ATP5PO

ATP synthase peripheral stalk subunit OSCP, the group of Mitochondrial complex V: ATP synthase subunits

Basic information

Region (hg38): 21:33903453-33915814

Previous symbols: [ "ATP5O" ]

Links

ENSG00000241837 ∙ NCBI:539 ∙ OMIM:600828 ∙ HGNC:850 ∙ Uniprot:P48047 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7	AR	Cardiovascular	The condition can include hypertrophic cardiomyopathy, and early diagnosis may enable management	Biochemical; Cardiovascular; Craniofacial; Neurologic	34954817; 35621276

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP5PO gene.

• Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7 (2 variants)
• Severe global developmental delay;Dysphagia;Seizure;Microcephaly (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP5PO gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			12	1		13
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1				1
non coding	1					1
Total	2	0	12	1	1

Variants in ATP5PO

This is a list of pathogenic ClinVar variants found in the ATP5PO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-33903603-T-C		ATP5PO-related disorder	Likely benign (Jun 06, 2023)
21-33903617-C-G		not specified	Uncertain significance (Sep 29, 2023)
21-33903945-A-G		not specified	Uncertain significance (Nov 19, 2022)
21-33904003-G-C		not specified	Uncertain significance (Jun 05, 2024)
21-33907375-C-T		not specified	Uncertain significance (Aug 16, 2022)
21-33907473-T-C		Severe global developmental delay;Dysphagia;Seizure;Microcephaly • Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7	Pathogenic (Dec 22, 2021)
21-33909089-A-G			Benign (Feb 11, 2022)
21-33909096-G-A		not specified	Uncertain significance (May 08, 2023)
21-33909156-C-A		not specified	Uncertain significance (Dec 22, 2023)
21-33909168-G-A		not specified	Uncertain significance (Feb 23, 2023)
21-33914447-T-C		ATP5PO-related disorder • Leigh syndrome • Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7	Pathogenic/Likely pathogenic (Aug 09, 2020)
21-33914463-G-C		not specified	Uncertain significance (Mar 22, 2023)
21-33914467-A-G		not specified	Uncertain significance (Mar 28, 2023)
21-33914499-A-G		not specified	Uncertain significance (Nov 08, 2022)
21-33915730-G-A		Severe global developmental delay;Dysphagia;Seizure;Microcephaly • Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7	Pathogenic (Dec 22, 2021)
21-33915744-G-C		not specified	Uncertain significance (Feb 05, 2024)
21-33915745-A-G		not specified	Uncertain significance (Nov 09, 2021)
21-33915757-C-A		not specified	Uncertain significance (Oct 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP5PO	protein_coding	protein_coding	ENST00000290299	7	12528

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0581	0.926	125738	0	9	125747	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0269	117	118	0.993	0.00000640	1347
Missense in Polyphen		18	25.107	0.71693		364
Synonymous	-0.479	48	44.0	1.09	0.00000233	433
Loss of Function	2.10	4	11.8	0.339	6.47e-7	139

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) 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. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a 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. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Oxidative phosphorylation;Formation of ATP by chemiosmotic coupling;The citric acid (TCA) cycle and respiratory electron transport;Purine metabolism;Metabolism;Cristae formation;Mitochondrial biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.300

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.0813
• hipred: Y
• hipred_score: 0.519
• ghis: 0.549

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Atp5o

Zebrafish Information Network

• Gene name: atp5po
• Affected structure: anatomical system
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: ATP biosynthetic process;cristae formation;mitochondrial ATP synthesis coupled proton transport;ATP hydrolysis coupled cation transmembrane transport;proton transmembrane transport
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;plasma membrane
• Molecular function: transporter activity;protein binding;drug binding;ATPase activity;transmembrane transporter activity;proton-transporting ATP synthase activity, rotational mechanism