ATP6V1B1

ATPase H+ transporting V1 subunit B1, the group of V-type ATPase subunits|ATPase F1/V1 alpha/A and beta/B subunit family

Basic information

Region (hg38): 2:70935900-70965431

Previous symbols: [ "VPP3", "ATP6B1" ]

Links

ENSG00000116039 ∙ NCBI:525 ∙ OMIM:192132 ∙ HGNC:853 ∙ Uniprot:P15313 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive distal renal tubular acidosis (Supportive), mode of inheritance: AR
• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (Definitive), mode of inheritance: AR
• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (Strong), mode of inheritance: AR
• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (Definitive), mode of inheritance: AR
• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (Strong), mode of inheritance: AR
• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss	AR	Renal	Individuals can present in infancy with acute with dehydration (which can be lethal), which can be prevented by early recognition	Audiologic/Otolaryngologic; Renal	9916796; 12414817; 12566520; 16433694; 18798332

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP6V1B1 gene.

• not_provided (593 variants)
• Renal_tubular_acidosis_with_progressive_nerve_deafness (267 variants)
• Inborn_genetic_diseases (75 variants)
• not_specified (42 variants)
• ATP6V1B1-related_disorder (22 variants)
• Distal_renal_tubular_acidosis (3 variants)
• Nephrocalcinosis (2 variants)
• Hearing_impairment (2 variants)
• Renal_tubular_acidosis (2 variants)
• Rare_genetic_deafness (1 variants)
• Renal_tubular_acidosis,_distal,_3,_with_or_without_sensorineural_hearing_loss (1 variants)
• Nephrolithiasis (1 variants)
• Abnormality_of_the_genitourinary_system (1 variants)
• Polydactyly,_postaxial,_type_A1 (1 variants)
• Usher_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6V1B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001692.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		3	14	227	3	247
missense	1	11	213	6	1	232
nonsense	16	11	2			29
start loss			3			3
frameshift	33	12				45
splice donor/acceptor (+/-2bp)	6	22			1	29
Total	56	59	232	233	5

Highest pathogenic variant AF is 0.000102152

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP6V1B1	protein_coding	protein_coding	ENST00000234396	14	29525

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.40e-9	0.890	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.232	297	308	0.963	0.0000199	3344
Missense in Polyphen		108	124.02	0.87085		1300
Synonymous	0.373	121	126	0.958	0.00000875	1025
Loss of Function	1.77	18	28.2	0.639	0.00000170	291

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000423	0.000423
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000272	0.000272
South Asian	0.000294	0.000294
Other	0.000327	0.000326

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: Renal tubular acidosis, distal, with progressive nerve deafness (dRTA-D) [MIM:267300]: An autosomal recessive disease characterized by the association of renal distal tubular acidosis with sensorineural hearing loss. Distal renal tubular acidosis is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha- intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. {ECO:0000269|PubMed:12414817, ECO:0000269|PubMed:12579397, ECO:0000269|PubMed:9916796}. 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;Insulin receptor recycling;Signaling by Insulin receptor;ROS, RNS production in phagocytes;Purine metabolism;Innate Immune System;Immune System;Transport of small molecules;Iron uptake and transport;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.324

Intolerance Scores

• loftool: 0.264
• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.75

Haploinsufficiency Scores

• pHI: 0.166
• hipred: Y
• hipred_score: 0.578
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.692

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp6v1b1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; skeleton phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; taste/olfaction phenotype

Gene ontology

• Biological process: ossification;regulation of pH;excretion;sensory perception of sound;insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;regulation of macroautophagy;transferrin transport;ion transmembrane transport;inner ear morphogenesis;pH reduction;ATP metabolic process;calcium ion homeostasis;proton transmembrane transport
• Cellular component: cytoplasm;cytosol;microvillus;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane;vacuolar proton-transporting V-type ATPase complex;proton-transporting V-type ATPase, V1 domain;extracellular exosome;extrinsic component of synaptic vesicle membrane
• Molecular function: ATP binding;proton transmembrane transporter activity;hydrolase activity;protein-containing complex binding