ATP5F1E

ATP synthase F1 subunit epsilon, the group of Mitochondrial complex V: ATP synthase subunits

Basic information

Region (hg38): 20:59025475-59032345

Previous symbols: [ "ATP5E" ]

Links

ENSG00000124172 ∙ NCBI:514 ∙ OMIM:606153 ∙ HGNC:838 ∙ Uniprot:P56381 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial proton-transporting ATP synthase complex deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex V (ATP synthase) deficiency nuclear type 3 (Limited), mode of inheritance: AR
• mitochondrial complex V (ATP synthase) deficiency nuclear type 3 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3	AR	Audiologic/Otolaryngologic; Cardiovascular	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Cardiomyopathy has been described, and awareness may enable early diagnosis and management	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic	18953340; 20566710; 34954817

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP5F1E gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP5F1E 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				6		6
missense			9	1		10
nonsense			2			2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding				4	6	10
Total	0	0	12	11	6

Variants in ATP5F1E

This is a list of pathogenic ClinVar variants found in the ATP5F1E region.

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

Position	Type	Phenotype	Significance	ClinVar
20-59030311-C-A		Mitochondrial complex V (ATP synthase) deficiency nuclear type 3	Uncertain significance (Mar 29, 2024)
20-59030311-C-T			Uncertain significance (Jun 11, 2022)
20-59030315-C-T			Likely benign (May 26, 2023)
20-59030315-CTTT-C			Uncertain significance (Sep 29, 2022)
20-59030345-A-T			Likely benign (Apr 06, 2018)
20-59030346-G-C			Uncertain significance (Mar 19, 2023)
20-59030348-A-G			Likely benign (Apr 06, 2018)
20-59030376-G-T		ATP5F1E-related disorder	Likely benign (Jan 12, 2024)
20-59030377-T-C			Uncertain significance (Feb 11, 2023)
20-59030405-A-C			Uncertain significance (Dec 13, 2022)
20-59030408-G-C			Uncertain significance (Aug 27, 2023)
20-59030420-T-G		ATP5F1E-related disorder	Likely benign (Apr 24, 2019)
20-59030421-C-G			Uncertain significance (Oct 28, 2023)
20-59030422-G-A			Uncertain significance (Jun 03, 2023)
20-59030427-T-C		Mitochondrial complex V (ATP synthase) deficiency nuclear type 3	Pathogenic (Sep 01, 2010)
20-59030494-T-A			Likely benign (Jun 14, 2018)
20-59030592-C-T			Likely benign (Sep 11, 2018)
20-59031916-A-G			Benign (Jun 14, 2018)
20-59032205-G-A		not specified	Benign (Jan 18, 2024)
20-59032214-G-A			Uncertain significance (Dec 17, 2022)
20-59032215-C-A			Uncertain significance (Feb 09, 2023)
20-59032224-G-A			Uncertain significance (Aug 23, 2022)
20-59032229-G-A			Uncertain significance (Dec 28, 2023)
20-59032240-G-A			Likely benign (May 12, 2023)
20-59032241-T-G			Uncertain significance (Jun 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP5F1E	protein_coding	protein_coding	ENST00000243997	2	6916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00887	0.596	125739	0	7	125746	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.173	28	25.5	1.10	0.00000124	324
Missense in Polyphen		8	8.1902	0.97678		111
Synonymous	-0.424	11	9.35	1.18	4.98e-7	93
Loss of Function	0.262	3	3.53	0.850	2.34e-7	37

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000396	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000179	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(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits (By similarity). {ECO:0000250}.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Mitochondrial Electron Transport Chain;Electron Transport Chain;Oxidative phosphorylation;adenosine ribonucleotides <i>de novo</i> biosynthesis;Formation of ATP by chemiosmotic coupling;The citric acid (TCA) cycle and respiratory electron transport;Purine metabolism;Metabolism;superpathway of purine nucleotide salvage;Cristae formation;Mitochondrial biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.;purine nucleotides <i>de novo</i> biosynthesis;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.264
• hipred: N
• hipred_score: 0.386
• ghis: 0.433

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Atp5e
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: ATP biosynthetic process;cristae formation;mitochondrial ATP synthesis coupled proton transport;ATP hydrolysis coupled cation transmembrane transport
• Cellular component: mitochondrial proton-transporting ATP synthase complex, catalytic core F(1);mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;mitochondrial matrix
• Molecular function: ATPase activity;transmembrane transporter activity;proton-transporting ATP synthase activity, rotational mechanism