ATP8A2

ATPase phospholipid transporting 8A2, the group of ATPase phospholipid transporting

Basic information

Region (hg38): 13:25371974-26025851

Links

ENSG00000132932 ∙ NCBI:51761 ∙ OMIM:605870 ∙ HGNC:13533 ∙ Uniprot:Q9NTI2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 (Limited), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium (Supportive), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	22892528

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP8A2 gene.

• Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 (7 variants)
• not provided (6 variants)
• Dysequilibrium syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP8A2 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	77	15	94
missense		2	166	5	1	174
nonsense	3	6	1			10
start loss						0
frameshift	8	4				12
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	10	1			14
splice region		2	11	18	3	34
non coding			3	60	21	84
Total	14	22	175	142	37

Highest pathogenic variant AF is 0.0000131

Variants in ATP8A2

This is a list of pathogenic ClinVar variants found in the ATP8A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-25372221-C-A			Uncertain significance (Aug 28, 2021)
13-25372223-G-C		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
13-25372236-C-G		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
13-25372242-T-A			Likely benign (Oct 27, 2023)
13-25372269-G-A			Likely benign (Jan 22, 2024)
13-25372278-C-T			Likely benign (Aug 17, 2022)
13-25372280-C-G		Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
13-25372281-G-C			Likely benign (Nov 10, 2023)
13-25372298-G-A		ATP8A2-related disorder	Conflicting classifications of pathogenicity (Jan 28, 2024)
13-25372300-G-GGGGCGCGGCGAGGGAGGGT			Benign (Jan 27, 2023)
13-25468959-T-G			Benign (Jan 14, 2024)
13-25468973-G-T			Likely benign (Nov 01, 2022)
13-25468975-A-G		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4	Pathogenic (Jun 26, 2018)
13-25468977-G-A			Likely benign (Jan 19, 2024)
13-25468996-G-C			Uncertain significance (Apr 01, 2022)
13-25469017-T-C			Likely benign (Jun 25, 2023)
13-25469029-GGC-G			Conflicting classifications of pathogenicity (Feb 17, 2022)
13-25469044-A-C		not specified	Benign (Jan 31, 2024)
13-25469045-G-T		not specified	Conflicting classifications of pathogenicity (Jul 17, 2015)
13-25469047-C-T			Likely benign (Sep 27, 2022)
13-25469058-C-T		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 • ATP8A2-related disorder	Conflicting classifications of pathogenicity (Jan 24, 2024)
13-25469065-C-A			Likely benign (Mar 20, 2022)
13-25469066-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
13-25469067-G-T			Uncertain significance (May 15, 2022)
13-25469073-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP8A2	protein_coding	protein_coding	ENST00000381655	37	653781

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.20e-12	1.00	124752	0	58	124810	0.000232

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.30	490	655	0.748	0.0000357	7721
Missense in Polyphen		163	268.7	0.60663		3366
Synonymous	0.614	240	252	0.951	0.0000151	2274
Loss of Function	4.39	33	73.7	0.448	0.00000370	883

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000303
Ashkenazi Jewish	0.0000998	0.0000993
East Asian	0.000390	0.000389
Finnish	0.0000933	0.0000928
European (Non-Finnish)	0.000302	0.000300
Middle Eastern	0.000390	0.000389
South Asian	0.000164	0.000163
Other	0.000170	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Involved in regulation of neurite outgrowth; acting in synergy with TMEM30A. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival.
• Disease: DISEASE: Note=A chromosomal aberration disrupting ATP8A2 has been found in a patient with severe mental retardation and major hypotonia. Translocation t(10;13)(p12.1;q12.13) (PubMed:20683487). {ECO:0000269|PubMed:20683487}.
• Pathway: Ion channel transport;Transport of small molecules;Ion transport by P-type ATPases (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.374
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.89

Haploinsufficiency Scores

• pHI: 0.332
• hipred: Y
• hipred_score: 0.693
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.282

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp8a2
• Phenotype: vision/eye 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; pigmentation 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: involuntary skeletal muscle contraction;axonogenesis;aging;negative regulation of cell population proliferation;retina layer formation;positive regulation of neuron projection development;response to auditory stimulus;positive regulation of multicellular organism growth;inner ear morphogenesis;eating behavior;skin development;phospholipid translocation;neuron development;neuromuscular process controlling posture;detection of light stimulus involved in visual perception;neurofilament cytoskeleton organization;positive regulation of phospholipid translocation
• Cellular component: photoreceptor outer segment;nucleoplasm;endosome;Golgi apparatus;plasma membrane;integral component of membrane
• Molecular function: magnesium ion binding;phospholipid-translocating ATPase activity;ATP binding