ATP11A

ATPase phospholipid transporting 11A, the group of ATPase phospholipid transporting

Basic information

Region (hg38): 13:112690037-112887168

Links

ENSG00000068650 ∙ NCBI:23250 ∙ OMIM:605868 ∙ HGNC:13552 ∙ Uniprot:P98196 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 24 (Limited), mode of inheritance: AD
• hearing loss, autosomal dominant 84 (Moderate), mode of inheritance: AD
• auditory neuropathy, autosomal dominant 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 84; Auditory neuropathy, autosomal dominant 2	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Neurologic	35278131; 34403372; 36300302
The onset of hearing loss in Deafness, autosomal dominant 84 has been described as variable; Leukodystrophy, hypomyelinating, 24 has been described as involving hypothyroidism, cataracts, and frequent infections in one described individual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP11A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP11A 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				13	10	23
missense			72	6	2	80
nonsense			1			1
start loss						0
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	3	1	6
non coding			7	5	5	17
Total	0	1	82	24	17

Variants in ATP11A

This is a list of pathogenic ClinVar variants found in the ATP11A region.

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

Position	Type	Phenotype	Significance	ClinVar
13-112690427-G-A		Hearing loss, autosomal dominant 84	Pathogenic (May 24, 2023)
13-112690441-C-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
13-112785175-A-G		Hearing loss, autosomal dominant 84	Uncertain significance (Mar 24, 2023)
13-112785203-C-T			Likely benign (May 01, 2023)
13-112785205-CA-TC		Leukodystrophy, hypomyelinating, 24	Uncertain significance (Aug 11, 2022)
13-112804971-CTTTAT-C		ATP11A-related disorder	Uncertain significance (Aug 21, 2023)
13-112805044-C-G		Leukodystrophy, hypomyelinating, 24	Pathogenic (May 16, 2023)
13-112805055-G-A			Benign (Jun 23, 2018)
13-112806245-A-G			Likely benign (Apr 28, 2018)
13-112810613-T-A			Benign/Likely benign (Jun 01, 2024)
13-112810641-A-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
13-112810679-T-C		ATP11A-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 19, 2023)
13-112810691-G-A		Inborn genetic diseases • ATP11A-related disorder	Conflicting classifications of pathogenicity (Mar 22, 2023)
13-112810692-G-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2021)
13-112810703-C-T		Inborn genetic diseases	Uncertain significance (May 04, 2023)
13-112810706-A-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
13-112810716-G-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
13-112816138-T-C		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
13-112816182-G-A		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
13-112819312-C-T			Likely benign (Jun 17, 2018)
13-112819355-G-A		Inborn genetic diseases	Uncertain significance (Feb 14, 2024)
13-112819406-A-G		not specified	Uncertain significance (Oct 20, 2023)
13-112823357-G-A			Likely benign (May 14, 2018)
13-112824360-G-A			Likely benign (Jul 29, 2018)
13-112824381-A-G			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP11A	protein_coding	protein_coding	ENST00000487903	29	196840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000405	1.00	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	592	693	0.854	0.0000437	7450
Missense in Polyphen		136	218.02	0.62381		2358
Synonymous	-1.13	324	299	1.08	0.0000232	2131
Loss of Function	5.19	23	69.8	0.330	0.00000359	768

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000899	0.000893
Ashkenazi Jewish	0.000444	0.000397
East Asian	0.000402	0.000381
Finnish	0.000291	0.000277
European (Non-Finnish)	0.000436	0.000413
Middle Eastern	0.000402	0.000381
South Asian	0.000603	0.000523
Other	0.000716	0.000652

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 (Probable). May be involved in the uptake of farnesyltransferase inhibitor drugs, such as lonafarnib. {ECO:0000269|PubMed:15860663, ECO:0000305}.
• Pathway: Lung fibrosis;Neutrophil degranulation;Ion channel transport;Innate Immune System;Immune System;Transport of small molecules;Ion transport by P-type ATPases (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.136
• rvis_EVS: -1.61
• rvis_percentile_EVS: 3.01

Haploinsufficiency Scores

• pHI: 0.221
• hipred: Y
• hipred_score: 0.605
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.171

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp11a
• Phenotype: vision/eye phenotype; limbs/digits/tail 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); skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo 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); growth/size/body region phenotype; hematopoietic system phenotype; 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); craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: neutrophil degranulation;phospholipid translocation
• Cellular component: lysosomal membrane;early endosome;endoplasmic reticulum;trans-Golgi network;plasma membrane;membrane;integral component of membrane;specific granule membrane;intracellular membrane-bounded organelle;recycling endosome;tertiary granule membrane
• Molecular function: magnesium ion binding;phospholipid-translocating ATPase activity;protein binding;ATP binding