ATP6AP1

ATPase H+ transporting accessory protein 1

Basic information

Region (hg38): X:154428633-154436516

Previous symbols: [ "ATP6S1", "ATP6IP1" ]

Links

ENSG00000071553 ∙ NCBI:537 ∙ OMIM:300197 ∙ HGNC:868 ∙ Uniprot:Q15904 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the ATP6AP1 gene.

• Immunodeficiency 47 (2 variants)
• not provided (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.

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			2	47	9	58
missense	1	2	73	5	14	95
nonsense			1			1
start loss			1			1
frameshift						0
inframe indel		2	9	3	1	15
splice donor/acceptor (+/-2bp)			1			1
splice region			5	7	2	14
non coding	1	1	2	25	10	39
Total	2	5	89	80	34

Variants in ATP6AP1

This is a list of pathogenic ClinVar variants found in the ATP6AP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-154428689-GGCTAT-G			Uncertain significance (Sep 27, 2022)
X-154428701-G-C			Likely benign (Jul 10, 2023)
X-154428703-C-A			Uncertain significance (Jan 15, 2023)
X-154428705-A-G			Uncertain significance (Apr 01, 2022)
X-154428710-G-T			Likely benign (Jul 05, 2022)
X-154428717-C-T			Uncertain significance (Jan 31, 2020)
X-154428721-T-A		ATP6AP1-related disorder	Uncertain significance (Nov 07, 2023)
X-154428727-T-G			Uncertain significance (Jun 11, 2023)
X-154428729-G-C			Uncertain significance (Jan 02, 2024)
X-154428735-C-T		ATP6AP1-related disorder	Conflicting classifications of pathogenicity (Jan 09, 2024)
X-154428737-G-A			Benign (Feb 01, 2024)
X-154428737-G-G			Benign (Feb 01, 2024)
X-154428757-G-T			Uncertain significance (Oct 28, 2022)
X-154428763-C-G			Uncertain significance (Oct 24, 2021)
X-154428764-G-A			Likely benign (Mar 02, 2023)
X-154428776-G-A			Likely benign (Jul 17, 2021)
X-154428787-TGGC-T		ATP6AP1-related disorder	Uncertain significance (Jan 03, 2024)
X-154428787-TGGCGGC-T			Uncertain significance (Jul 26, 2023)
X-154428787-TGGCGGCGGC-T			Uncertain significance (Jun 19, 2023)
X-154428787-T-TGGC		Inborn genetic diseases	Benign/Likely benign (Jan 04, 2024)
X-154428787-T-TGGCGGC		not specified • Inborn genetic diseases	Benign (Jan 30, 2024)
X-154428787-T-TGGCGGCGGC			Likely benign (Dec 25, 2023)
X-154428787-T-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC			Uncertain significance (Aug 19, 2022)
X-154428790-C-T			Benign (Jan 08, 2024)
X-154428790-C-CGGA			Likely benign (Oct 06, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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