ATP6V1B2

ATPase H+ transporting V1 subunit B2, the group of ATPase F1/V1 alpha/A and beta/B subunit family|V-type ATPase subunits

Basic information

Region (hg38): 8:20197381-20230399

Previous symbols: [ "VPP3", "ATP6B2" ]

Links

ENSG00000147416 ∙ NCBI:526 ∙ OMIM:606939 ∙ HGNC:854 ∙ Uniprot:P21281 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant deafness - onychodystrophy syndrome (Strong), mode of inheritance: AD
• Zimmermann-Laband syndrome (Supportive), mode of inheritance: AR
• autosomal dominant deafness - onychodystrophy syndrome (Supportive), mode of inheritance: AD
• DOORS syndrome (Supportive), 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
Deafness, congenital, with onychodystrophy, autosomal dominant; Zimmermann-Laband syndrome 2	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic	18541964; 23994350; 24913193; 25915598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP6V1B2 gene.

• ATP6V1B2 related neurodevelopmental disorders (1 variants)
• not provided (1 variants)
• Zimmermann-Laband syndrome 2 (1 variants)
• Autosomal dominant deafness - onychodystrophy syndrome (1 variants)
• Neurodevelopmental delay (1 variants)
• Zimmermann-Laband syndrome with epileptic encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6V1B2 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				9	2	11
missense	1	4	46	4	2	57
nonsense	2	1	2			5
start loss						0
frameshift			1			1
inframe indel		1	1		1	3
splice donor/acceptor (+/-2bp)			1			1
splice region				2	2	4
non coding				3	14	17
Total	3	6	51	16	19

Variants in ATP6V1B2

This is a list of pathogenic ClinVar variants found in the ATP6V1B2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-20197406-G-C		ATP6V1B2-related disorder	Likely benign (Nov 26, 2019)
8-20197413-C-A		Inborn genetic diseases	Likely benign (Mar 01, 2024)
8-20197417-G-A			Benign (Jun 01, 2024)
8-20197420-C-A		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
8-20197420-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2023)
8-20197420-CGATGCGGGG-C			Benign (Aug 01, 2024)
8-20197422-A-G		Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
8-20197425-C-T		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
8-20197429-G-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2024)
8-20197440-G-A		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
8-20197441-G-A		ATP6V1B2-related disorder	Uncertain significance (May 27, 2023)
8-20197443-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 01, 2023)
8-20197446-G-T			Benign (Dec 31, 2019)
8-20197449-C-G		Inborn genetic diseases	Likely benign (Aug 21, 2023)
8-20197449-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 21, 2022)
8-20197455-C-G			Uncertain significance (Aug 12, 2019)
8-20197530-C-A		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
8-20197530-C-T		Zimmermann-Laband syndrome 2	Likely pathogenic (Feb 17, 2023)
8-20204546-C-G			Benign/Likely benign (Jun 01, 2024)
8-20209328-A-G			Benign (May 16, 2021)
8-20209366-A-C			Benign (May 10, 2021)
8-20209442-T-C			Uncertain significance (Feb 02, 2022)
8-20209457-C-T		Inborn genetic diseases	Uncertain significance (May 10, 2021)
8-20209469-C-T		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
8-20209478-A-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP6V1B2	protein_coding	protein_coding	ENST00000276390	14	29453

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00846	125726	0	5	125731	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.49	172	291	0.590	0.0000157	3310
Missense in Polyphen		27	113.33	0.23824		1236
Synonymous	-1.05	121	107	1.13	0.00000613	1015
Loss of Function	4.58	4	31.9	0.125	0.00000209	323

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
• Disease: DISEASE: Zimmermann-Laband syndrome 2 (ZLS2) [MIM:616455]: A disorder characterized by gingival fibromatosis, dysplastic or absent nails, finger abnormalities, hepatosplenomegaly, and abnormalities of the cartilage of the nose and/or ears. {ECO:0000269|PubMed:25915598}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, congenital, with onychodystrophy, autosomal dominant (DDOD) [MIM:124480]: An autosomal dominant syndrome characterized mainly by congenital sensorineural hearing loss accompanied by dystrophic or absent nails. Coniform teeth, selective tooth agenesis, and hands and feet abnormalities are present in some patients. {ECO:0000269|PubMed:24913193}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.279

Intolerance Scores

• loftool: 0.146
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.33

Haploinsufficiency Scores

• pHI: 0.821
• hipred: Y
• hipred_score: 0.708
• ghis: 0.565

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.655

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp6v1b2
• Phenotype: hematopoietic system 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); immune system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;regulation of macroautophagy;transferrin transport;ion transmembrane transport;ATP metabolic process;proton transmembrane transport
• Cellular component: ruffle;lysosomal membrane;cytosol;plasma membrane;microvillus;endomembrane system;integral component of membrane;proton-transporting V-type ATPase, V1 domain;melanosome;myelin sheath;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: protein binding;ATP binding;proton transmembrane transporter activity;proton-transporting ATPase activity, rotational mechanism