ATP5IF1

Summary

ATP5IF1 (ATP synthase inhibitory factor subunit 1, HGNC:871) is a protein-coding gene on chromosome 1p35.3, encoding ATPase inhibitor, mitochondrial (Q9UII2). Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix.

Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of endothelial cell proliferation; and positive regulation of metabolic process. Located in cell surface and mitochondrion.

Source: NCBI Gene 93974 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_016311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:871
Approved symbol	ATP5IF1
Name	ATP synthase inhibitory factor subunit 1
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	ATPI, IP, ATPIP, MGC1167, MGC8898
Ensembl gene	ENSG00000130770
Ensembl biotype	protein_coding
OMIM	614981
Entrez	93974

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000335514, ENST00000465645, ENST00000468425, ENST00000497986, ENST00000922358, ENST00000922359, ENST00000922360

RefSeq mRNA: 3 — MANE Select: NM_016311 NM_016311, NM_178190, NM_178191

CCDS: CCDS319, CCDS320, CCDS44096

Canonical transcript exons

ENST00000335514 — 3 exons

Exon	Start	End
ENSE00001153845	28237837	28238100
ENSE00001815223	28236124	28236270
ENSE00002097527	28236361	28236452

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 321.1753 / max 2419.9329, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1782	317.8622	1828
1781	2.9967	1523
1783	0.2295	104
1784	0.0869	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.48	gold quality
apex of heart	UBERON:0002098	99.42	gold quality
right testis	UBERON:0004534	99.40	gold quality
prefrontal cortex	UBERON:0000451	99.38	gold quality
mucosa of transverse colon	UBERON:0004991	99.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.38	gold quality
superior frontal gyrus	UBERON:0002661	99.34	gold quality
primary visual cortex	UBERON:0002436	99.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.26	gold quality
right atrium auricular region	UBERON:0006631	99.25	gold quality
frontal cortex	UBERON:0001870	99.24	gold quality
hypothalamus	UBERON:0001898	99.22	gold quality
right uterine tube	UBERON:0001302	99.18	gold quality
heart left ventricle	UBERON:0002084	99.16	gold quality
nucleus accumbens	UBERON:0001882	99.15	gold quality
amygdala	UBERON:0001876	99.14	gold quality
duodenum	UBERON:0002114	99.14	gold quality
cerebral cortex	UBERON:0000956	99.13	gold quality
temporal lobe	UBERON:0001871	99.13	gold quality
adenohypophysis	UBERON:0002196	99.09	gold quality
anterior cingulate cortex	UBERON:0009835	99.07	gold quality
pituitary gland	UBERON:0000007	99.05	gold quality
putamen	UBERON:0001874	99.03	gold quality
right frontal lobe	UBERON:0002810	99.03	gold quality
Ammon’s horn	UBERON:0001954	99.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.00	gold quality
brain	UBERON:0000955	98.99	gold quality
caudate nucleus	UBERON:0001873	98.99	gold quality
adult mammalian kidney	UBERON:0000082	98.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	26.57
E-MTAB-6386	no	63.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

6 targeting ATP5IF1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-183-5P	99.31	72.27	1164

Literature-anchored findings (GeneRIF, showing 38)

• The function of ATPase inhibitor protein in the plasma membrane of endothelial cells is probably not limited to regulation of F1F0-ATP synthase catalysis. (PMID:15809073)
• IF(1)-Ca(2+)-CaM complex, forming on plasma membrane, functions in the cellular regulation of HDL endocytosis by hepatocytes. (PMID:17851741)
• the ATPIF1 gene is not considered to contribute to a Chinese family affected with benign familial infantile seizures. (PMID:20374090)
• Findings support that the mitochondrial content of IF1 controls the activity of oxidative phosphorylation mediating the shift of cancer cells to an enhanced aerobic glycolysis. (PMID:20538613)
• The mitochondrial ATPase inhibitory factor 1 triggers a reactive oxygen species -mediated retrograde prosurvival and proliferative response. (PMID:22342343)
• the identification of mitochondrial Atpif1 as a regulator of haem synthesis advances our understanding of the mechanisms regulating mitochondrial haem homeostasis and red blood cell development (PMID:23135403)
• IF1 overexpression is associated with preservation of mitochondrial morphology and ultrastructure, consistent with a central role for IF1 as a determinant of inner membrane architecture and with the role of mitochondrial ultrastructure in the regulation of Cyt c release; data suggest IF1 is an antiapoptotic and potentially tumorigenic factor (PMID:23348567)
• Activation of IF1 degradation acts as the switch that regulates energy metabolism during osteogenic differentiation. (PMID:23722655)
• IF1 as a new determinant of HDL-C that is inversely associated with CHD (PMID:23794714)
• ATPase inhibitory factor 1 (ATPIF1/IF1) was identified as essential for PARK2 recruitment and mitophagy in cultured cells. (PMID:24005319)
• The expression of human ATPase inhibitory factor 1 (hIF1) inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. (PMID:24521670)
• Inhibition of ATPIF1 ameliorates complex III blockade in primary hepatocytes, a cell type afflicted in severe mitochondrial disease. (PMID:24685140)
• promotes hepatocellular carcinoma angiogenesis and metastasis by up-regulation of Snai1 and VEGF transcription (PMID:25042864)
• interaction of IF1 with the complex either directly, by increasing the catalytic activity of the enzyme, or indirectly, by improving the structure of mitochondrial cristae, can increase the oxidative phosphorylation rate in osteosarcoma cells (PMID:25605724)
• IF1 was overexpressed in bladder cancer; concluded that IF1 may be a novel therapeutic target for bladder cancer (PMID:26381881)
• PKA phosphorylates the ATPase inhibitory factor 1 and inactivates its capacity to bind and inhibit the mitochondrial H(+)-ATP synthase. (PMID:26387949)
• These data suggest that in mammalian neurons mitochondria adapt to respiratory stress by upregulating IF1, which exerts a protective role by coordinating pro-survival cell mitophagy and bioenergetics resilience (PMID:26484591)
• Data indicate that oxidative phosphorylation (OXPHOS) is inhibited in the liver of mice expressing human ATPase inhibitory factor 1 (hIF1). (PMID:26595676)
• CF6-induced increase in apoptotic cells was blocked by immature or mature IF1, being accompanied by protein kinase B (PKB) phosphorylation. IF1 antagonizes the pro-apoptotic action of CF6 by relief of intracellular acidification and resultant phosphorylation of PKB. (PMID:26659871)
• Upon IF1 interaction with the ATP synthase both the synthetic and hydrolytic activities of the engine of oxidative phosphorylation are inhibited. (Review) (PMID:26876430)
• this study shows that abnormal expression of ATPase inhibitor, mitochondrial isoform 1 precursor(IF1) may relate to the hyperfunction of immune responses and excessive apoptosis of severe aplastic anemia CD34(+) cells (PMID:27086042)
• The potential role of mitochondrial ATPIF1 in coronary heart disease was reviewed. (PMID:28173810)
• reverse phase protein microarrays identified the glycolysis promoting PKM2 and IF1 proteins as specific biomarkers of dermatomyositis. (PMID:28183315)
• IF1 suppresses programmed cell death. (PMID:28228254)
• Results presently demonstrate, both in vitro and in vivo, that polycyclic aromatic hydrocarbons, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on beta2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. (PMID:28298645)
• results suggest that IF1 overexpression promotes cancer cells survival under temporary anoxic conditions by preserving cellular ATP despite mitochondria dysfunction. (PMID:29097244)
• findings enlighten the cellular biology of IF1 and pave the way to development of additional models that address its role in pathophysiology (PMID:30204502)
• Common p2y13 polymorphisms are associated with plasma inhibitory factor 1 and lipoprotein(a) concentrations, heart rate and body fat mass and may modulate cardiovascular risk. (PMID:30600215)
• Atpif1 gene is involved in the regulation of hemoglobin synthesis (PMID:31894674)
• Inhibition of the mitochondrial ATPase function by IF1 changes the spatiotemporal organization of ATP synthase. (PMID:33065099)
• Circulating Inhibitory Factor 1 levels in adult patients with Prader-Willi syndrome. (PMID:33675216)
• ATPase Inhibitory Factor-1 Disrupts Mitochondrial Ca(2+) Handling and Promotes Pathological Cardiac Hypertrophy through CaMKIIdelta. (PMID:33922643)
• The F1Fo-ATPase inhibitor, IF1, is a critical regulator of energy metabolism in cancer cells. (PMID:33929490)
• ATPase Inhibitory Factor 1-A Novel Marker of Cellular Fitness and Exercise Capacity? (PMID:36499630)
• IF1 ablation prevents ATP synthase oligomerization, enhances mitochondrial ATP turnover and promotes an adenosine-mediated pro-inflammatory phenotype. (PMID:37433784)
• The pro-oncogenic protein IF1 does not contribute to the Warburg effect and is not regulated by PKA in cancer cells. (PMID:37689158)
• Longitudinal Associations Between ATPase Inhibitory Factor 1, Growth Differentiation Factor-15, and Nutritional Status in Older Adults From the MAPT Study. (PMID:37804244)
• The inhibitor protein IF1 from mammalian mitochondria inhibits ATP hydrolysis but not ATP synthesis by the ATP synthase complex. (PMID:38280428)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atp5if1	ENSMUSG00000054428
rattus_norvegicus	Atp5if1	ENSRNOG00000013300
rattus_norvegicus		ENSRNOG00000062699
drosophila_melanogaster	CG13551	FBGN0040660
caenorhabditis_elegans		WBGENE00015248

Paralogs (1): MTHFS (ENSG00000136371)

Protein

Protein identifiers

ATPase inhibitor, mitochondrial — Q9UII2 (reviewed: Q9UII2)

Alternative names: ATP synthase F1 subunit epsilon, Inhibitor of F(1)F(o)-ATPase

All UniProt accessions (2): A0A0B4J230, Q9UII2

UniProt curated annotations — full annotation on UniProt →

Function. Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase. Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme.

Subunit / interactions. Homodimer; represents the active form and is present at a pH value below 6.5. Homotetramer; represents the inactive form and is present at a pH value above 7.0.

Subcellular location. Mitochondrion.

Post-translational modifications. Exhibits variability in chain length, mitochondria have distinct pools of protein cleaved after the 24th, 25th, and 26th amino acid.

Domain organisation. Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 74-106, leaving each N-terminal inhibitory region (residues 26-52) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 26-52) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity.

Similarity. Belongs to the ATPase inhibitor family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UII2-1	1	yes
Q9UII2-2	2
Q9UII2-3	3

RefSeq proteins (3): NP_057395, NP_835497, NP_835498 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007648	ATPase_inhibitor_mt	Family

Pfam: PF04568

UniProt features (12 total): region of interest 3, modified residue 3, splice variant 2, transit peptide 1, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8H9E	ELECTRON MICROSCOPY	2.53
8H9S	ELECTRON MICROSCOPY	2.53
8H9L	ELECTRON MICROSCOPY	2.61
8H9U	ELECTRON MICROSCOPY	2.61
8KI3	ELECTRON MICROSCOPY	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UII2-F1	80.75	0.52

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 (3): 39, 63, 103

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 345 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_MYELOID_CELL_HOMEOSTASIS, MODULE_151, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ERYTHROCYTE_HOMEOSTASIS, DITTMER_PTHLH_TARGETS_UP, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (17): angiogenesis (GO:0001525), negative regulation of endothelial cell proliferation (GO:0001937), response to ischemia (GO:0002931), generation of precursor metabolites and energy (GO:0006091), heme biosynthetic process (GO:0006783), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), erythrocyte differentiation (GO:0030218), negative regulation of hydrolase activity (GO:0051346), mitochondrial depolarization (GO:0051882), reactive oxygen species metabolic process (GO:0072593), positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901030), obsolete positive regulation of proteolysis involved in protein catabolic process (GO:1903052), obsolete regulation of protein targeting to mitochondrion (GO:1903214), regulation of ATP metabolic process (GO:1903578), positive regulation of type 2 mitophagy (GO:1905091), negative regulation of mitochondrial ATP synthesis coupled proton transport (GO:1905707), negative regulation of ATP-dependent activity (GO:0032780)

GO Molecular Function (9): enzyme inhibitor activity (GO:0004857), calmodulin binding (GO:0005516), enzyme binding (GO:0019899), ATPase inhibitor activity (GO:0042030), identical protein binding (GO:0042802), angiostatin binding (GO:0043532), ATPase binding (GO:0051117), mitochondrial proton-transporting ATP synthase complex binding (GO:0140260), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cell surface (GO:0009986), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
metabolic process	2
ATP-dependent activity	2
molecular function inhibitor activity	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
response to stress	1
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
hydrolase activity	1
negative regulation of catalytic activity	1
regulation of hydrolase activity	1
mitochondrion	1
regulation of mitochondrial membrane potential	1
membrane depolarization	1
positive regulation of organelle organization	1
positive regulation of mitochondrial membrane permeability	1
positive regulation of transport	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
ATP metabolic process	1
regulation of purine nucleotide metabolic process	1
type 2 mitophagy	1
positive regulation of mitophagy	1
regulation of type 2 mitophagy	1
proton motive force-driven mitochondrial ATP synthesis	1
regulation of mitochondrial ATP synthesis coupled proton transport	1
negative regulation of ATP biosynthetic process	1
regulation of ATP-dependent activity	1
negative regulation of molecular function	1

Protein interactions and networks

STRING

3718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5IF1	EIF5B	O60841	998
ATP5IF1	TSFM	P43897	830
ATP5IF1	GFM1	Q96RP9	797
ATP5IF1	EIF1	P41567	768
ATP5IF1	MARS1	P56192	711
ATP5IF1	ATP5F1E	P56381	698
ATP5IF1	MARS2	Q96GW9	690
ATP5IF1	MRRF	Q96E11	677
ATP5IF1	MTIF2	P46199	644
ATP5IF1	AARS1	P49588	640
ATP5IF1	MT-ATP8	P03928	629
ATP5IF1	AARS2	Q5JTZ9	625
ATP5IF1	MTIF3	Q9H2K0	614
ATP5IF1	EIF1B	O60739	609
ATP5IF1	RPS16	P17008	599

IntAct

157 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
ATP5IF1	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.740
ATP5IF1	ATP5F1B	psi-mi:“MI:0914”(association)	0.740
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CERS2	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
FPR2	ARL6IP5	psi-mi:“MI:0914”(association)	0.640
PICK1	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
KIF9	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	A2M	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	CHAT	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	DMWD	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	DNM2	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	TOR1A	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1		psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	GLE1	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	GRN	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	GSN	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	HRAS	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
NEFL	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	PMP22	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
ATP5IF1	NUP58	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (211): ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-RNA), CAT (Co-fractionation), GAA (Co-fractionation), RNASET2 (Co-fractionation), UQCRFS1 (Co-fractionation), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS)

ESM2 similar proteins: A1C6F8, A1DH31, A1XQT2, A3KNL5, A3KP48, A8XZB0, F7BK26, O35143, O44441, O64823, O74523, O93980, P01096, P01097, P01098, P02721, P09940, P11950, P13618, P18859, P21571, P37209, P80971, P91928, P97450, Q03344, Q0CXX1, Q1LYB6, Q24407, Q29307, Q3T0E3, Q4X156, Q5BBH7, Q5FVV3, Q5I030, Q5R7J0, Q5RBY3, Q5RFJ9, Q5U509, Q63ZW2

Diamond homologs: A8XZB0, O35143, O44441, P01096, P37209, Q03344, Q29307, Q5RFJ9, Q9UII2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5IF1	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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	40.4×	1e-07
Cristae formation	7	24.5×	3e-06
Mitochondrial biogenesis	7	11.9×	4e-04
Aerobic respiration and respiratory electron transport	8	7.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	7	46.4×	1e-07
proton motive force-driven mitochondrial ATP synthesis	6	13.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

414 predictions. Top by Δscore:

Variant	Effect	Δscore
1:28236267:TCAGG:T	donor_loss	1.0000
1:28236268:CAG:C	donor_loss	1.0000
1:28236269:AGGTA:A	donor_loss	1.0000
1:28236272:T:A	donor_loss	1.0000
1:28236359:A:AG	acceptor_gain	1.0000
1:28236360:G:GA	acceptor_gain	1.0000
1:28236271:G:GG	donor_gain	0.9900
1:28236357:GCAGT:G	acceptor_loss	0.9900
1:28236358:CA:C	acceptor_loss	0.9900
1:28236359:A:AC	acceptor_loss	0.9900
1:28236359:AGTCC:A	acceptor_gain	0.9900
1:28236360:G:GT	acceptor_loss	0.9900
1:28236360:GT:G	acceptor_gain	0.9900
1:28236360:GTC:G	acceptor_gain	0.9900
1:28236360:GTCC:G	acceptor_gain	0.9900
1:28236360:GTCCG:G	acceptor_gain	0.9900
1:28236468:TCCC:T	donor_gain	0.9900
1:28236356:T:TA	acceptor_gain	0.9800
1:28236450:CCG:C	donor_loss	0.9800
1:28236451:CGGTG:C	donor_loss	0.9800
1:28236453:GT:G	donor_loss	0.9800
1:28236454:T:G	donor_loss	0.9800
1:28236455:GAGGC:G	donor_loss	0.9800
1:28236440:A:T	donor_gain	0.9700
1:28237835:A:AG	acceptor_gain	0.9700
1:28237836:G:GG	acceptor_gain	0.9700
1:28237836:GA:G	acceptor_gain	0.9700
1:28236453:G:GG	donor_gain	0.9600
1:28236456:AGGCT:A	donor_loss	0.9600
1:28236439:G:GT	donor_gain	0.9500

AlphaMissense

691 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:28236448:T:C	F59L	0.976
1:28236450:C:A	F59L	0.976
1:28236450:C:G	F59L	0.976
1:28236430:G:C	A53P	0.975
1:28237920:T:C	L88P	0.969
1:28237938:G:C	R94P	0.968
1:28236438:G:C	E55D	0.963
1:28236438:G:T	E55D	0.963
1:28236452:G:C	R60P	0.956
1:28236412:T:C	F47L	0.954
1:28236414:C:A	F47L	0.954
1:28236414:C:G	F47L	0.954
1:28237854:A:C	Q66P	0.954
1:28237866:T:C	L70S	0.953
1:28236443:G:C	R57P	0.948
1:28237862:G:C	A69P	0.948
1:28236445:T:G	Y58D	0.945
1:28237917:G:C	R87P	0.945
1:28237857:T:C	L67P	0.942
1:28237838:G:C	A61P	0.941
1:28236449:T:C	F59S	0.938
1:28236423:A:C	R50S	0.936
1:28236423:A:T	R50S	0.936
1:28236404:G:A	G44D	0.935
1:28237875:A:C	H73P	0.933
1:28236395:G:C	R41P	0.932
1:28236449:T:G	F59C	0.926
1:28237899:A:C	H81P	0.925
1:28236446:A:C	Y58S	0.921
1:28237941:A:C	H95P	0.921

dbSNP variants (sampled 300 via entrez): RS1000733210 (1:28238504 CTA>C), RS1001815117 (1:28238173 G>A), RS1002789144 (1:28236927 A>G), RS1003494926 (1:28236945 G>A,T), RS1003777523 (1:28235907 A>C), RS1003808815 (1:28235667 G>A,T), RS1004535249 (1:28238194 C>G,T), RS1006301614 (1:28237415 C>A,G,T), RS1006821585 (1:28234851 G>A), RS1007339537 (1:28235974 T>A), RS1008245974 (1:28234751 C>T), RS1008277055 (1:28234356 G>A), RS1008665552 (1:28237488 C>A,T), RS1008839767 (1:28237789 T>C), RS1010781165 (1:28238134 T>C,G)

Disease associations

OMIM: gene MIM:614981 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	4
bisphenol A	decreases expression, decreases methylation, affects expression	3
Acetaminophen	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases methylation, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Troglitazone	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression	1
Cisplatin	affects expression	1
Diazinon	increases methylation	1
Diuron	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2SE	Abcam HEK293T ATP5IF1 KO	Transformed cell line	Female
CVCL_SE27	HAP1 ATPIF1 (-) 1	Cancer cell line	Male
CVCL_SE28	HAP1 ATPIF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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