ATP5F1D

Summary

ATP5F1D (ATP synthase F1 subunit delta, HGNC:837) is a protein-coding gene on chromosome 19p13.3, encoding ATP synthase F(1) complex subunit delta, mitochondrial (P30049). Subunit delta, 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: 82.0% 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 consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core. Alternatively spliced transcript variants encoding the same isoform have been identified.

Source: NCBI Gene 513 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex V (ATP synthase) deficiency, nuclear type 5 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 175 total — 2 pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 82.0% of screened cell lines
• MANE Select transcript: NM_001687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:837
Approved symbol	ATP5F1D
Name	ATP synthase F1 subunit delta
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099624
Ensembl biotype	protein_coding
OMIM	603150
Entrez	513

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 5 retained_intron

ENST00000215375, ENST00000395633, ENST00000588538, ENST00000589478, ENST00000590265, ENST00000591249, ENST00000591660, ENST00000592624, ENST00000614837, ENST00000906915, ENST00000906916, ENST00000916716

RefSeq mRNA: 2 — MANE Select: NM_001687 NM_001001975, NM_001687

CCDS: CCDS12058

Canonical transcript exons

ENST00000215375 — 4 exons

Exon	Start	End
ENSE00000651441	1242456	1242609
ENSE00000795127	1241751	1241991
ENSE00003551926	1244097	1244185
ENSE00003680378	1244315	1244825

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 293.3761 / max 1580.1498, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172904	293.3761	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.43	gold quality
mucosa of transverse colon	UBERON:0004991	99.34	gold quality
right atrium auricular region	UBERON:0006631	99.27	gold quality
gastrocnemius	UBERON:0001388	99.21	gold quality
lower esophagus mucosa	UBERON:0035834	99.09	gold quality
cardiac atrium	UBERON:0002081	99.03	gold quality
heart left ventricle	UBERON:0002084	98.94	gold quality
cardiac ventricle	UBERON:0002082	98.89	gold quality
right lobe of liver	UBERON:0001114	98.84	gold quality
right frontal lobe	UBERON:0002810	98.84	gold quality
metanephros cortex	UBERON:0010533	98.79	gold quality
body of pancreas	UBERON:0001150	98.77	gold quality
body of stomach	UBERON:0001161	98.77	gold quality
transverse colon	UBERON:0001157	98.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.75	gold quality
muscle of leg	UBERON:0001383	98.72	gold quality
left adrenal gland cortex	UBERON:0035825	98.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.65	gold quality
cingulate cortex	UBERON:0003027	98.64	gold quality
anterior cingulate cortex	UBERON:0009835	98.64	gold quality
right adrenal gland	UBERON:0001233	98.63	gold quality
prefrontal cortex	UBERON:0000451	98.62	gold quality
left adrenal gland	UBERON:0001234	98.59	gold quality
adenohypophysis	UBERON:0002196	98.59	gold quality
cerebellar hemisphere	UBERON:0002245	98.59	gold quality
cerebellar cortex	UBERON:0002129	98.57	gold quality
right adrenal gland cortex	UBERON:0035827	98.56	gold quality
muscle organ	UBERON:0001630	98.55	gold quality
amygdala	UBERON:0001876	98.51	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.33
E-MTAB-8410	yes	13.10
E-CURD-122	yes	11.02
E-MTAB-10042	yes	9.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ATP5F1D, 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-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-1225-3P	97.29	64.60	876

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 82.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Immunohistochemical and immunofluorescent double staining of ATP5D and synaptophysin showed that the reduction of ATP5D was most pronounced at synapses in amyotrophic lateral sclerosis (PMID:27899032)
• These data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation. (PMID:29478781)
• RNA m(1)A methylation regulates glycolysis of cancer cells through modulating ATP5D. (PMID:35867754)
• ATP5D Is a Potential Biomarker for Male Fertility. (PMID:36686378)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5f1d	ENSDARG00000019404
mus_musculus	Atp5f1d	ENSMUSG00000003072
rattus_norvegicus	Atp5f1d	ENSRNOG00000014625
drosophila_melanogaster	ATPsyndelta	FBGN0028342
caenorhabditis_elegans		WBGENE00019061

Protein

Protein identifiers

ATP synthase F(1) complex subunit delta, mitochondrial — P30049 (reviewed: P30049)

Alternative names: ATP synthase F1 subunit delta, F-ATPase delta subunit

All UniProt accessions (2): P30049, A0A087WTL3

UniProt curated annotations — full annotation on UniProt →

Function. Subunit delta, 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. With the central stalk subunit gamma, is essential for the biogenesis of F(1) catalytic part of the ATP synthase complex namely in the formation of F1 assembly intermediate.

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). Component of a complex composed at least by ATPIF1, ATP5F1A, ATP5F1B, ATP5F1C AND ATP5F1E.

Subcellular location. Mitochondrion. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex V deficiency, nuclear type 5 (MC5DN5) [MIM:618120] A mitochondrial disorder characterized by childhood onset of episodic metabolic decompensation featuring lactic acidosis and hyperammonemia accompanied by ketoacidosis or hypoglycemia. Chronic manifestations include developmental delay, easy fatiguability, and 3-methylglutaconic aciduria. The transmission pattern of MC5DN5 is consistent with autosomal recessive inheritance. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the ATPase epsilon chain family.

RefSeq proteins (2): NP_001001975, NP_001678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001469	ATP_synth_F1_dsu/esu	Family
IPR020546	ATP_synth_F1_dsu/esu_N	Domain
IPR036771	ATPsynth_dsu/esu_N	Homologous_superfamily
IPR036794	ATP_F1_dsu/esu_C_sf	Homologous_superfamily
IPR048937	ATPD_C_metazoa	Domain

Pfam: PF02823, PF21335

UniProt features (19 total): strand 8, modified residue 4, helix 3, sequence variant 2, transit peptide 1, chain 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-P30049-F1	85.20	0.70

Functional residue map

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

Post-translational modifications (4): 136, 136, 165, 165

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: 322 (showing top): ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_HDAC1, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_COPPER_ION, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (8): aerobic respiration (GO:0009060), proton motive force-driven ATP synthesis (GO:0015986), mitochondrial proton-transporting ATP synthase complex assembly (GO:0033615), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), response to copper ion (GO:0046688), ATP biosynthetic process (GO:0006754), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): structural molecule activity (GO:0005198), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933), protein binding (GO:0005515), ATP binding (GO:0005524), ADP binding (GO:0043531)

GO Cellular Component (8): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), centriole (GO:0005814), proton-transporting ATP synthase complex (GO:0045259), sperm principal piece (GO:0097228), sperm head-tail coupling apparatus (GO:0120212), 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
mitochondrion	3
cellular anatomical structure	3
proton motive force-driven ATP synthesis	2
adenyl ribonucleotide binding	2
cellular respiration	1
ATP biosynthetic process	1
mitochondrial respiratory chain complex assembly	1
proton-transporting ATP synthase complex assembly	1
oxidative phosphorylation	1
response to metal ion	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
transport	1
monoatomic cation transmembrane transport	1
molecular_function	1
proton channel activity	1
ligase activity	1
binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
microtubule organizing center	1
intracellular membraneless organelle	1
proton-transporting two-sector ATPase complex	1
cation channel complex	1
respiratory chain complex	1
catalytic complex	1
sperm flagellum	1

Protein interactions and networks

STRING

3390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5F1D	ATP5F1A	P25705	982
ATP5F1D	ATP5F1E	P56381	969
ATP5F1D	ATP5F1B	P06576	965
ATP5F1D	ATP5F1C	P36542	958
ATP5F1D	ATP5PD	O75947	847
ATP5F1D	ATP5PB	P24539	843
ATP5F1D	ATP5PO	P48047	834
ATP5F1D	ATP5PF	P18859	759
ATP5F1D	ATP5MC3	P48201	719
ATP5F1D	ATP5ME	P56385	716
ATP5F1D	ATP5MC1	P05496	693
ATP5F1D	ATP5MG	O75964	688
ATP5F1D	NDUFS7	O75251	675
ATP5F1D	UQCRC1	P31930	665
ATP5F1D	COX5A	P20674	664
ATP5F1D	NDUFV1	P49821	664

IntAct

124 interactions, top by confidence:

A	B	Type	Score
ATP5PB	ATP5PD	psi-mi:“MI:0915”(physical association)	0.760
ATP5F1D	ATP5F1E	psi-mi:“MI:0915”(physical association)	0.740
ACKR3	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
ATP5F1D	TNS2	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1D	SRSF11	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	ATP5F1D	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1D	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1D	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1D	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
ATP5MC3	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
ATP5F1D	NDUFB5	psi-mi:“MI:0914”(association)	0.530
ATP5ME	SLC19A2	psi-mi:“MI:0914”(association)	0.530
ATP5PF	SLC19A2	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
BLK	EEF1E1	psi-mi:“MI:0914”(association)	0.350
Kcnk1	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
Atp5f1a	ATP5PD	psi-mi:“MI:0914”(association)	0.350
SMARCB1		psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (234): ATP5D (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5A1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation), ATP5D (Co-fractionation)

ESM2 similar proteins: C0HK54, C0HK56, O02640, O13349, O74190, O74479, P05630, P09457, P0CN60, P0CN61, P0DPG2, P11943, P17783, P30049, P32463, P35434, P53163, P56525, P78700, P78790, Q09544, Q10217, Q12165, Q21018, Q24439, Q41000, Q43744, Q55F42, Q5Y223, Q6C877, Q6C9B1, Q6CRS3, Q6FSD5, Q6ZJS7, Q757N0, Q75EZ3, Q7RYV0, Q8J112, Q8SZA8, Q92196

Diamond homologs: A0LD99, A0LLF7, A1B8P1, A1VFJ6, A3N2U3, A4J998, A4WUM6, A4YKE1, A5CYE1, A5E951, A5EXL3, A5FRQ6, A5UA12, A5UGY8, A6Q4B9, A6UDM0, A6WXX2, A7HT53, A8ZUA2, A9AVV5, A9H9B1, A9M836, A9WGS3, A9WWS1, B0BRX1, B2S7M2, B3H2P2, B3PQ67, B3Q744, B4U9G2, B5ZSN5, B6IPC5, B6JD10, B8EQQ2, B8FGT3, B8G6G5, B9JBZ4, B9JTR1, B9LBL9, C0HK54

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5F1D	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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	9	55.9×	8e-12
Cristae formation	9	33.9×	9e-10
Mitochondrial biogenesis	9	16.4×	6e-07
Aerobic respiration and respiratory electron transport	11	10.6×	8e-07
Organelle biogenesis and maintenance	10	7.2×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	9	61.7×	7e-12
proton motive force-driven mitochondrial ATP synthesis	9	20.2×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	96
Likely benign	61
Benign	10

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
453296	NM_001687.5(ATP5F1D):c.245C>T (p.Pro82Leu)	Pathogenic
489386	NM_001687.5(ATP5F1D):c.317T>G (p.Val106Gly)	Pathogenic

SpliceAI

564 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1242606:TTTG:T	donor_gain	1.0000
19:1242606:TTTGG:T	donor_loss	1.0000
19:1242607:TTG:T	donor_gain	1.0000
19:1242607:TTGGT:T	donor_loss	1.0000
19:1242608:TGGT:T	donor_loss	1.0000
19:1242609:GGT:G	donor_loss	1.0000
19:1242610:G:GC	donor_loss	1.0000
19:1242610:G:GG	donor_gain	1.0000
19:1242611:T:G	donor_loss	1.0000
19:1244087:A:AG	acceptor_gain	1.0000
19:1244088:T:G	acceptor_gain	1.0000
19:1244092:CCCAG:C	acceptor_loss	1.0000
19:1244094:CA:C	acceptor_loss	1.0000
19:1244095:A:AG	acceptor_gain	1.0000
19:1244095:AG:A	acceptor_loss	1.0000
19:1244095:AGT:A	acceptor_gain	1.0000
19:1244096:G:GT	acceptor_gain	1.0000
19:1244096:GT:G	acceptor_gain	1.0000
19:1244096:GTG:G	acceptor_gain	1.0000
19:1244096:GTGA:G	acceptor_gain	1.0000
19:1244182:GGGG:G	donor_gain	1.0000
19:1244183:GGG:G	donor_gain	1.0000
19:1244183:GGGG:G	donor_gain	1.0000
19:1244184:GG:G	donor_gain	1.0000
19:1244184:GGG:G	donor_gain	1.0000
19:1244185:GG:G	donor_gain	1.0000
19:1244186:G:GG	donor_gain	1.0000
19:1244186:GTGA:G	donor_loss	1.0000
19:1244188:G:GG	donor_loss	1.0000
19:1244310:T:A	acceptor_gain	1.0000

AlphaMissense

1061 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1242568:T:A	V85D	0.998
19:1244099:A:C	S100R	0.997
19:1244101:C:A	S100R	0.997
19:1244101:C:G	S100R	0.997
19:1244106:G:A	G102D	0.996
19:1244148:C:A	A116D	0.996
19:1242517:G:A	G68D	0.995
19:1242520:T:C	I69T	0.995
19:1242561:G:T	G83W	0.995
19:1244106:G:T	G102V	0.995
19:1242478:T:A	V55D	0.994
19:1242493:T:A	V60E	0.994
19:1242520:T:A	I69N	0.994
19:1242607:T:C	F98S	0.994
19:1244142:T:C	L114S	0.994
19:1244405:G:C	A159P	0.994
19:1242533:C:A	H73Q	0.993
19:1242533:C:G	H73Q	0.993
19:1244105:G:C	G102R	0.993
19:1244157:C:A	A119D	0.993
19:1241975:T:C	F42S	0.992
19:1242487:T:A	V58E	0.992
19:1242508:G:A	G65E	0.992
19:1242520:T:G	I69S	0.992
19:1242531:C:G	H73D	0.992
19:1242562:G:A	G83E	0.992
19:1244097:T:A	V99E	0.992
19:1244112:T:A	I104N	0.992
19:1244136:T:A	V112E	0.992
19:1244319:C:A	A130D	0.992

dbSNP variants (sampled 300 via entrez): RS1000594236 (19:1243132 T>A), RS1001115819 (19:1242288 A>G), RS1001537027 (19:1242634 G>T), RS1002251968 (19:1241968 T>A,C), RS1002624042 (19:1240348 G>A,T), RS1002999716 (19:1240719 G>A), RS1003127135 (19:1240209 C>A,G), RS1003385367 (19:1244333 G>GA), RS1004131215 (19:1240518 C>G,T), RS1005070548 (19:1243417 C>T), RS1005181888 (19:1242058 G>A,T), RS1005230083 (19:1241618 T>A,C,G), RS1005400903 (19:1242221 C>T), RS1005454905 (19:1242450 C>T), RS1006621141 (19:1242242 C>T)

Disease associations

OMIM: gene MIM:603150 | disease phenotypes: MIM:618120

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex V (ATP synthase) deficiency, nuclear type 5	Strong	Autosomal recessive
mitochondrial proton-transporting ATP synthase complex deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (4): mitochondrial complex V (ATP synthase) deficiency, nuclear type 5 (MONDO:0020858), breast ductal adenocarcinoma (MONDO:0005590), mitochondrial disease (MONDO:0044970), mitochondrial proton-transporting ATP synthase complex deficiency (MONDO:0014471)

Orphanet (1): Mitochondrial disease (Orphanet:68380)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000089	Renal hypoplasia
HP:0000135	Hypogonadism
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001943	Hypoglycemia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066247 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects response to substance, affects cotreatment, decreases expression	4
bisphenol A	affects expression, increases expression, affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	increases expression, decreases expression, affects cotreatment, increases abundance	2
Doxorubicin	affects expression, decreases expression	2
Fluorouracil	affects reaction, decreases expression, affects expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
urushiol	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ochratoxin A	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
gambierol	increases expression, affects cotreatment	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Carmustine	decreases expression	1
Cisplatin	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
CHEMBL5650956	Binding	Binding affinity to human ATP5D 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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9Y9	Ubigene HeLa ATP5F1D KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)