ATP6V1A

ATPase H+ transporting V1 subunit A, the group of ATPase F1/V1 alpha/A and beta/B subunit family|V-type ATPase subunits

Basic information

Region (hg38): 3:113746769-113812056

Previous symbols: [ "VPP2", "ATP6A1", "ATP6V1A1" ]

Links

ENSG00000114573 ∙ NCBI:523 ∙ OMIM:607027 ∙ HGNC:851 ∙ Uniprot:P38606 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epileptic encephalopathy, infantile or early childhood, 3 (Definitive), mode of inheritance: AD
• autosomal recessive cutis laxa type 2D (Moderate), mode of inheritance: AR
• autosomal recessive cutis laxa type 2D (Strong), mode of inheritance: AR
• autosomal recessive cutis laxa type 2D (Limited), mode of inheritance: AR
• epileptic encephalopathy, infantile or early childhood, 3 (Moderate), mode of inheritance: AD
• autosomal recessive cutis laxa type 2, classic type (Supportive), mode of inheritance: AR
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• autosomal recessive cutis laxa type 2D (Strong), mode of inheritance: AR
• epileptic encephalopathy, infantile or early childhood, 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cutis laxa, autosomal recessive, type IID	AR	Cardiovascular	The condition can include early-onset cardiomyopathy, and awareness may allow early diagnosis and management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	24459010; 28065471; 29668857

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP6V1A gene.

• not provided (176 variants)
• Epileptic encephalopathy, infantile or early childhood, 3 (15 variants)
• Inborn genetic diseases (11 variants)
• Autosomal recessive cutis laxa type 2D (3 variants)
• ATP6V1A-related condition (3 variants)
• not specified (2 variants)
• Epileptic encephalopathy, infantile or early childhood, 3;Autosomal recessive cutis laxa type 2D (2 variants)
• Encephalopathy (1 variants)
• Developmental and epileptic encephalopathy, 2 (1 variants)
• Developmental disorder (1 variants)
• Cerebral visual impairment and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6V1A 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	41	5	47
missense	3	8	85	1	1	98
nonsense			2			2
start loss						0
frameshift			4			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			3	6	1	10
non coding				26	16	42
Total	3	8	94	68	22

Variants in ATP6V1A

This is a list of pathogenic ClinVar variants found in the ATP6V1A region.

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

Position	Type	Phenotype	Significance	ClinVar
3-113778539-C-G			Benign (May 10, 2021)
3-113778660-A-G			Benign (May 10, 2021)
3-113778782-T-G			Uncertain significance (Sep 04, 2023)
3-113778783-C-T			Likely benign (Dec 19, 2023)
3-113778784-G-A			Uncertain significance (May 16, 2022)
3-113778784-G-T		Epileptic encephalopathy, infantile or early childhood, 3	Uncertain significance (Jan 25, 2023)
3-113778801-C-T			Likely benign (Aug 01, 2020)
3-113778809-G-C			Uncertain significance (Mar 31, 2023)
3-113778818-A-G		Inborn genetic diseases	Uncertain significance (May 18, 2023)
3-113778822-G-A			Likely benign (Sep 23, 2023)
3-113778833-C-G		Epileptic encephalopathy, infantile or early childhood, 3 • Inborn genetic diseases	Pathogenic/Likely pathogenic (Mar 22, 2023)
3-113778840-G-GTAA			Likely benign (Jul 12, 2023)
3-113780886-A-G			Benign (May 10, 2021)
3-113781044-C-A			Likely benign (Jun 24, 2023)
3-113781055-A-G			Uncertain significance (Sep 01, 2020)
3-113781067-A-G			Uncertain significance (Jul 10, 2023)
3-113781071-C-T			Uncertain significance (May 29, 2023)
3-113781072-G-A			Likely benign (Sep 23, 2022)
3-113781084-G-A		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
3-113781093-G-A			Uncertain significance (Mar 07, 2023)
3-113781108-C-T			Likely benign (Apr 30, 2023)
3-113781112-G-A			Uncertain significance (Mar 11, 2022)
3-113781124-G-A			Uncertain significance (Nov 15, 2022)
3-113781135-A-G			Likely benign (Sep 01, 2022)
3-113781149-T-C			Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP6V1A	protein_coding	protein_coding	ENST00000273398	14	65038

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.868	0.132	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.37	174	352	0.494	0.0000186	4039
Missense in Polyphen		29	136.16	0.21298		1574
Synonymous	0.214	112	115	0.975	0.00000582	1193
Loss of Function	4.36	6	33.0	0.182	0.00000192	378

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000269|PubMed:28296633}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Synaptic vesicle cycle - Homo sapiens (human);Phagosome - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Collecting duct acid secretion - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Signal Transduction;Transferrin endocytosis and recycling;Ion channel transport;adenosine ribonucleotides <i>de novo</i> biosynthesis;Insulin receptor recycling;Signaling by Insulin receptor;ROS, RNS production in phagocytes;Purine metabolism;Innate Immune System;Immune System;Transport of small molecules;superpathway of purine nucleotide salvage;Iron uptake and transport;Signaling by Receptor Tyrosine Kinases;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.237

Intolerance Scores

• loftool: 0.221
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.259
• hipred: Y
• hipred_score: 0.698
• ghis: 0.677

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.109

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Atp6v1a

Zebrafish Information Network

• Gene name: atp6v1aa
• Affected structure: vH ionocyte
• Phenotype tag: abnormal
• Phenotype quality: flux

Gene ontology

• Biological process: cellular iron ion homeostasis;insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;regulation of macroautophagy;transferrin transport;ion transmembrane transport;cellular response to increased oxygen levels;ATP metabolic process
• Cellular component: lysosomal membrane;vacuolar membrane;cytosol;plasma membrane;microvillus;apical plasma membrane;proton-transporting two-sector ATPase complex;proton-transporting V-type ATPase, V1 domain;myelin sheath;extracellular exosome
• Molecular function: ATP binding;proton-transporting ATPase activity, rotational mechanism