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): 3:113746770-113812056

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

developmental and epileptic encephalopathy 93 (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
developmental and epileptic encephalopathy 93 (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
developmental and epileptic encephalopathy 93 (Strong), mode of inheritance: AD
autosomal recessive cutis laxa type 2D (Strong), mode of inheritance: AR

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 (307 variants)
Inborn_genetic_diseases (39 variants)
Developmental_and_epileptic_encephalopathy_93 (38 variants)
ATP6V1A-related_disorder (14 variants)
Autosomal_recessive_cutis_laxa_type_2D (7 variants)
not_specified (5 variants)
Cerebral_visual_impairment_and_intellectual_disability (1 variants)
Vascular_disorder (1 variants)
Encephalopathy (1 variants)
Seizure (1 variants)
Neurodevelopmental_abnormality (1 variants)
Developmental_disorder (1 variants)
Developmental_and_epileptic_encephalopathy,_2 (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. These statistics are base on transcript: NM_000001690.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	79 clinvar	3 clinvar	86
missense	10 clinvar	13 clinvar	164 clinvar	4 clinvar	1 clinvar	192
nonsense			3 clinvar			3
start loss						0
frameshift			11 clinvar			11
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	10	13	184	83	4

Highest pathogenic variant AF is 0.0000068164

Loading clinvar variants...

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
Phenotype

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