ATP5ME

Summary

ATP5ME (ATP synthase membrane subunit e, HGNC:846) is a protein-coding gene on chromosome 4p16.3, encoding ATP synthase F(0) complex subunit e, mitochondrial (P56385). Subunit e, 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: 59.0% of cell lines).

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

Source: NCBI Gene 521 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 72 total — 24 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 59.0% of screened cell lines
• MANE Select transcript: NM_007100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:846
Approved symbol	ATP5ME
Name	ATP synthase membrane subunit e
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169020
Ensembl biotype	protein_coding
OMIM	601519
Entrez	521

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000304312, ENST00000505852, ENST00000506525, ENST00000515116, ENST00000515202, ENST00000895154, ENST00000932115, ENST00000932116, ENST00000932117, ENST00000932118

RefSeq mRNA: 1 — MANE Select: NM_007100 NM_007100

CCDS: CCDS3337

Canonical transcript exons

ENST00000304312 — 4 exons

Exon	Start	End
ENSE00001166639	673912	673966
ENSE00001233468	674212	674276
ENSE00003521922	673303	673401
ENSE00003628619	672436	672519

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 114.4877 / max 862.3523, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50992	86.6523	1826
50994	18.3899	1815
50993	7.9805	1722
50995	1.4650	842

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.87	gold quality
cardiac ventricle	UBERON:0002082	99.78	gold quality
heart left ventricle	UBERON:0002084	99.78	gold quality
mucosa of transverse colon	UBERON:0004991	99.75	gold quality
right atrium auricular region	UBERON:0006631	99.75	gold quality
tendon of biceps brachii	UBERON:0008188	99.74	gold quality
cardiac atrium	UBERON:0002081	99.73	gold quality
heart	UBERON:0000948	99.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.67	gold quality
medial globus pallidus	UBERON:0002477	99.66	gold quality
amygdala	UBERON:0001876	99.65	gold quality
heart right ventricle	UBERON:0002080	99.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.65	gold quality
substantia nigra	UBERON:0002038	99.64	gold quality
nucleus accumbens	UBERON:0001882	99.63	gold quality
spinal cord	UBERON:0002240	99.63	gold quality
globus pallidus	UBERON:0001875	99.62	gold quality
midbrain	UBERON:0001891	99.62	gold quality
corpus callosum	UBERON:0002336	99.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.62	gold quality
caudate nucleus	UBERON:0001873	99.61	gold quality
putamen	UBERON:0001874	99.60	gold quality
right frontal lobe	UBERON:0002810	99.60	gold quality
cingulate cortex	UBERON:0003027	99.60	gold quality
anterior cingulate cortex	UBERON:0009835	99.60	gold quality
adenohypophysis	UBERON:0002196	99.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.59	gold quality
cervix squamous epithelium	UBERON:0006922	99.59	gold quality
renal medulla	UBERON:0000362	99.58	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	1365.82
E-MTAB-8410	yes	49.65
E-HCAD-10	yes	36.70
E-HCAD-1	yes	18.24
E-ANND-3	yes	17.86
E-HCAD-13	yes	13.49
E-CURD-122	yes	12.54
E-MTAB-10042	yes	11.83
E-MTAB-7303	no	1854.70
E-MTAB-10596	no	1503.87
E-MTAB-9388	no	1379.01
E-MTAB-7606	no	331.81
E-GEOD-135922	no	8.17

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• results suggest that antisense of hAS-e can inhibit cell proliferation through the MAP kinase pathway (PMID:11939412)
• This is the first report identifying caspase-3 as a substrate protein of Hsp90. (PMID:16682002)
• The inhibitory activity against mitochondria and F(1)F(0)-ATP synthase is not limited to atrazine but is likely to be applicable to other triazine-based compounds. (PMID:18060860)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5meb	ENSDARG00000068940
danio_rerio	atp5mea	ENSDARG00000078113
mus_musculus	Atp5me	ENSMUSG00000050856
rattus_norvegicus	Atp5me	ENSRNOG00000000064
caenorhabditis_elegans		WBGENE00011015

Protein

Protein identifiers

ATP synthase F(0) complex subunit e, mitochondrial — P56385 (reviewed: P56385)

Alternative names: ATP synthase membrane subunit e

All UniProt accessions (1): P56385

UniProt curated annotations — full annotation on UniProt →

Function. Subunit e, 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.

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 ATPase e subunit family.

RefSeq proteins (1): NP_009031* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008386	ATP_synth_F0_esu_mt	Family

Pfam: PF05680

UniProt features (6 total): chain 2, modified residue 2, initiator methionine 1, helix 1

Structure

Experimental structures (PDB)

10 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
8H9M	ELECTRON MICROSCOPY	3
8H9V	ELECTRON MICROSCOPY	3.02
8KHF	ELECTRON MICROSCOPY	3.13
8H9J	ELECTRON MICROSCOPY	3.26
8H9Q	ELECTRON MICROSCOPY	3.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56385-F1	91.62	0.83

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 (2): 34, 66

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: 197 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, JI_RESPONSE_TO_FSH_UP, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KYNG_DNA_DAMAGE_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP

GO Biological Process (5): proton motive force-driven ATP synthesis (GO:0015986), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), ATP biosynthetic process (GO:0006754), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): proton transmembrane transporter activity (GO:0015078), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), proton-transporting ATP synthase complex (GO:0045259), membrane (GO:0016020)

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
proton motive force-driven ATP synthesis	2
binding	2
ATP biosynthetic process	1
mitochondrion	1
oxidative phosphorylation	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
transport	1
monoatomic cation transmembrane transport	1
monoatomic cation transmembrane transporter activity	1
proton transmembrane transport	1
proton channel activity	1
ligase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
proton-transporting two-sector ATPase complex	1
cation channel complex	1
respiratory chain complex	1
catalytic complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1695 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5ME	ATP5MG	O75964	856
ATP5ME	ATP5MF	P56134	826
ATP5ME	ATP5PF	P18859	809
ATP5ME	ATP5PB	P24539	792
ATP5ME	ATP5PD	O75947	791
ATP5ME	ATP5F1E	P56381	774
ATP5ME	ATP5PO	P48047	759
ATP5ME	ATP5F1A	P25705	720
ATP5ME	ATP5F1D	P30049	716
ATP5ME	ATP5F1B	P06576	700
ATP5ME	ATP5F1C	P36542	685
ATP5ME	UQCRQ	O14949	667
ATP5ME	COX5B	P10606	656
ATP5ME	COX7A2	P14406	654
ATP5ME	NDUFA5	Q16718	623

IntAct

118 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
ATP5PB	ATP5PD	psi-mi:“MI:0915”(physical association)	0.760
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
ATP5ME	SPG21	psi-mi:“MI:0915”(physical association)	0.560
ATP5ME	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
ATP5ME	SLC19A2	psi-mi:“MI:0914”(association)	0.530
ATP5F1B	SCAMP2	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
SPRYD4	ATP5MG	psi-mi:“MI:0914”(association)	0.500
LARS1	ATP5ME	psi-mi:“MI:0915”(physical association)	0.400
ATP5ME	CHMP2B	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ATP5ME		psi-mi:“MI:0915”(physical association)	0.370
ERBB3	ATP5ME	psi-mi:“MI:0915”(physical association)	0.370
ZNF16	ATP5ME	psi-mi:“MI:0915”(physical association)	0.370
BLK	EEF1E1	psi-mi:“MI:0914”(association)	0.350
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Lck	TLE5	psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Kcnk1	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350
KIF14	URB1	psi-mi:“MI:0914”(association)	0.350
TOMM40	NOS1AP	psi-mi:“MI:0914”(association)	0.350
CCDC14	TBC1D31	psi-mi:“MI:0914”(association)	0.350

BioGRID (166): ATP5I (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation), ATP5I (Co-fractionation)

ESM2 similar proteins: A2VDV9, A5PJ82, C0HLM6, D2H617, D3Z7Q2, E2R5I0, E7EXZ6, F1MDB2, F6USH3, G1QDE8, G1S9B8, O00483, O95563, P00130, P00430, P12633, P13182, P29419, P38718, P56385, P80432, Q01321, Q06185, Q0MQ97, Q0MQ98, Q0MQ99, Q28851, Q2NKS2, Q3SZ44, Q4FZG9, Q5R4Z3, Q5RBW2, Q5RCY6, Q5RDZ8, Q5REX0, Q62425, Q69YU5, Q6GP51, Q8N5G0, Q8R1I1

Diamond homologs: P12633, P29419, P56385, Q00361, Q06185, Q5RBW2, Q9MYT8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5ME	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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	8	47.6×	1e-09
Cristae formation	9	32.4×	1e-09
Amino acid transport across the plasma membrane	6	18.8×	7e-05
Mitochondrial biogenesis	9	15.7×	7e-07
Aerobic respiration and respiratory electron transport	12	11.1×	1e-07
Protein localization	5	9.9×	8e-03
Mitochondrial protein degradation	8	9.5×	1e-04
R-HSA-425393	7	9.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	8	51.8×	1e-09
proton motive force-driven mitochondrial ATP synthesis	10	21.2×	2e-08
amino acid transport	6	15.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	3
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1047902	GRCh37/hg19 4p16.3(chr4:374557-745174)	Pathogenic
1070482	NC_000004.11:g.(?493125)(998181_?)del	Pathogenic
1341163	GRCh37/hg19 4p16.3(chr4:68345-1675143)x1	Pathogenic
147744	GRCh38/hg38 4p16.3(chr4:51519-1405362)x1	Pathogenic
153530	GRCh38/hg38 4p16.3(chr4:68453-1997458)x1	Pathogenic
155105	GRCh38/hg38 4p16.3(chr4:36424-1956092)x1	Pathogenic
155257	GRCh38/hg38 4p16.3(chr4:72555-2689579)x1	Pathogenic
161057	GRCh38/hg38 4p16.3(chr4:72555-2108607)x1	Pathogenic
1703575	Single allele	Pathogenic
1713277	NC_000004.12:g.670405_677862del	Pathogenic
1807847	GRCh37/hg19 4p16.3(chr4:68346-2437290)x1	Pathogenic
2423740	NC_000004.11:g.(?520808)(1020391_?)del	Pathogenic
2685098	GRCh37/hg19 4p16.3(chr4:68346-2681414)x1	Pathogenic
57159	GRCh38/hg38 4p16.3(chr4:72555-2108607)x1	Pathogenic
57898	GRCh38/hg38 4p16.3(chr4:56878-2213205)x1	Pathogenic
57903	GRCh38/hg38 4p16.3(chr4:72555-2325477)x1	Pathogenic
59417	GRCh38/hg38 4p16.3(chr4:85149-1919505)x1	Pathogenic
59418	GRCh38/hg38 4p16.3(chr4:85149-2008535)x1	Pathogenic
59419	GRCh38/hg38 4p16.3(chr4:336191-2213205)x1	Pathogenic
831909	NC_000004.12:g.(?635880)(676939_?)del	Pathogenic
929396	GRCh37/hg19 4p16.3-11(chr4:49450-49620898)x3	Pathogenic
979456	GRCh37/hg19 4p16.3(chr4:1-1328868)x1	Pathogenic
979458	GRCh37/hg19 4p16.3(chr4:68345-2137211)x1	Pathogenic
979459	GRCh37/hg19 4p16.3(chr4:68345-2503033)x3	Pathogenic
148311	GRCh38/hg38 4p16.3(chr4:36424-1581567)x3	Likely pathogenic
1703660	GRCh37/hg19 4p16.3(chr4:68345-1512353)	Likely pathogenic
3248541	NM_000283.4(PDE6B):c.2503+2T>C	Likely pathogenic

SpliceAI

471 predictions. Top by Δscore:

Variant	Effect	Δscore
4:673910:A:AC	donor_gain	1.0000
4:673911:C:CC	donor_gain	1.0000
4:672527:C:CT	acceptor_gain	0.9900
4:672534:T:C	acceptor_gain	0.9900
4:672534:T:TC	acceptor_gain	0.9900
4:673402:C:CC	acceptor_gain	0.9900
4:673410:CGGAA:C	acceptor_gain	0.9900
4:673414:A:AC	acceptor_gain	0.9900
4:673414:A:C	acceptor_gain	0.9900
4:672528:G:T	acceptor_gain	0.9800
4:672533:G:C	acceptor_gain	0.9800
4:673399:AATCT:A	acceptor_loss	0.9800
4:673400:ATCTG:A	acceptor_loss	0.9800
4:673401:TCTGT:T	acceptor_loss	0.9800
4:673403:T:G	acceptor_loss	0.9800
4:672521:T:C	acceptor_gain	0.9700
4:672533:G:GC	acceptor_gain	0.9700
4:673398:TAAT:T	acceptor_gain	0.9700
4:672520:C:CC	acceptor_gain	0.9600
4:672521:T:TC	acceptor_gain	0.9600
4:672527:C:T	acceptor_gain	0.9600
4:673397:GTAAT:G	acceptor_gain	0.9600
4:673400:AT:A	acceptor_gain	0.9600
4:673406:T:C	acceptor_gain	0.9600
4:673411:G:T	acceptor_gain	0.9600
4:673732:AGAAG:A	donor_gain	0.9600
4:673298:CGTA:C	donor_loss	0.9500
4:673299:GTAC:G	donor_loss	0.9500
4:673300:TA:T	donor_loss	0.9500
4:673301:A:AG	donor_loss	0.9500

AlphaMissense

436 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:673950:G:T	A18D	0.993
4:673926:C:T	G26E	0.989
4:673938:C:T	G22D	0.985
4:673917:C:G	R29P	0.984
4:673939:C:G	G22R	0.984
4:673947:A:T	L19Q	0.983
4:673930:A:C	Y25D	0.981
4:673932:G:T	A24D	0.981
4:673384:C:G	A37P	0.979
4:673962:C:T	G14D	0.979
4:674216:A:G	I11T	0.979
4:673924:C:G	A27P	0.978
4:673963:C:G	G14R	0.977
4:674212:C:A	K12N	0.976
4:674212:C:G	K12N	0.976
4:673957:A:C	Y16D	0.975
4:673947:A:G	L19P	0.973
4:674216:A:T	I11N	0.973
4:673935:A:T	V23E	0.971
4:673391:T:A	K34N	0.970
4:673391:T:G	K34N	0.970
4:673951:C:G	A18P	0.969
4:673927:C:G	G26R	0.967
4:673927:C:T	G26R	0.967
4:673395:A:G	L33P	0.965
4:673960:G:T	R15S	0.965
4:674216:A:C	I11S	0.962
4:674219:A:T	L10H	0.961
4:673959:C:G	R15P	0.959
4:673923:G:T	A27D	0.957

dbSNP variants (sampled 300 via entrez): RS1001512894 (4:673541 A>G), RS1001610147 (4:672978 G>C), RS1002173072 (4:673763 C>A), RS1002450535 (4:675821 G>A,T), RS1003211430 (4:673744 T>C,G), RS1003283993 (4:673977 G>A), RS1004508538 (4:674340 G>C), RS1004539506 (4:674471 G>A,T), RS1004762690 (4:674372 C>A,G,T), RS1006519520 (4:674866 G>A,T), RS1006547046 (4:672593 G>A,T), RS1007333084 (4:675330 T>G), RS1008217134 (4:673444 T>C), RS1008437231 (4:675189 C>T), RS1009188843 (4:672309 G>A,T)

Disease associations

OMIM: gene MIM:601519 | disease phenotypes: MIM:209850, MIM:616917, MIM:613801

GenCC curated gene-disease

Mondo (3): autism (MONDO:0005260), intellectual disability, autosomal recessive 53 (MONDO:0014832), retinitis pigmentosa 40 (MONDO:0013429)

Orphanet (2): Early-onset epilepsy-intellectual disability-brain anomalies syndrome (Orphanet:488635), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067089 (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
6.28	Kd	531.2	nM	CHEMBL5653589
6.28	ED50	531.2	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	2147918: Binding affinity to human ATP5I incubated for 45 mins by Kinobead based pull down assay	kd	0.5312	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation, increases methylation	4
sodium arsenite	decreases expression, increases expression	3
Doxorubicin	affects response to substance, increases expression	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
bicalutamide	increases expression	1
phenethyl isothiocyanate	affects binding	1
K 7174	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	increases expression	1
5-hydroxythalidomide	affects binding	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Catechin	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	increases expression	1
Ivermectin	decreases expression	1
Rotenone	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
CHEMBL5650960	Binding	Binding affinity to human ATP5I 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: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SE12	HAP1 ATP5I (-) 1	Cancer cell line	Male
CVCL_SE13	HAP1 ATP5I (-) 2	Cancer cell line	Male
CVCL_SE14	HAP1 ATP5I (-) 3	Cancer cell line	Male
CVCL_XL73	HAP1 ATP5I (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms