ATP6AP2

ATPase H+ transporting accessory protein 2

Basic information

Region (hg38): X:40579371-40606848

Previous symbols: [ "ATP6IP2" ]

Links

ENSG00000182220 ∙ NCBI:10159 ∙ OMIM:300556 ∙ HGNC:18305 ∙ Uniprot:O75787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Hedera type (Limited), mode of inheritance: XLR
• X-linked parkinsonism-spasticity syndrome (Moderate), mode of inheritance: XL
• syndromic X-linked intellectual disability Hedera type (Moderate), mode of inheritance: XL
• congenital disorder of glycosylation, type IIr (Strong), mode of inheritance: AR
• X-linked parkinsonism-spasticity syndrome (Limited), mode of inheritance: XL
• syndromic X-linked intellectual disability Hedera type (Moderate), mode of inheritance: XL
• syndromic X-linked intellectual disability Hedera type (Supportive), mode of inheritance: XL
• X-linked parkinsonism-spasticity syndrome (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability Hedera type (Limited), mode of inheritance: XL
• congenital disorder of glycosylation, type IIr (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability Hedera type (Strong), mode of inheritance: XL
• X-linked parkinsonism-spasticity syndrome (Limited), mode of inheritance: Unknown
• ATP6AP2-related disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinsonism with spasticity, X-linked; Congenital disorder of glycosylation, type IIr	XL	Allergy/Immunology/Infectious; Hematologic; Neurologic	In Parkinsonism, response to l-dopa has been reported; In Congenital disorder of glycosylation, type IIr, individuals have been described with recurrent infections, and awareness may allow early diagnosis and early and aggressive treatment of infections; In Congenital disorder of glycosylation, type IIr, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	11782983; 15746149; 20629132; 23595882; 23871722
The evidence of variants being related to disease causation for some conditions has been questioned due to subsequent population-based studies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP6AP2 gene.

• Syndromic X-linked intellectual disability Hedera type (133 variants)
• not provided (71 variants)
• not specified (19 variants)
• Inborn genetic diseases (14 variants)
• Congenital disorder of glycosylation, type IIr (3 variants)
• Congenital disorder of glycosylation, type IIr;X-linked parkinsonism-spasticity syndrome;Syndromic X-linked intellectual disability Hedera type (2 variants)
• History of neurodevelopmental disorder (2 variants)
• X-linked parkinsonism-spasticity syndrome;Syndromic X-linked intellectual disability Hedera type (1 variants)
• ATP6AP2-related disorder (1 variants)
• See cases (1 variants)
• Syndromic X-linked intellectual disability Hedera type;Congenital disorder of glycosylation, type IIr;X-linked parkinsonism-spasticity syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6AP2 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	1		1	29	3	34
missense		1	77	2	2	82
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			8	6		14
non coding			3	31	18	52
Total	1	1	81	62	23

Variants in ATP6AP2

This is a list of pathogenic ClinVar variants found in the ATP6AP2 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-40580783-G-T			Likely benign (Jun 19, 2018)
X-40580818-A-T			Likely benign (Jun 19, 2018)
X-40580842-C-T			Likely benign (Jun 19, 2018)
X-40580909-T-C			Likely benign (Jun 19, 2018)
X-40580946-G-C			Likely benign (Jun 14, 2018)
X-40580996-C-T		not specified	Uncertain significance (Apr 26, 2022)
X-40581020-C-A		not specified	Benign (Sep 23, 2014)
X-40581030-C-T		not specified	Likely benign (Jan 19, 2016)
X-40581031-G-C		not specified	Benign (Feb 28, 2013)
X-40581071-T-A		Syndromic X-linked intellectual disability Hedera type	Likely benign (Aug 30, 2022)
X-40581084-C-T		not specified • Syndromic X-linked intellectual disability Hedera type	Conflicting classifications of pathogenicity (Jun 21, 2022)
X-40581098-G-A		Syndromic X-linked intellectual disability Hedera type	Uncertain significance (Dec 02, 2021)
X-40581100-C-T		Syndromic X-linked intellectual disability Hedera type	Uncertain significance (Jun 27, 2023)
X-40581107-G-A		Syndromic X-linked intellectual disability Hedera type	Uncertain significance (Aug 31, 2023)
X-40581114-G-A		Syndromic X-linked intellectual disability Hedera type	Likely benign (Sep 10, 2021)
X-40581117-G-A		Syndromic X-linked intellectual disability Hedera type	Likely benign (Apr 20, 2022)
X-40581119-C-G		Syndromic X-linked intellectual disability Hedera type	Likely benign (May 22, 2022)
X-40581120-G-A		Syndromic X-linked intellectual disability Hedera type	Likely benign (Jul 09, 2023)
X-40588704-T-TTTTG			Benign (Nov 14, 2019)
X-40588882-G-A			Likely benign (Jun 16, 2018)
X-40588973-G-A		Syndromic X-linked intellectual disability Hedera type	Likely benign (Jul 07, 2023)
X-40588981-T-C		not specified • Syndromic X-linked intellectual disability Hedera type • Syndromic X-linked intellectual disability Hedera type;Congenital disorder of glycosylation, type IIr;X-linked parkinsonism-spasticity syndrome • ATP6AP2-related disorder	Benign/Likely benign (Jan 30, 2024)
X-40588995-G-A		Syndromic X-linked intellectual disability Hedera type	Uncertain significance (Jul 14, 2021)
X-40588998-A-G		Syndromic X-linked intellectual disability Hedera type	Uncertain significance (Feb 08, 2022)
X-40588999-C-T		Syndromic X-linked intellectual disability Hedera type	Likely benign (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP6AP2	protein_coding	protein_coding	ENST00000378438	9	25744

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.871	0.129	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	84	139	0.603	0.0000108	2288
Missense in Polyphen		21	37.824	0.5552		724
Synonymous	0.689	43	49.1	0.875	0.00000365	695
Loss of Function	2.80	1	11.1	0.0903	7.70e-7	211

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a renin and prorenin cellular receptor. May mediate renin-dependent cellular responses by activating ERK1 and ERK2. By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, it may also play a role in the renin-angiotensin system (RAS). {ECO:0000269|PubMed:12045255}.
• Disease: DISEASE: Mental retardation, X-linked, with epilepsy (MRXE) [MIM:300423]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXE patients manifest mild to moderate mental retardation associated with epilepsy, delays in motor milestones and speech acquisition in infancy. {ECO:0000269|PubMed:15746149}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Parkinsonism with spasticity, X-linked (XPDS) [MIM:300911]: A syndrome characterized by parkinsonian features, such as cogwheel rigidity, resting tremor and bradykinesia, and variably penetrant spasticity. {ECO:0000269|PubMed:23595882}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;ACE Inhibitor Pathway;Oxidative phosphorylation;Neutrophil degranulation;Peptide hormone metabolism;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins;Innate Immune System;Immune System;Wnt signaling network (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.197
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.654
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp6ap2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; renal/urinary 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: atp6ap2
• Affected structure: enterocyte
• Phenotype tag: abnormal
• Phenotype quality: dilated

Gene ontology

• Biological process: angiotensin maturation;rostrocaudal neural tube patterning;positive regulation of Wnt signaling pathway;positive regulation of transforming growth factor beta1 production;neutrophil degranulation;regulation of MAPK cascade;eye pigmentation;head morphogenesis
• Cellular component: plasma membrane;external side of plasma membrane;integral component of membrane;neuron projection;cell body;extracellular exosome;tertiary granule membrane;ficolin-1-rich granule membrane
• Molecular function: protein binding;enzyme binding;signaling receptor activity