ATP5MC3

ATP synthase membrane subunit c locus 3, the group of Mitochondrial complex V: ATP synthase subunits

Basic information

Region (hg38): 2:175176258-175181710

Previous symbols: [ "ATP5G3" ]

Links

ENSG00000154518 ∙ NCBI:518 ∙ OMIM:602736 ∙ HGNC:843 ∙ Uniprot:P48201 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dystonia, early-onset, and/or spastic paraplegia (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia, early-onset, and/or spastic paraplegia	AD	Neurologic	Bilateral pallidal deep brain stimulation has been described as beneficial for ambulation and hand use	Neurologic	19006192; 34636445

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP5MC3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP5MC3 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		1	8	3		12
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	9	3	2

Variants in ATP5MC3

This is a list of pathogenic ClinVar variants found in the ATP5MC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-175178369-A-G			Benign (-)
2-175178398-G-C		Dystonia, early-onset, and/or spastic paraplegia	Pathogenic (May 04, 2023)
2-175178399-G-C		ATP5G3-associated disorder • Dystonia, early-onset, and/or spastic paraplegia	Likely pathogenic (Nov 28, 2019)
2-175179106-C-G			Uncertain significance (Dec 30, 2022)
2-175179135-C-A		Dystonia, early-onset, and/or spastic paraplegia	Pathogenic (May 04, 2023)
2-175179178-T-C		Inborn genetic diseases	Likely benign (May 01, 2023)
2-175179201-T-C		Inborn genetic diseases	Likely benign (Dec 13, 2022)
2-175179210-T-C		Inborn genetic diseases	Uncertain significance (Jan 18, 2023)
2-175179234-T-C		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
2-175179243-G-A		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
2-175179243-G-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
2-175180088-C-T			Benign (Feb 09, 2018)
2-175180121-G-C		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
2-175180135-G-A		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
2-175180161-T-C			Benign (Jan 25, 2018)
2-175180171-G-A		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
2-175181355-CAG-C			Uncertain significance (Apr 09, 2022)
2-175181363-G-C		Inborn genetic diseases	Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP5MC3	protein_coding	protein_coding	ENST00000284727	4	8350

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.257	0.718	125158	0	8	125166	0.0000320

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	51	76.0	0.671	0.00000354	893
Missense in Polyphen		13	29.313	0.44349		362
Synonymous	-0.489	32	28.7	1.12	0.00000141	303
Loss of Function	1.89	2	7.62	0.262	4.74e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000294	0.0000294
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.0000548	0.0000529
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.
• 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: 0.104

Intolerance Scores

• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.223
• hipred: Y
• hipred_score: 0.656
• ghis: 0.609

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Atp5g3

Gene ontology

• Biological process: ATP biosynthetic process;ATP synthesis coupled proton transport;ATP hydrolysis coupled proton transport;cristae formation
• Cellular component: mitochondrial proton-transporting ATP synthase complex, coupling factor F(o);mitochondrial outer membrane;mitochondrial proton-transporting ATP synthase complex;integral component of membrane;proton-transporting ATP synthase complex, coupling factor F(o)
• Molecular function: transporter activity;lipid binding;proton-transporting ATP synthase activity, rotational mechanism