAMC was expressed in mitochondria of all human tissues examined. The role of SAMC is probably to exchange cytosolic SAM for mitochondrial S-adenosylhomocysteine. This is the 1st report of identification & characterization of the human SAMC & its gene. (PMID:14674884)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• SLC25A26 mutations cause various mitochondrial defects, including those affecting RNA stability, protein modification, mitochondrial translation, and the biosynthesis of CoQ10 and lipoic acid. (PMID:26522469)
• overexpression of SLC25A26 in CaSki cells increases mitochondrial SAM availability and promotes hypermethylation of mitochondrial DNA, leading to decreased expression of key respiratory complex subunits, reduction of mitochondrial ATP and release of cytochrome c. (PMID:28118529)
• Identification and characterization of novel compound variants in SLC25A26 associated with combined oxidative phosphorylation deficiency 28. (PMID:34375635)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a26	ENSDARG00000058208
mus_musculus	Slc25a26	ENSMUSG00000045100
rattus_norvegicus	Slc25a26	ENSRNOG00000012831
drosophila_melanogaster	CG4743	FBGN0039357
caenorhabditis_elegans		WBGENE00008364

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), 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 S-adenosylmethionine carrier protein — Q70HW3 (reviewed: Q70HW3)

Alternative names: Solute carrier family 25 member 26

All UniProt accessions (11): Q70HW3, A0A8I5KPW2, A0A8I5KQI7, A0A8I5KRE2, A0A8I5KS24, A0A8I5KTP7, A0A8I5KW47, A0A8I5QKW7, H0YCZ5, H0YF50, H7C430

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial S-adenosyl-L-methionine/S-adenosyl-L-homocysteine antiporter. Mediates the exchange of cytosolic S-adenosyl-L-methionine, the predominant methyl-group donor for macromolecule methylation processes, for mitochondrial S-adenosylhomocysteine(SAH), a by-product of methylation reactions.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Widely expressed. Highly expressed in testis, with moderate expression in brain, heart, kidney, lung, skeletal muscle, pancreas, small intestine and liver, and low expression in spleen.

Disease relevance. Combined oxidative phosphorylation deficiency 28 (COXPD28) [MIM:616794] An autosomal recessive mitochondrial disorder characterized by decreased activities of respiratory chain enzymes, and variable clinical manifestations. Clinical features include episodic metabolic decompensation beginning in infancy, mild muscle weakness, cardiorespiratory insufficiency, developmental delay, or even death. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly inhibited by tannic acid and Bromocresol Purple.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q70HW3-1	1	yes
Q70HW3-2	2
Q70HW3-3	3

RefSeq proteins (9): NP_001158268, NP_001337922, NP_001366139, NP_001387634, NP_001387636, NP_001387638, NP_001387640, NP_001387643, NP_775742 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153

Catalyzed reactions (Rhea), 1 shown:

• S-adenosyl-L-homocysteine(out) + S-adenosyl-L-methionine(in) = S-adenosyl-L-homocysteine(in) + S-adenosyl-L-methionine(out) (RHEA:75479)

UniProt features (21 total): sequence variant 7, transmembrane region 6, splice variant 3, repeat 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70HW3-F1	88.04	0.49

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-425393
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 162 (showing top): GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_TRANSPORT, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_AMINO_ACID_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, AAAGACA_MIR511, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SULFUR_COMPOUND_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, AFFAR_YY1_TARGETS_DN, GOBP_ORGANIC_CATION_TRANSPORT, AGTCAGC_MIR345, GOBP_NUCLEOSIDE_TRANSPORT, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (6): monoatomic ion transport (GO:0006811), S-adenosyl-L-methionine transport (GO:0015805), macromolecule methylation (GO:0043414), mitochondrial S-adenosyl-L-methionine transmembrane transport (GO:1990543), purine nucleoside transmembrane transport (GO:0015860), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (3): S-adenosyl-L-methionine transmembrane transporter activity (GO:0000095), S-adenosyl-L-methionine:S-adenosyl-L-homocysteine antiporter activity (GO:0180003), antiporter activity (GO:0015297)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
S-adenosyl-L-methionine transmembrane transport	2
transport	1
sulfur compound transport	1
methylation	1
macromolecule modification	1
purine-containing compound transmembrane transport	1
nucleoside transmembrane transport	1
amino acid transmembrane transport	1
L-amino acid transport	1
carboxylic acid transmembrane transport	1
sulfur compound transmembrane transporter activity	1
S-adenosyl-L-methionine transmembrane transporter activity	1
L-amino acid transmembrane transporter activity	1
purine nucleoside transmembrane transporter activity	1
antiporter activity	1
modified amino acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A26	MTCH1	Q9NZJ7	725
SLC25A26	MTCH2	Q9Y6C9	703
SLC25A26	THOC7	Q6I9Y2	519
SLC25A26	PSMD6	Q15008	460
SLC25A26	SLC25A53	Q5H9E4	434
SLC25A26	SLC25A36	Q96CQ1	425
SLC25A26	SLC25A38	Q96DW6	423
SLC25A26	SLC25A32	Q9H2D1	419
SLC25A26	SLC25A21	Q9BQT8	418
SLC25A26	SLC25A52	Q3SY17	410
SLC25A26	F6RGN5	F6RGN5	406
SLC25A26	SLC25A3	Q00325	393
SLC25A26	RMND5B	Q96G75	390
SLC25A26	SLC19A1	P41440	389
SLC25A26	MRPL57	Q9BQC6	387

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SPACA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CD80	POTEF	psi-mi:“MI:0914”(association)	0.350
RAMP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
UPK2	IFT56	psi-mi:“MI:0914”(association)	0.350
SLC25A26	NBAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): SLC25A26 (Affinity Capture-MS), MARCH5 (Affinity Capture-Western), SLC25A26 (Affinity Capture-Western), SLC25A26 (Affinity Capture-MS), SLC25A26 (Affinity Capture-MS), SLC25A26 (Biochemical Activity), SLC25A26 (Affinity Capture-MS), SLC25A26 (Affinity Capture-MS), SLC25A26 (Negative Genetic), SLC25A26 (Negative Genetic), SLC25A26 (Reconstituted Complex), SLC25A26 (Protein-peptide), ARFRP1 (Affinity Capture-MS), CRTAP (Affinity Capture-MS), EFR3A (Affinity Capture-MS)

ESM2 similar proteins: A0JN87, A6QR09, F1R4U0, F1RFX9, O22261, O43772, O43808, O70579, O77792, O95258, O97562, O97649, P55851, P55916, P56499, P56501, P70406, P97521, Q08DK4, Q287T7, Q3SZI5, Q4V9P0, Q5R5A8, Q5RD81, Q5RFB7, Q5U680, Q5ZKP7, Q641C8, Q66H23, Q6DG32, Q6GLA2, Q6IZB5, Q70HW3, Q8BMG8, Q8HXY2, Q8R0Z5, Q920G8, Q922G0, Q95J75, Q96A46

Diamond homologs: A0A1D6N272, A1DI57, A2A3V2, A2ASZ8, A2CEQ0, A2R5A0, A3LVX1, A4RF23, A5DIS9, A5DX39, A6RF73, A6SL61, A6ZV78, A7ER02, A7TDX5, B4F8I5, B4FIJ0, B8ZHC9, F4JU70, O04200, O04619, O22261, O43808, O59674, O60029, O70579, O94370, O97649, P04710, P0C546, P10861, P16260, P16261, P25874, P29518, P53257, P55916, Q01888, Q05AQ3, Q08DK7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	72
Likely benign	55
Benign	55

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
222006	NM_001379210.1(SLC25A26):c.443T>G (p.Val148Gly)	Pathogenic
222007	NM_001379210.1(SLC25A26):c.305C>T (p.Ala102Val)	Pathogenic
222008	NM_001379210.1(SLC25A26):c.596C>T (p.Pro199Leu)	Pathogenic
2284160	NM_001379210.1(SLC25A26):c.424C>T (p.Arg142Ter)	Pathogenic
3893218	NM_001379210.1(SLC25A26):c.404A>G (p.Glu135Gly)	Pathogenic
222009	NM_001379210.1(SLC25A26):c.33+1G>A	Likely pathogenic
2637850	NM_001379210.1(SLC25A26):c.191-1G>T	Likely pathogenic

SpliceAI

3697 predictions. Top by Δscore:

Variant	Effect	Δscore
3:66243310:GTG:G	donor_gain	1.0000
3:66243311:TGG:T	donor_loss	1.0000
3:66243313:G:GG	donor_gain	1.0000
3:66243313:GT:G	donor_loss	1.0000
3:66243314:T:TC	donor_loss	1.0000
3:66262047:TTAGG:T	acceptor_loss	1.0000
3:66262048:TA:T	acceptor_loss	1.0000
3:66262049:A:G	acceptor_loss	1.0000
3:66370525:ACAG:A	acceptor_gain	1.0000
3:66370527:AGGCT:A	acceptor_gain	1.0000
3:66370528:GGCTG:G	acceptor_gain	1.0000
3:66370600:AGGGT:A	donor_loss	1.0000
3:66370601:GG:G	donor_gain	1.0000
3:66370602:GG:G	donor_gain	1.0000
3:66370603:G:C	donor_loss	1.0000
3:66370604:T:A	donor_loss	1.0000
3:66380858:TGTT:T	acceptor_gain	1.0000
3:66380860:TTCT:T	acceptor_loss	1.0000
3:66380861:TC:T	acceptor_loss	1.0000
3:66380862:C:CC	acceptor_gain	1.0000
3:66380863:T:G	acceptor_loss	1.0000
3:66381478:CCCAT:C	donor_gain	1.0000
3:66381482:T:C	donor_gain	1.0000
3:66382267:CCTTA:C	donor_loss	1.0000
3:66382268:CTTAC:C	donor_loss	1.0000
3:66382269:TTA:T	donor_loss	1.0000
3:66382270:TACC:T	donor_loss	1.0000
3:66382271:A:AC	donor_gain	1.0000
3:66382271:ACCA:A	donor_loss	1.0000
3:66382272:C:CC	donor_gain	1.0000

AlphaMissense

1742 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:66236603:A:C	K31N	0.990
3:66236603:A:T	K31N	0.990
3:66243211:T:C	F67L	0.990
3:66243213:T:A	F67L	0.990
3:66243213:T:G	F67L	0.990
3:66262089:G:C	K113N	0.989
3:66262089:G:T	K113N	0.989
3:66346370:T:C	F154L	0.989
3:66346372:T:A	F154L	0.989
3:66346372:T:G	F154L	0.989
3:66377727:A:C	S249R	0.989
3:66377729:T:A	S249R	0.989
3:66377729:T:G	S249R	0.989
3:66262085:T:A	V112D	0.987
3:66243206:C:A	A65D	0.986
3:66243305:G:A	G98E	0.985
3:66262101:G:C	Q117H	0.984
3:66262101:G:T	Q117H	0.984
3:66236583:T:C	F25L	0.983
3:66236585:T:A	F25L	0.983
3:66236585:T:G	F25L	0.983
3:66369510:G:C	D201H	0.982
3:66377745:T:C	F255L	0.982
3:66377747:T:A	F255L	0.982
3:66377747:T:G	F255L	0.982
3:66236615:G:C	Q35H	0.981
3:66236615:G:T	Q35H	0.981
3:66243296:C:A	A95D	0.981
3:66236602:A:T	K31I	0.980
3:66369487:C:A	A193D	0.980

dbSNP variants (sampled 300 via entrez): RS1000013420 (3:66279537 G>C), RS1000019978 (3:66378571 A>G), RS1000024330 (3:66183575 T>C), RS1000035385 (3:66310545 G>A,C), RS1000039537 (3:66308685 C>A), RS1000041247 (3:66237795 A>G), RS1000073988 (3:66237956 T>C), RS1000097693 (3:66301899 G>C), RS1000102450 (3:66202615 G>T), RS1000105953 (3:66194454 G>A), RS1000108976 (3:66336241 A>G), RS1000147600 (3:66166593 A>T), RS1000150012 (3:66271663 G>A), RS1000151990 (3:66321589 G>A), RS1000156194 (3:66176739 A>T)

Disease associations

OMIM: gene MIM:611037 | disease phenotypes: MIM:616794, MIM:170400

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 28	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (2): combined oxidative phosphorylation deficiency 28 (MONDO:0014775), hypokalemic periodic paralysis, type 1 (MONDO:0042979)

Orphanet (2): Neonatal severe cardiopulmonary failure due to mitochondrial methylation defect (Orphanet:466784), Hypokalemic periodic paralysis (Orphanet:681)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001635	Congestive heart failure
HP:0002027	Abdominal pain
HP:0002151	Increased circulating lactate concentration
HP:0002878	Respiratory failure
HP:0003200	Ragged-red muscle fibers
HP:0003542	Increased circulating pyruvate concentration
HP:0003593	Infantile onset
HP:0003828	Variable expressivity
HP:0004396	Poor appetite
HP:0004900	Severe lactic acidosis
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0011923	Decreased activity of mitochondrial complex I
HP:0012378	Fatigue

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000872_5	QRS duration	1.000000e-08
GCST003017_2	Colorectal cancer	3.000000e-08
GCST003017_8	Colorectal cancer	2.000000e-08
GCST003844_25	QRS duration	6.000000e-09
GCST005386_4	Binge eating behaviour and bipolar disorder	3.000000e-07
GCST006061_5	Atrial fibrillation	8.000000e-10
GCST006414_77	Atrial fibrillation	1.000000e-10
GCST010321_111	PR interval	1.000000e-17
GCST010796_1579	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1580	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1581	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST90002391_15	Mean corpuscular hemoglobin concentration	9.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005054	QRS complex
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0004528	mean corpuscular hemoglobin concentration

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 — SLC25 mitochondrial vitamin and co-factor carriers subfamily

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
cylindrospermopsin	increases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Amiodarone	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Thiram	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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