ATP5PB

Summary

ATP5PB (ATP synthase peripheral stalk-membrane subunit b, HGNC:840) is a protein-coding gene on chromosome 1p13.2, encoding ATP synthase peripheral stalk subunit b, mitochondrial (P24539). Subunit b, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. It is a selective cancer dependency (DepMap: 55.0% of cell lines).

This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel.

Source: NCBI Gene 515 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 69 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 55.0% of screened cell lines
• MANE Select transcript: NM_001688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:840
Approved symbol	ATP5PB
Name	ATP synthase peripheral stalk-membrane subunit b
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116459
Ensembl biotype	protein_coding
OMIM	603270
Entrez	515

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000369721, ENST00000369722, ENST00000464154, ENST00000468818, ENST00000483994, ENST00000493119, ENST00000862238, ENST00000862239, ENST00000862240, ENST00000862241, ENST00000962283

RefSeq mRNA: 1 — MANE Select: NM_001688 NM_001688

CCDS: CCDS836

Canonical transcript exons

ENST00000369722 — 7 exons

Exon	Start	End
ENSE00001515567	111460917	111462773
ENSE00001898583	111449464	111449581
ENSE00003479888	111459457	111459636
ENSE00003523404	111449837	111449873
ENSE00003549361	111456630	111456755
ENSE00003646267	111454211	111454356
ENSE00003647812	111456086	111456249

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 194.0641 / max 1905.7424, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4634	193.9522	1827
4632	0.0989	33
4633	0.0129	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.75	gold quality
esophagus squamous epithelium	UBERON:0006920	99.74	gold quality
palpebral conjunctiva	UBERON:0001812	99.72	gold quality
colonic mucosa	UBERON:0000317	99.69	gold quality
choroid plexus epithelium	UBERON:0003911	99.68	gold quality
epithelium of esophagus	UBERON:0001976	99.64	gold quality
jejunal mucosa	UBERON:0000399	99.61	gold quality
biceps brachii	UBERON:0001507	99.61	gold quality
adult organism	UBERON:0007023	99.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.56	gold quality
oral cavity	UBERON:0000167	99.55	gold quality
germinal epithelium of ovary	UBERON:0001304	99.55	gold quality
jejunum	UBERON:0002115	99.55	gold quality
nephron tubule	UBERON:0001231	99.54	gold quality
squamous epithelium	UBERON:0006914	99.53	gold quality
tongue squamous epithelium	UBERON:0006919	99.49	gold quality
epithelium of nasopharynx	UBERON:0001951	99.46	gold quality
tibia	UBERON:0000979	99.45	gold quality
mucosa of transverse colon	UBERON:0004991	99.45	gold quality
parietal pleura	UBERON:0002400	99.42	gold quality
body of tongue	UBERON:0011876	99.41	gold quality
pigmented layer of retina	UBERON:0001782	99.40	gold quality
mammalian vulva	UBERON:0000997	99.39	gold quality
gingival epithelium	UBERON:0001949	99.39	gold quality
sperm	CL:0000019	99.38	gold quality
male germ cell	CL:0000015	99.37	gold quality
gingiva	UBERON:0001828	99.37	gold quality
duodenum	UBERON:0002114	99.36	gold quality
diaphragm	UBERON:0001103	99.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	42.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting ATP5PB, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-892C-5P	99.16	70.56	2116

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Nitration of tyrosine residues 368 and 345 in the beta-subunit elicits FoF1-ATPase activity loss. (PMID:19650768)
• Down-regulation of mitochondrial ATPase by hypermethylation mechanism in chronic myeloid leukemia is associated with multidrug resistance. (PMID:20038517)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5pb	ENSDARG00000011553
mus_musculus	Atp5pb	ENSMUSG00000000563
rattus_norvegicus	Atp5pb	ENSRNOG00000064742
drosophila_melanogaster	ATPsynB	FBGN0019644
caenorhabditis_elegans		WBGENE00000206
caenorhabditis_elegans		WBGENE00000207

Protein

Protein identifiers

ATP synthase peripheral stalk subunit b, mitochondrial — P24539 (reviewed: P24539)

Alternative names: ATP synthase F(0) complex subunit B1, mitochondrial, ATP synthase peripheral stalk-membrane subunit b, ATP synthase proton-transporting mitochondrial F(0) complex subunit B1, ATP synthase subunit b

All UniProt accessions (3): P24539, Q08ET0, Q5QNZ2

UniProt curated annotations — full annotation on UniProt →

Function. Subunit b, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel. These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro. Part of the complex F(0) domain. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.

Subunit / interactions. Component of the ATP synthase complex composed at least of ATP5F1A/subunit alpha, ATP5F1B/subunit beta, ATP5MC1/subunit c (homooctamer), MT-ATP6/subunit a, MT-ATP8/subunit 8, ATP5ME/subunit e, ATP5MF/subunit f, ATP5MG/subunit g, ATP5MK/subunit k, ATP5MJ/subunit j, ATP5F1C/subunit gamma, ATP5F1D/subunit delta, ATP5F1E/subunit epsilon, ATP5PF/subunit F6, ATP5PB/subunit b, ATP5PD/subunit d, ATP5PO/subunit OSCP. ATP synthase complex consists of a soluble F(1) head domain (subunits alpha(3) and beta(3)) - the catalytic core - and a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, e, f, g, k and j). These two domains are linked by a central stalk (subunits gamma, delta, and epsilon) rotating inside the F1 region and a stationary peripheral stalk (subunits F6, b, d, and OSCP).

Subcellular location. Mitochondrion. Mitochondrion inner membrane.

Similarity. Belongs to the eukaryotic ATPase B chain family.

RefSeq proteins (1): NP_001679* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008688	ATP_synth_Bsub_B/MI25	Family
IPR013837	ATP_synth_F0_suB	Family

Pfam: PF05405

UniProt features (22 total): helix 7, modified residue 7, sequence conflict 3, sequence variant 2, transit peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
8H9S	ELECTRON MICROSCOPY	2.53
8H9U	ELECTRON MICROSCOPY	2.61
8H9F	ELECTRON MICROSCOPY	2.69
8H9T	ELECTRON MICROSCOPY	2.77
8KI3	ELECTRON MICROSCOPY	2.89
8H9G	ELECTRON MICROSCOPY	2.95
8H9M	ELECTRON MICROSCOPY	3
8H9V	ELECTRON MICROSCOPY	3.02
8KHF	ELECTRON MICROSCOPY	3.13
8H9J	ELECTRON MICROSCOPY	3.26
8H9Q	ELECTRON MICROSCOPY	3.47
8H9K	ELECTRON MICROSCOPY	3.51
8H9N	ELECTRON MICROSCOPY	3.56
8H9R	ELECTRON MICROSCOPY	3.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24539-F1	84.27	0.60

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 (7): 131, 139, 154, 162, 221, 233, 244

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-163210	Formation of ATP by chemiosmotic coupling
R-HSA-8949613	Cristae formation
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance

MSigDB gene sets: 213 (showing top): SWEET_KRAS_ONCOGENIC_SIGNATURE, GCM_NPM1, HSIAO_HOUSEKEEPING_GENES, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, YY1_Q6, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GCM_PSME1

GO Biological Process (5): proton motive force-driven ATP synthesis (GO:0015986), substantia nigra development (GO:0021762), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): proton transmembrane transporter activity (GO:0015078), protein binding (GO:0005515), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933)

GO Cellular Component (6): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020), proton-transporting ATP synthase complex (GO:0045259)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Mitochondrial biogenesis	1
Metabolism	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
proton motive force-driven ATP synthesis	2
intracellular membrane-bounded organelle	2
ATP biosynthetic process	1
midbrain development	1
neural nucleus development	1
oxidative phosphorylation	1
transport	1
monoatomic cation transmembrane transport	1
monoatomic cation transmembrane transporter activity	1
proton transmembrane transport	1
binding	1
proton channel activity	1
ligase activity	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
cellular anatomical structure	1
proton-transporting two-sector ATPase complex	1
cation channel complex	1
respiratory chain complex	1
catalytic complex	1

Protein interactions and networks

STRING

2294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5PB	ATP5MC1	P05496	909
ATP5PB	ATP5MG	O75964	897
ATP5PB	ATP5F1C	P36542	896
ATP5PB	ATP5PF	P18859	886
ATP5PB	ATP5F1A	P25705	883
ATP5PB	ATP5MF	P56134	874
ATP5PB	ATP5PO	P48047	866
ATP5PB	ATP5PD	O75947	864
ATP5PB	ATP5F1D	P30049	843
ATP5PB	ATP5F1B	P06576	813
ATP5PB	ATP5ME	P56385	792
ATP5PB	ATP5F1E	P56381	782
ATP5PB	ATP5MC3	P48201	750
ATP5PB	UQCRC1	P31930	709
ATP5PB	COX5A	P20674	640

IntAct

237 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
ATP5PB	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.860
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
ATP5PD	ATP5PB	psi-mi:“MI:0915”(physical association)	0.760
ATP5PB	ATP5PD	psi-mi:“MI:0915”(physical association)	0.760
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ATP5PF	ATP5PD	psi-mi:“MI:0914”(association)	0.670
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
FPR2	ARL6IP5	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
ATP5PB	DELE1	psi-mi:“MI:0915”(physical association)	0.560
PADI3	ATP5PB	psi-mi:“MI:0915”(physical association)	0.560
DSN1	ATP5PB	psi-mi:“MI:0915”(physical association)	0.560
FAM117B	ATP5PB	psi-mi:“MI:0915”(physical association)	0.560
ATP5PB	METTL27	psi-mi:“MI:0915”(physical association)	0.560
ATP5PB	HTT	psi-mi:“MI:0915”(physical association)	0.560
ATP5PB	ATXN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (489): ATP5F1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP8 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), FAM134C (Affinity Capture-MS), CERS2 (Affinity Capture-MS), KDM1A (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), ATP5B (Affinity Capture-MS), HSPD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PDP8, B5FVB8, C0HK62, C0HK63, O13349, O74433, O74471, O74988, O75964, O93980, O94373, P00424, P00425, P04039, P05626, P13619, P19511, P22289, P24539, P36147, P90921, Q06405, Q09774, Q12233, Q18803, Q1LUK1, Q20779, Q28852, Q29DG0, Q54QR8, Q5AEM8, Q5RFH0, Q5RFH9, Q6BKZ1, Q6C105, Q6C9E6, Q6CFW6, Q6CS34, Q6CXR8, Q6FJJ0

Diamond homologs: P13619, P19511, P24539, Q5RFH9, Q94516, Q9CQQ7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5PB	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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
Formation of ATP by chemiosmotic coupling	7	29.2×	1e-06
Cristae formation	7	17.7×	2e-05
Mitochondrial protein import	8	9.8×	2e-04
Mitochondrial biogenesis	8	9.8×	2e-04
Protein localization	6	8.3×	5e-03
Aerobic respiration and respiratory electron transport	12	7.8×	1e-05
Mitochondrial protein degradation	8	6.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	7	32.5×	7e-07
proton motive force-driven mitochondrial ATP synthesis	10	15.2×	7e-07
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	10	12.7×	2e-06
phospholipase C-activating G protein-coupled receptor signaling pathway	10	7.6×	2e-04
calcium-mediated signaling	7	7.4×	9e-03
positive regulation of cytosolic calcium ion concentration	9	6.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1048 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111449872:GG:G	donor_gain	1.0000
1:111449873:GG:G	donor_gain	1.0000
1:111456248:AGG:A	donor_loss	1.0000
1:111456249:GGTAA:G	donor_loss	1.0000
1:111456250:G:C	donor_loss	1.0000
1:111456251:T:G	donor_loss	1.0000
1:111456598:ACT:A	acceptor_gain	1.0000
1:111456600:T:A	acceptor_gain	1.0000
1:111456610:T:A	acceptor_gain	1.0000
1:111456613:T:A	acceptor_gain	1.0000
1:111456622:A:AG	acceptor_gain	1.0000
1:111456623:A:G	acceptor_gain	1.0000
1:111456625:TGTAG:T	acceptor_loss	1.0000
1:111456626:GTA:G	acceptor_loss	1.0000
1:111456628:AG:A	acceptor_loss	1.0000
1:111456629:G:GA	acceptor_gain	1.0000
1:111456629:GC:G	acceptor_gain	1.0000
1:111456629:GCA:G	acceptor_gain	1.0000
1:111456629:GCAA:G	acceptor_gain	1.0000
1:111456629:GCAAA:G	acceptor_gain	1.0000
1:111456721:TTCAG:T	donor_gain	1.0000
1:111456752:AAGGG:A	donor_loss	1.0000
1:111456753:AGGG:A	donor_loss	1.0000
1:111456754:GG:G	donor_gain	1.0000
1:111456755:GG:G	donor_gain	1.0000
1:111456755:GGTAG:G	donor_loss	1.0000
1:111456756:GTAGG:G	donor_loss	1.0000
1:111456757:TAGG:T	donor_loss	1.0000
1:111459454:CAG:C	acceptor_loss	1.0000
1:111459455:A:AG	acceptor_gain	1.0000

AlphaMissense

1656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:111459491:G:C	R183P	0.992
1:111456131:A:T	K90I	0.991
1:111459497:G:C	R185P	0.989
1:111460951:T:C	L243P	0.988
1:111456086:G:A	G75E	0.987
1:111456134:A:T	E91V	0.987
1:111459500:T:C	L186P	0.987
1:111454356:G:A	G75R	0.986
1:111454356:G:C	G75R	0.986
1:111459530:G:C	R196P	0.986
1:111459533:T:C	L197P	0.986
1:111456107:G:A	G82E	0.985
1:111454348:G:A	G72D	0.984
1:111454348:G:T	G72V	0.981
1:111456106:G:A	G82R	0.981
1:111456106:G:C	G82R	0.981
1:111454347:G:T	G72C	0.978
1:111456110:T:C	L83P	0.977
1:111454323:T:C	F64L	0.974
1:111454325:C:A	F64L	0.974
1:111454325:C:G	F64L	0.974
1:111456110:T:G	L83R	0.974
1:111454347:G:C	G72R	0.973
1:111456101:G:A	G80E	0.973
1:111456221:T:A	V120D	0.972
1:111460940:C:G	C239W	0.972
1:111456134:A:C	E91A	0.971
1:111456212:G:A	G117D	0.971
1:111456098:T:A	L79H	0.970
1:111456127:T:C	S89P	0.969

dbSNP variants (sampled 300 via entrez): RS1000008481 (1:111454456 G>A), RS1000076570 (1:111452640 C>T), RS1000095505 (1:111461111 A>T), RS1000142370 (1:111448548 C>G), RS1000195140 (1:111448116 G>A), RS1000410714 (1:111452492 G>T), RS1000419911 (1:111449783 A>AGAGCCTGGCGGG), RS1000526200 (1:111449540 C>T), RS1000631508 (1:111455932 A>G,T), RS1000641090 (1:111459515 A>T), RS1001507593 (1:111462173 A>G), RS1001674403 (1:111451755 CTTTG>C), RS1001695417 (1:111452072 A>AT), RS1001766286 (1:111462500 G>C), RS1002004102 (1:111456671 C>A,T)

Disease associations

OMIM: gene MIM:603270 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2	Limited	Autosomal dominant

Mondo (1): hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (MONDO:0859302)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004490_22	Cerebrospinal fluid t-tau:AB1-42 ratio	2.000000e-08
GCST004490_5	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066938 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — F-type ATPase

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.95	Kd	11.28	nM	CHEMBL5653589
7.95	ED50	11.28	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2147916: Binding affinity to human ATP5F1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0113	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	4
sodium arsenite	increases abundance, increases expression, decreases expression	3
chloropicrin	decreases expression	2
Acetaminophen	affects cotreatment, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, increases expression	2
Calcitriol	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
beauvericin	affects cotreatment, decreases expression	1
bufotalin	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
arsenite	affects binding, increases reaction	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
enniatins	affects cotreatment, decreases expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases expression	1
Clozapine	increases expression	1
Diuron	decreases expression	1
Doxorubicin	increases 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
CHEMBL5650958	Binding	Binding affinity to human ATP5F1 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

Clinical trials (associated diseases)

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