ATP6AP1
ATPase H+ transporting accessory protein 1
Basic information
Region (hg38): X:154428633-154436516
Previous symbols: [ "ATP6S1", "ATP6IP1" ]
Links
Phenotypes
GenCC
Source:
- immunodeficiency 47 (Strong), mode of inheritance: AR
- immunodeficiency 47 (Moderate), mode of inheritance: XL
- immunodeficiency 47 (Limited), mode of inheritance: XL
- immunodeficiency 47 (Strong), mode of inheritance: XL
- congenital disorder of glycosylation type II (Limited), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 47 | XL | Allergy/Immunology/Infectious | Among other features, individuals may have infantile-onset severe infections (and hypogammaglobulinemia) and awareness may allow preventive measures and early and aggressive treatment of infections | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Neurologic | 27231034; 29396028; 32058063; 32216104 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (261 variants)
- Immunodeficiency_47 (28 variants)
- Inborn_genetic_diseases (19 variants)
- ATP6AP1-related_disorder (9 variants)
- not_specified (6 variants)
- Decreased_total_neutrophil_count (1 variants)
- ALG2-congenital_disorder_of_glycosylation (1 variants)
- Intellectual_disability (1 variants)
- Decreased_total_lymphocyte_count (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6AP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001183.6. 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 | 16 | 65 | 89 | |||
| missense | 126 | 17 | 13 | 166 | ||
| nonsense | 6 | |||||
| start loss | 2 | 2 | ||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 18 | 18 | ||||
| Total | 5 | 5 | 170 | 82 | 21 |
Highest pathogenic variant AF is 0.000004957817
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ATP6AP1 | protein_coding | protein_coding | ENST00000369762 | 10 | 7885 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.991 | 0.00921 | 123422 | 0 | 1 | 123423 | 0.00000405 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.53 | 127 | 186 | 0.684 | 0.0000151 | 3019 |
| Missense in Polyphen | 44 | 79.593 | 0.55282 | 1264 | ||
| Synonymous | 0.221 | 80 | 82.5 | 0.969 | 0.00000699 | 985 |
| Loss of Function | 3.47 | 0 | 14.1 | 0.00 | 9.75e-7 | 225 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000125 | 0.00000903 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles. Guides the V-type ATPase into specialized subcellular compartments, such as neuroendocrine regulated secretory vesicles or the ruffled border of the osteoclast, thereby regulating its activity. Involved in membrane trafficking and Ca(2+)-dependent membrane fusion. May play a role in the assembly of the V-type ATPase complex. 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, ECO:0000305|PubMed:27231034}.;
- Disease
- DISEASE: Immunodeficiency 47 (IMD47) [MIM:300972]: A complex immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, defective glycosylation of serum proteins, and liver disease with neonatal jaundice and hepatosplenomegaly. Some patients may also have neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities. Inheritance is X-linked recessive. {ECO:0000269|PubMed:27231034}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Phagosome - Homo sapiens (human);Lysosome - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Oxidative phosphorylation;Signal Transduction;Transferrin endocytosis and recycling;Ion channel transport;Insulin receptor recycling;Signaling by Insulin receptor;Transport of small molecules;Iron uptake and transport;Signaling by Receptor Tyrosine Kinases
(Consensus)
Recessive Scores
- pRec
- 0.0867
Intolerance Scores
- loftool
- 0.0342
- rvis_EVS
- 0.44
- rvis_percentile_EVS
- 77.7
Haploinsufficiency Scores
- pHI
- 0.0751
- hipred
- Y
- hipred_score
- 0.518
- ghis
- 0.473
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.841
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Atp6ap1
- Phenotype
- embryo phenotype; 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); 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);
Zebrafish Information Network
- Gene name
- atp6ap1b
- Affected structure
- ciliated olfactory receptor neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased occurrence
Gene ontology
- Biological process
- cellular iron ion homeostasis;insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;regulation of cellular pH;transferrin transport;ion transmembrane transport;cellular response to increased oxygen levels;positive regulation of osteoblast differentiation;positive regulation of bone resorption;pH reduction;positive regulation of exocytosis;establishment of organelle localization;positive regulation of ERK1 and ERK2 cascade;proton transmembrane transport;positive regulation of osteoclast development
- Cellular component
- endoplasmic reticulum membrane;endosome membrane;integral component of membrane;proton-transporting two-sector ATPase complex;endoplasmic reticulum-Golgi intermediate compartment membrane;proton-transporting V-type ATPase, V1 domain;plasma membrane proton-transporting V-type ATPase complex;extracellular exosome
- Molecular function
- transporter activity;ATP binding;Rab GTPase binding;proton-transporting ATP synthase activity, rotational mechanism;proton-transporting ATPase activity, rotational mechanism