mitochondrial proton-transporting ATP synthase complex deficiency

Summary

mitochondrial proton-transporting ATP synthase complex deficiency (MONDO:0014471) is a disease (an umbrella term covering 8 Mondo subtypes) with 8 cohort genes. The dominant Reactome pathway is Formation of ATP by chemiosmotic coupling (6 cohort genes).

At a glance

• Umbrella term: 8 Mondo subtypes
• Cohort genes: 8
• ClinVar variants: 1
• Phenotypes (HPO): 40

Clinical features

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001298	Encephalopathy	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001639	Hypertrophic cardiomyopathy	Frequent (30-79%)
HP:0001644	Dilated cardiomyopathy	Frequent (30-79%)
HP:0001987	Hyperammonemia	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0003128	Lactic acidosis	Frequent (30-79%)
HP:0003348	Hyperalaninemia	Frequent (30-79%)
HP:0003535	3-Methylglutaconic aciduria	Frequent (30-79%)
HP:0009830	Peripheral neuropathy	Frequent (30-79%)
HP:0011675	Arrhythmia	Frequent (30-79%)
HP:0012758	Neurodevelopmental delay	Frequent (30-79%)
HP:0000089	Renal hypoplasia	Occasional (5-29%)
HP:0000135	Hypogonadism	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000510	Rod-cone dystrophy	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0001254	Lethargy	Occasional (5-29%)
HP:0001258	Spastic paraplegia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002445	Tetraplegia	Occasional (5-29%)
HP:0003546	Exercise intolerance	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0032794	Myoclonic seizure	Occasional (5-29%)
HP:0000602	Ophthalmoplegia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial proton-transporting ATP synthase complex deficiency
Mondo ID	MONDO:0014471
OMIM	604273
Orphanet	254913
DOID	DOID:0111143
ICD-11	902255625
UMLS	C4757950
MedGen	1655626
GARD	0018649
Is cancer (heuristic)	no

Also known as: isolated ATP synthase deficiency · isolated mitochondrial respiratory chain complex V deficiency

Data availability: 1 ClinVar variant · 7 GenCC gene-disease records · 4 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › combined oxidative phosphorylation deficiency › mitochondrial proton-transporting ATP synthase complex deficiency

Related subtypes (57): severe X-linked mitochondrial encephalomyopathy, hepatoencephalopathy due to combined oxidative phosphorylation defect type 1, combined oxidative phosphorylation defect type 2, fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, combined oxidative phosphorylation defect type 4, hypotonia with lactic acidemia and hyperammonemia, combined oxidative phosphorylation defect type 7, combined oxidative phosphorylation defect type 8, combined oxidative phosphorylation defect type 9, mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, combined oxidative phosphorylation defect type 11, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, combined oxidative phosphorylation defect type 13, combined oxidative phosphorylation defect type 14, combined oxidative phosphorylation defect type 15, infantile hypertrophic cardiomyopathy due to MRPL44 deficiency, combined oxidative phosphorylation defect type 17, growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome, combined oxidative phosphorylation deficiency 19, combined oxidative phosphorylation defect type 20, combined oxidative phosphorylation defect type 21, combined oxidative phosphorylation defect type 23, combined oxidative phosphorylation defect type 24, combined oxidative phosphorylation defect type 25, combined oxidative phosphorylation defect type 26, combined oxidative phosphorylation defect type 27, combined oxidative phosphorylation deficiency 28, combined oxidative phosphorylation deficiency 29, combined oxidative phosphorylation defect type 30, lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome, combined oxidative phosphorylation deficiency 40, combined oxidative phosphorylation deficiency 41, combined oxidative phosphorylation deficiency 42, combined oxidative phosphorylation deficiency 43, combined oxidative phosphorylation deficiency 44, combined oxidative phosphorylation deficiency 52, combined oxidative phosphorylation deficiency 53, combined oxidative phosphorylation deficiency 54, combined oxidative phosphorylation deficiency 37, combined oxidative phosphorylation deficiency 38, combined oxidative phosphorylation deficiency 39, combined oxidative phosphorylation deficiency 45, combined oxidative phosphorylation deficiency 46, combined oxidative phosphorylation deficiency 47, combined oxidative phosphorylation deficiency 48, combined oxidative phosphorylation deficiency 51, combined oxidative phosphorylation deficiency 32, combined oxidative phosphorylation deficiency 33, combined oxidative phosphorylation deficiency 34, combined oxidative phosphorylation deficiency 35, combined oxidative phosphorylation deficiency 36, combined oxidative phosphorylation deficiency 55, combined oxidative phosphorylation deficiency 56, combined oxidative phosphorylation deficiency 57, combined oxidative phosphorylation deficiency 58, combined oxidative phosphorylation deficiency 59, combined oxidative phosphorylation deficiency 60

Subtypes (8): mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, mitochondrial complex V (ATP synthase) deficiency, nuclear type 3, mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B, combined oxidative phosphorylation deficiency 22, mitochondrial complex 5 (ATP synthase) deficiency, mitochondrial type 1, mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6, mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A, mitochondrial complex V (ATP synthase) deficiency, nuclear type 7

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
203989	NM_017866.6(TMEM70):c.117_118dup (p.Ser40fs)	TMEM70	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 33 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ATP5F1A	Strong	Autosomal dominant	mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A	7
ATP5F1D	Strong	Autosomal recessive	mitochondrial complex V (ATP synthase) deficiency, nuclear type 5	4
ATP5F1E	Strong	Autosomal recessive	mitochondrial complex V (ATP synthase) deficiency, nuclear type 3	4
ATPAF2	Supportive	Autosomal recessive	mitochondrial proton-transporting ATP synthase complex deficiency	4
MT-ATP6	Supportive	Autosomal recessive	mitochondrial proton-transporting ATP synthase complex deficiency	8
MT-ATP8	Supportive	Autosomal recessive	mitochondrial proton-transporting ATP synthase complex deficiency	3
ATP5F1B	Limited	Autosomal dominant	mitochondrial proton-transporting ATP synthase complex deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATPAF2	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:104	Leber hereditary optic neuropathy
MT-ATP6	Orphanet:225154	Familial infantile bilateral striatal necrosis
MT-ATP6	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ATP6	Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia
MT-ATP6	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP6	Orphanet:644	NARP syndrome
MT-ATP8	Orphanet:254913	Isolated ATP synthase deficiency
MT-ATP8	Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy
MT-ATP8	Orphanet:480	Kearns-Sayre syndrome
ATP5F1A	Orphanet:254913	Isolated ATP synthase deficiency
ATP5F1D	Orphanet:254913	Isolated ATP synthase deficiency
ATP5F1E	Orphanet:254913	Isolated ATP synthase deficiency
TMEM70	Orphanet:1194	TMEM70-related mitochondrial encephalo-cardio-myopathy

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATPAF2	HGNC:18802	ENSG00000171953	Q8N5M1	ATP synthase mitochondrial F1 complex assembly factor 2	gencc
MT-ATP6	HGNC:7414	ENSG00000198899	P00846	ATP synthase F(0) complex subunit a	gencc
MT-ATP8	HGNC:7415	ENSG00000228253	P03928	ATP synthase F(0) complex subunit 8	gencc
ATP5F1A	HGNC:823	ENSG00000152234	P25705	ATP synthase F(1) complex subunit alpha, mitochondrial	gencc
ATP5F1B	HGNC:830	ENSG00000110955	P06576	ATP synthase F(1) complex subunit beta, mitochondrial	gencc
ATP5F1D	HGNC:837	ENSG00000099624	P30049	ATP synthase F(1) complex subunit delta, mitochondrial	gencc
ATP5F1E	HGNC:838	ENSG00000124172	P56381	ATP synthase F(1) complex subunit epsilon, mitochondrial	gencc
TMEM70	HGNC:26050	ENSG00000175606	Q9BUB7	Transmembrane protein 70, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATPAF2	ATP synthase mitochondrial F1 complex assembly factor 2	Plays a role in the assembly of the F1 component of the mitochondrial ATP synthase (ATPase).
MT-ATP6	ATP synthase F(0) complex subunit a	Subunit a, 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 th…
MT-ATP8	ATP synthase F(0) complex subunit 8	Subunit 8, 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 th…
ATP5F1A	ATP synthase F(1) complex subunit alpha, mitochondrial	Subunit alpha, 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 o…
ATP5F1B	ATP synthase F(1) complex subunit beta, mitochondrial	Catalytic subunit beta, 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 co…
ATP5F1D	ATP synthase F(1) complex subunit delta, mitochondrial	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 o…
ATP5F1E	ATP synthase F(1) complex subunit epsilon, mitochondrial	Subunit epsilon, 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…
TMEM70	Transmembrane protein 70, mitochondrial	Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC1 through its interaction.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	8	1.8×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATPAF2	Other/Unknown	no		ATP12_ATP_synth-F1-assembly, ATP12_ortho_dom_sf, ATP12_ATP_synth-F1-assembly_N
MT-ATP6	Other/Unknown	no		ATP_synth_F0_asu, ATP_synth_F0_asu_AS, F0_ATP_A_sf
MT-ATP8	Other/Unknown	no		ATP8_metazoa, ATP8_mammal
ATP5F1A	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATP_synth_asu_C, ATPase_F1/V1/A1_a/bsu_N
ATP5F1B	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, AAA+_ATPase, ATPase_F1/V1/A1_a/bsu_N
ATP5F1D	Other/Unknown	no		ATP_synth_F1_dsu/esu, ATP_synth_F1_dsu/esu_N, ATPsynth_dsu/esu_N
ATP5F1E	Other/Unknown	no		ATP_synth_F1_esu_mt, ATP_synth_F1_esu_sf_mt
TMEM70	Other/Unknown	no		TMEM70, TMEM70/TMEM186/TMEM223

Expression context

Cohort genes with no expression data: 0.

8 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
renal medulla	2
apex of heart	2
left testis	1
right testis	1
descending thoracic aorta	1
left uterine tube	1
mucosa of stomach	1
gastrocnemius	1
right lung	1
right ovary	1
esophagus squamous epithelium	1
heart right ventricle	1
cardiac ventricle	1
heart left ventricle	1
mucosa of transverse colon	1
cranial nerve II	1
substantia nigra pars reticulata	1
deltoid	1
gluteal muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATPAF2	226	ubiquitous	marker	right testis, left testis, hindlimb stylopod muscle
MT-ATP6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, descending thoracic aorta
MT-ATP8	134		marker	gastrocnemius, right ovary, right lung
ATP5F1A	295	ubiquitous	marker	heart right ventricle, esophagus squamous epithelium, renal medulla
ATP5F1B	288	ubiquitous	marker	apex of heart, cardiac ventricle, heart left ventricle
ATP5F1D	292	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, mucosa of transverse colon
ATP5F1E	296	ubiquitous	marker	renal medulla, cranial nerve II, substantia nigra pars reticulata
TMEM70	290	ubiquitous	marker	vastus lateralis, deltoid, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 19.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP5F1B	6,304
ATP5F1A	6,160
ATP5F1D	3,748
MT-ATP6	2,869
ATPAF2	2,081
ATP5F1E	1,742
TMEM70	1,548
MT-ATP8	916

Intra-cohort edges

A	B	Sources
ATP5F1A	ATP5F1B	intact, string_interaction
ATP5F1A	ATP5F1D	string_interaction
ATP5F1A	ATP5F1E	string_interaction
ATP5F1A	ATPAF2	intact, string_interaction
ATP5F1B	ATP5F1D	string_interaction
ATP5F1B	ATP5F1E	string_interaction
ATP5F1B	ATPAF2	biogrid_interaction, intact, string_interaction
ATP5F1B	MT-ATP8	intact
ATP5F1D	ATP5F1E	intact, string_interaction
ATP5F1D	ATPAF2	string_interaction
ATP5F1D	MT-ATP8	intact
ATP5F1E	ATPAF2	string_interaction
ATP5F1E	TMEM70	string_interaction
ATPAF2	MT-ATP6	string_interaction
ATPAF2	MT-ATP8	string_interaction
ATPAF2	TMEM70	string_interaction
MT-ATP6	MT-ATP8	string_interaction
MT-ATP6	TMEM70	string_interaction
MT-ATP8	TMEM70	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-ATP6	P00846	10
MT-ATP8	P03928	10
ATP5F1D	P30049	10
ATP5F1E	P56381	10
ATP5F1A	P25705	9
ATP5F1B	P06576	9

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATPAF2	Q8N5M1	86.07
TMEM70	Q9BUB7	73.16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 8 evidence-associated genes (6 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of ATP by chemiosmotic coupling	6	571.0×	2e-16	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Cristae formation	6	346.1×	2e-15	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Mitochondrial biogenesis	6	167.9×	1e-13	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Aerobic respiration and respiratory electron transport	6	88.5×	6e-12	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Organelle biogenesis and maintenance	6	66.0×	3e-11	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Metabolism	6	11.6×	8e-07	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
Mitochondrial protein degradation	3	57.1×	2e-05	MT-ATP6, ATP5F1A, ATP5F1B
Protein localization	2	63.4×	6e-04	ATP5F1A, ATP5F1B
Mitochondrial protein import	2	56.0×	7e-04	ATP5F1A, ATP5F1B
Mitochondrial translation termination	2	36.6×	0.001	MT-ATP6, MT-ATP8
Metabolism of proteins	3	6.2×	0.010	MT-ATP6, ATP5F1A, ATP5F1B
Transcriptional activation of mitochondrial biogenesis	1	34.0×	0.029	ATP5F1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
proton motive force-driven ATP synthesis	6	601.9×	1e-15	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
proton motive force-driven mitochondrial ATP synthesis	6	197.5×	8e-13	MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E
mitochondrial proton-transporting ATP synthase complex assembly	3	789.9×	3e-08	ATPAF2, TMEM70, ATP5F1D
ATP biosynthetic process	2	247.8×	2e-04	ATP5F1A, ATP5F1B
positive regulation of blood vessel endothelial cell migration	2	98.0×	9e-04	ATP5F1A, ATP5F1B
proton transmembrane transport	2	78.0×	0.001	MT-ATP6, ATP5F1B
proton-transporting ATP synthase complex assembly	1	2106.5×	0.002	ATPAF2
negative regulation of cell adhesion involved in substrate-bound cell migration	1	526.6×	0.006	ATP5F1B
lipid metabolic process	2	22.9×	0.009	ATP5F1A, ATP5F1B
response to copper ion	1	191.5×	0.013	ATP5F1D
cellular response to interleukin-7	1	162.0×	0.014	ATP5F1B
response to hyperoxia	1	140.4×	0.015	MT-ATP6
cellular response to nitric oxide	1	117.0×	0.016	ATP5F1A
protein complex oligomerization	1	84.3×	0.020	TMEM70
regulation of intracellular pH	1	75.2×	0.020	ATP5F1B
response to muscle activity	1	72.6×	0.020	ATP5F1A
cellular response to dexamethasone stimulus	1	72.6×	0.020	ATP5F1A
negative regulation of endothelial cell proliferation	1	68.0×	0.020	ATP5F1A
mitochondrial respiratory chain complex I assembly	1	51.4×	0.025	TMEM70
generation of precursor metabolites and energy	1	43.0×	0.029	ATP5F1B
aerobic respiration	1	31.0×	0.038	ATP5F1D
response to ethanol	1	18.3×	0.061	ATP5F1A
protein homooligomerization	1	15.3×	0.067	TMEM70
osteoblast differentiation	1	15.2×	0.067	ATP5F1B
angiogenesis	1	7.8×	0.121	ATP5F1B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 6 of 8 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATPAF2	0	0
MT-ATP6	0	0
MT-ATP8	0	0
ATP5F1A	0	0
ATP5F1B	0	0
ATP5F1D	0	0
ATP5F1E	0	0
TMEM70	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATP5F1A	6	Binding:6
ATP5F1B	5	Binding:5
MT-ATP6	1	Binding:1
MT-ATP8	1	Binding:1
ATP5F1D	1	Binding:1
TMEM70	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	ATPAF2, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1E, TMEM70

Undrugged target profiles

8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ATPAF2	0	—
MT-ATP6	1	—
MT-ATP8	1	—
ATP5F1A	6	—
ATP5F1B	5	—
ATP5F1D	1	—
ATP5F1E	0	—
TMEM70	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.