ATP5F1C

Summary

ATP5F1C (ATP synthase F1 subunit gamma, HGNC:833) is a protein-coding gene on chromosome 10p14, encoding ATP synthase F(1) complex subunit gamma, mitochondrial (P36542). Subunit gamma, 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: 69.4% 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 gamma subunit of the catalytic core. Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14.

Source: NCBI Gene 509 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total — 2 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 69.4% of screened cell lines
• MANE Select transcript: NM_001001973

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:833
Approved symbol	ATP5F1C
Name	ATP synthase F1 subunit gamma
Location	10p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165629
Ensembl biotype	protein_coding
OMIM	108729
Entrez	509

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 7 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000335698, ENST00000356708, ENST00000460362, ENST00000460820, ENST00000462760, ENST00000465936, ENST00000472202, ENST00000473809, ENST00000480528, ENST00000493053, ENST00000864423, ENST00000864424, ENST00000864425, ENST00000864426, ENST00000864427, ENST00000864428, ENST00000926764, ENST00000926765

RefSeq mRNA: 3 — MANE Select: NM_001001973 NM_001001973, NM_001320886, NM_005174

CCDS: CCDS31142, CCDS7081

Canonical transcript exons

ENST00000356708 — 10 exons

Exon	Start	End
ENSE00001815091	7807659	7807801
ENSE00003518633	7799772	7799915
ENSE00003518697	7800027	7800091
ENSE00003575354	7798990	7799194
ENSE00003599482	7802758	7802854
ENSE00003600827	7788177	7788263
ENSE00003615216	7797047	7797178
ENSE00003634227	7796121	7796155
ENSE00003647568	7806974	7807010
ENSE00003681866	7802270	7802425

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 230.6256 / max 2049.5429, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103765	215.6682	1827
103764	14.9574	1796

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	99.88	gold quality
left ventricle myocardium	UBERON:0006566	99.74	gold quality
myocardium	UBERON:0002349	99.67	gold quality
vena cava	UBERON:0004087	99.56	gold quality
triceps brachii	UBERON:0001509	99.55	gold quality
cardiac ventricle	UBERON:0002082	99.55	gold quality
heart left ventricle	UBERON:0002084	99.55	gold quality
biceps brachii	UBERON:0001507	99.51	gold quality
body of tongue	UBERON:0011876	99.51	gold quality
deltoid	UBERON:0001476	99.50	gold quality
right adrenal gland	UBERON:0001233	99.49	gold quality
right adrenal gland cortex	UBERON:0035827	99.48	gold quality
left adrenal gland	UBERON:0001234	99.46	gold quality
gluteal muscle	UBERON:0002000	99.46	gold quality
colonic mucosa	UBERON:0000317	99.44	gold quality
adrenal cortex	UBERON:0001235	99.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.44	gold quality
mucosa of transverse colon	UBERON:0004991	99.44	gold quality
left adrenal gland cortex	UBERON:0035825	99.44	gold quality
parotid gland	UBERON:0001831	99.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.41	gold quality
adrenal tissue	UBERON:0018303	99.41	gold quality
ileal mucosa	UBERON:0000331	99.40	gold quality
heart	UBERON:0000948	99.40	gold quality
apex of heart	UBERON:0002098	99.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.39	gold quality
tongue squamous epithelium	UBERON:0006919	99.39	gold quality
renal medulla	UBERON:0000362	99.37	gold quality
cardiac atrium	UBERON:0002081	99.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	46.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting ATP5F1C, 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-607	99.97	73.62	5593
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-626	98.89	66.21	762
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-382-5P	96.71	65.90	762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• These results demonstrated that the 5’-AGUUCCA-3’ immediately downstream from ESE is a muscle-specific exonic splicing silencer (MS-ESS) responsible for exclusion of exon 9 in vivo and in vitro (PMID:11744705)
• A report on the mechanism of exon skipping regulated by Fox-1, using the hF1gamma gene as a model system. (PMID:17686786)
• Studies indicate that F1-ATPase (F1) is a rotary motor protein driven by ATP hydrolysis and the minimum complex of F1 for function as a rotary motor is the alpha3beta3gamma subcomplex. (PMID:23395605)
• Both gamma and delta subunits silenced cells displayed decreased ATP synthase function - lowered rate of ADP-stimulated respiration, a two-fold increased sensitivity of respiration to inhibitor oligomycin, and impaired utilization of mitochondrial membrane potential for ADP phosphorylation. (PMID:29499186)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp5f1c	ENSDARG00000045514
mus_musculus	Atp5f1c	ENSMUSG00000025781
rattus_norvegicus	Atp5f1c	ENSRNOG00000019223
drosophila_melanogaster	ATPsyngamma	FBGN0020235
caenorhabditis_elegans		WBGENE00022089

Protein

Protein identifiers

ATP synthase F(1) complex subunit gamma, mitochondrial — P36542 (reviewed: P36542)

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

All UniProt accessions (1): P36542

UniProt curated annotations — full annotation on UniProt →

Function. Subunit gamma, 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 delta, 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). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Isoform Heart is expressed specifically in the heart and skeletal muscle, which require rapid energy supply. Isoform Liver is expressed in the brain, liver and kidney. Isoform Heart and Isoform Liver are expressed in the skin, intestine, stomach and aorta.

Similarity. Belongs to the ATPase gamma chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
P36542-1	Liver, L	yes
P36542-2	Heart, H

RefSeq proteins (3): NP_001001973, NP_001307815, NP_005165 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000131	ATP_synth_F1_gsu	Family
IPR023632	ATP_synth_F1_gsu_CS	Conserved_site
IPR035968	ATP_synth_F1_ATPase_gsu	Homologous_superfamily

Pfam: PF00231

UniProt features (34 total): modified residue 10, strand 10, helix 9, transit peptide 1, chain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

14 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
8H9F	ELECTRON MICROSCOPY	2.69
8H9I	ELECTRON MICROSCOPY	2.77
8H9T	ELECTRON MICROSCOPY	2.77
8KI3	ELECTRON MICROSCOPY	2.89
8H9M	ELECTRON MICROSCOPY	3
8H9P	ELECTRON MICROSCOPY	3.02
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-P36542-F1	87.86	0.72

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 (10): 197, 270, 39, 49, 55, 115, 115, 146, 154, 154

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-163210	Formation of ATP by chemiosmotic coupling
R-HSA-8949613	Cristae formation
R-HSA-9837999	Mitochondrial protein degradation
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
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 227 (showing top): MORF_MBD4, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, REACTOME_FORMATION_OF_ATP_BY_CHEMIOSMOTIC_COUPLING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (6): oxidative phosphorylation (GO:0006119), ATP biosynthetic process (GO:0006754), proton motive force-driven ATP synthesis (GO:0015986), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): RNA binding (GO:0003723), proton-transporting ATP synthase activity, rotational mechanism (GO:0046933), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (5): 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-5 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Mitochondrial biogenesis	1
Metabolism of proteins	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	3
mitochondrion	2
aerobic respiration	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
ATP biosynthetic process	1
oxidative phosphorylation	1
transport	1
monoatomic cation transmembrane transport	1
nucleic acid binding	1
proton channel activity	1
ligase activity	1
binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
cytoplasm	1
intracellular membrane-bounded organelle	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

3717 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP5F1C	ATP5F1B	P06576	998
ATP5F1C	ATP5F1A	P25705	994
ATP5F1C	ATP5F1D	P30049	958
ATP5F1C	ATP5F1E	P56381	939
ATP5F1C	ATP5PB	P24539	896
ATP5F1C	ATPAF1	Q5TC12	867
ATP5F1C	ATPAF2	Q8N5M1	837
ATP5F1C	ATP5PD	O75947	816
ATP5F1C	ATP5MC3	P48201	814
ATP5F1C	ATP5PO	P48047	811
ATP5F1C	ACER3	Q9NUN7	810
ATP5F1C	ATP5PF	P18859	767
ATP5F1C	ATP5MC1	P05496	758
ATP5F1C	ATP5MG	O75964	757
ATP5F1C	ATP5MF	P56134	710

IntAct

256 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
ATP5PB	ATP5PD	psi-mi:“MI:0915”(physical association)	0.760
ATP5IF1	ATP5F1B	psi-mi:“MI:0914”(association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATP5PB	SLC19A2	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
ATP5F1C	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.620
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
ATP5F1C	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
COQ2	SLC25A5	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	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
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (551): ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5C1 (Co-fractionation)

ESM2 similar proteins: A1K1S1, A1TJ40, A1VIV1, A1W2T6, A4GAH0, A6T471, A9HY41, B0TWS6, B2JJ96, B2UGV0, B3R7L6, B9MBA2, C0HK53, C4KYS4, O01666, O74754, P05435, P05631, P0C1M0, P12113, P26360, P29790, P35435, P36542, P38077, P49377, Q01908, Q06908, Q0C0Z9, Q12GQ1, Q162S8, Q1GEU7, Q1GXM9, Q1LHK9, Q223D5, Q2KU35, Q3SF65, Q41075, Q46VX9, Q4R5B0

Diamond homologs: A1B8N9, A1TJ40, A1UR48, A1W2T6, A3DAR5, A4WUM8, A5CYE3, A5FL19, A5FZ53, A5G9D7, A5V3X4, A5VSE2, A6UDM2, A6WUJ1, A6WXX0, A7HT51, A8HAG4, A8LJR5, A9BPU6, A9H9A6, A9IYW8, A9KX07, A9M838, A9W2R2, A9WWS3, B0T336, B0TQF5, B0UE40, B1ZEE8, B2ICI6, B2JJ96, B2S7M4, B3EA02, B3PQ69, B3QL62, B4RD46, B5ZSN8, B6IPC7, B7KUA3, B8CVU6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP5F1C	“form complex”	“ATP synthase”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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	34.6×	2e-08
Cristae formation	8	21.0×	6e-07
Mitochondrial protein import	10	12.7×	7e-07
Mitochondrial biogenesis	10	12.7×	7e-07
Aerobic respiration and respiratory electron transport	13	8.7×	6e-07
Mitochondrial protein degradation	10	8.7×	2e-05
Protein localization	6	8.7×	4e-03
Organelle biogenesis and maintenance	13	6.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	8	39.4×	7e-09
proton motive force-driven mitochondrial ATP synthesis	12	19.4×	1e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
394756	GRCh37/hg19 10p14(chr10:7377293-9129131)x1	Pathogenic
4682766	GRCh37/hg19 10p14(chr10:7748453-9870680)x1	Pathogenic

SpliceAI

1301 predictions. Top by Δscore:

Variant	Effect	Δscore
10:7788302:G:T	donor_gain	1.0000
10:7788306:G:GT	donor_gain	1.0000
10:7796152:GATA:G	donor_gain	1.0000
10:7796153:ATA:A	donor_gain	1.0000
10:7796154:TA:T	donor_gain	1.0000
10:7796156:G:GG	donor_gain	1.0000
10:7797045:A:AG	acceptor_gain	1.0000
10:7797046:G:GT	acceptor_gain	1.0000
10:7797046:GT:G	acceptor_gain	1.0000
10:7797046:GTC:G	acceptor_gain	1.0000
10:7797046:GTCA:G	acceptor_gain	1.0000
10:7797176:TAGG:T	donor_loss	1.0000
10:7797179:GT:G	donor_loss	1.0000
10:7797180:T:G	donor_loss	1.0000
10:7798987:A:AG	acceptor_gain	1.0000
10:7798987:AAG:A	acceptor_loss	1.0000
10:7798988:A:AG	acceptor_gain	1.0000
10:7798989:G:GC	acceptor_gain	1.0000
10:7798989:GCT:G	acceptor_gain	1.0000
10:7798989:GCTCT:G	acceptor_gain	1.0000
10:7799145:G:GT	donor_gain	1.0000
10:7799149:T:G	donor_gain	1.0000
10:7799190:TATAG:T	donor_loss	1.0000
10:7799191:ATAGG:A	donor_loss	1.0000
10:7799192:TAGGT:T	donor_loss	1.0000
10:7799193:AGG:A	donor_loss	1.0000
10:7799194:GGTAA:G	donor_loss	1.0000
10:7799195:G:T	donor_loss	1.0000
10:7799196:T:A	donor_loss	1.0000
10:7800015:T:A	acceptor_gain	1.0000

AlphaMissense

1955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:7799074:G:A	C103Y	1.000
10:7799075:T:G	C103W	1.000
10:7802386:G:C	A252P	1.000
10:7802398:G:C	A256P	1.000
10:7802403:G:A	M257I	1.000
10:7802403:G:C	M257I	1.000
10:7802403:G:T	M257I	1.000
10:7802411:C:A	A260D	1.000
10:7802794:G:C	R277P	1.000
10:7802799:C:A	R279S	1.000
10:7802800:G:C	R279P	1.000
10:7802804:A:C	Q280H	1.000
10:7802804:A:T	Q280H	1.000
10:7802805:G:C	A281P	1.000
10:7802824:T:C	L287S	1.000
10:7797059:T:C	L35P	0.999
10:7797086:T:A	I44N	0.999
10:7797086:T:C	I44T	0.999
10:7797086:T:G	I44S	0.999
10:7797099:G:A	M48I	0.999
10:7797099:G:C	M48I	0.999
10:7797099:G:T	M48I	0.999
10:7797109:G:C	A52P	0.999
10:7797112:G:C	A53P	0.999
10:7797115:G:C	A54P	0.999
10:7797130:G:C	A59P	0.999
10:7797143:T:C	L63P	0.999
10:7799061:G:C	D99H	0.999
10:7799065:G:C	R100P	0.999
10:7799067:G:A	G101R	0.999

dbSNP variants (sampled 300 via entrez): RS1000178669 (10:7803006 G>T), RS1000229562 (10:7803310 A>C,G), RS1000483253 (10:7789570 C>G,T), RS1000535708 (10:7789946 A>C), RS1000911500 (10:7805696 G>A,T), RS1000929514 (10:7786715 C>T), RS1000947773 (10:7799078 T>C), RS1001021328 (10:7798780 C>T), RS1001097714 (10:7804278 G>C), RS1001179992 (10:7800998 C>T), RS1001230966 (10:7801294 C>T), RS1001496087 (10:7798339 C>T), RS1001537080 (10:7788172 C>A,G,T), RS1001569778 (10:7798067 C>G), RS1001655509 (10:7807598 G>T)

Disease associations

OMIM: gene MIM:108729 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005549_13	Alzheimer’s disease (late onset)	6.000000e-10
GCST009798_43	Asthma	1.000000e-08
GCST009798_79	Asthma	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295752 (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

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

pChembl	Type	Value	Unit	Molecule
5.61	Kd	2429	nM	CHEMBL5653589
5.61	ED50	2429	nM	CHEMBL5653589
5.50	Kd	3133	nM	CHEMBL3752910
5.50	ED50	3133	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 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	2147913: Binding affinity to human ATP5C1 incubated for 45 mins by Kinobead based pull down assay	kd	2.4295	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147913: Binding affinity to human ATP5C1 incubated for 45 mins by Kinobead based pull down assay	kd	3.1333	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
Acetaminophen	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Copper Sulfate	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
acipimox	increases expression	1
brequinar	decreases expression	1
arsenic trichloride	decreases expression, increases abundance, affects cotreatment	1
azoxystrobin	decreases expression	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
fenpyroximate	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119032	Binding	Binding affinity to ATP5C1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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