ATP8A2 (ATPase phospholipid transporting 8A2)

Gene

• Entrez ID: 51761
• Gene name: ATPase phospholipid transporting 8A2
• Gene symbol: ATP8A2
• Synonyms (NCBI Gene): ATP, ATPIB, CAMRQ4, IB, ML-1
• Chromosome: 13
• Chromosome location: 13q12.13
• Summary: The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs202017613	G>A	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs546968533	C>G,T	Pathogenic	Synonymous variant, missense variant, coding sequence variant
rs755133567	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs864309608	G>T	Uncertain-significance, likely-pathogenic	Genic upstream transcript variant, upstream transcript variant, coding sequence variant, missense variant
rs1064793377	G>A,T	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs1064795308	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064795309	AATGGT>-	Likely-pathogenic	5 prime UTR variant, intron variant, splice donor variant, genic upstream transcript variant, coding sequence variant
rs1064795610	C>T	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, 5 prime UTR variant, stop gained
rs1156904586	->T	Pathogenic, likely-pathogenic	Coding sequence variant, frameshift variant
rs1304109530	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1555263787	G>A	Likely-pathogenic	Genic downstream transcript variant, splice donor variant
rs1593326999	G>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant
rs1593410369	A>G	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, intron variant, missense variant
rs1593576872	T>A	Likely-pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028669	hsa-miR-30a-5p	Proteomics	18668040
MIRT032045	hsa-miR-16-5p	Proteomics	18668040
MIRT809720	hsa-miR-1236	CLIP-seq
MIRT809721	hsa-miR-3681	CLIP-seq
MIRT809722	hsa-miR-3691-5p	CLIP-seq
MIRT809723	hsa-miR-4432	CLIP-seq
MIRT809724	hsa-miR-4685-5p	CLIP-seq
MIRT809725	hsa-miR-4711-5p	CLIP-seq
MIRT809726	hsa-miR-4761-3p	CLIP-seq
MIRT809727	hsa-miR-576-5p	CLIP-seq
MIRT809728	hsa-miR-7	CLIP-seq
MIRT1939214	hsa-miR-4641	CLIP-seq
MIRT1939215	hsa-miR-4665-3p	CLIP-seq
MIRT1939216	hsa-miR-4760-3p	CLIP-seq
MIRT1939217	hsa-miR-604	CLIP-seq
MIRT1939218	hsa-miR-647	CLIP-seq
MIRT2178330	hsa-miR-1286	CLIP-seq
MIRT2178331	hsa-miR-2392	CLIP-seq
MIRT2178332	hsa-miR-3151	CLIP-seq
MIRT2178333	hsa-miR-3169	CLIP-seq
MIRT2178334	hsa-miR-3194-3p	CLIP-seq
MIRT2178335	hsa-miR-329	CLIP-seq
MIRT2178336	hsa-miR-345	CLIP-seq
MIRT2178337	hsa-miR-362-3p	CLIP-seq
MIRT2178338	hsa-miR-3941	CLIP-seq
MIRT2178339	hsa-miR-4275	CLIP-seq
MIRT809723	hsa-miR-4432	CLIP-seq
MIRT2178340	hsa-miR-4447	CLIP-seq
MIRT2178341	hsa-miR-4462	CLIP-seq
MIRT2178342	hsa-miR-4472	CLIP-seq
MIRT2178343	hsa-miR-4515	CLIP-seq
MIRT2178344	hsa-miR-4522	CLIP-seq
MIRT2178345	hsa-miR-466	CLIP-seq
MIRT2178346	hsa-miR-4672	CLIP-seq
MIRT2178347	hsa-miR-4698	CLIP-seq
MIRT2178348	hsa-miR-4766-5p	CLIP-seq
MIRT2178349	hsa-miR-491-5p	CLIP-seq
MIRT2178350	hsa-miR-495	CLIP-seq
MIRT2178351	hsa-miR-518d-5p	CLIP-seq
MIRT2178352	hsa-miR-519b-5p	CLIP-seq
MIRT2178353	hsa-miR-519c-5p	CLIP-seq
MIRT2178354	hsa-miR-520c-5p	CLIP-seq
MIRT2178355	hsa-miR-526a	CLIP-seq
MIRT2178356	hsa-miR-603	CLIP-seq
MIRT2178357	hsa-miR-610	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IEA
GO:0003011	Process	Involuntary skeletal muscle contraction	IEA
GO:0005515	Function	Protein binding	IPI	31397519
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005768	Component	Endosome	IEA
GO:0005794	Component	Golgi apparatus	IDA	20947505
GO:0005794	Component	Golgi apparatus	IEA
GO:0005802	Component	Trans-Golgi network	IBA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	20947505, 26567335
GO:0005886	Component	Plasma membrane	IEA
GO:0006869	Process	Lipid transport	IEA
GO:0007409	Process	Axonogenesis	IEA
GO:0008285	Process	Negative regulation of cell population proliferation	TAS	10551800
GO:0008340	Process	Determination of adult lifespan	IEA
GO:0010008	Component	Endosome membrane	IEA
GO:0010842	Process	Retina layer formation	IEA
GO:0010976	Process	Positive regulation of neuron projection development	IEA
GO:0010996	Process	Response to auditory stimulus	IEA
GO:0012505	Component	Endomembrane system	IEA
GO:0015247	Function	Aminophospholipid flippase activity	IEA
GO:0015914	Process	Phospholipid transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0040018	Process	Positive regulation of multicellular organism growth	IEA
GO:0042472	Process	Inner ear morphogenesis	IEA
GO:0042755	Process	Eating behavior	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043588	Process	Skin development	IEA
GO:0045332	Process	Phospholipid translocation	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0048666	Process	Neuron development	IBA
GO:0048666	Process	Neuron development	IEA
GO:0050884	Process	Neuromuscular process controlling posture	IEA
GO:0050908	Process	Detection of light stimulus involved in visual perception	IEA
GO:0060052	Process	Neurofilament cytoskeleton organization	IEA
GO:0061092	Process	Positive regulation of phospholipid translocation	IEA
GO:0090555	Function	Phosphatidylethanolamine flippase activity	ISS
GO:0090556	Function	Phosphatidylserine floppase activity	IEA
GO:0140326	Function	ATPase-coupled intramembrane lipid transporter activity	IBA
GO:0140326	Function	ATPase-coupled intramembrane lipid transporter activity	IEA
GO:0140331	Process	Aminophospholipid translocation	ISS
GO:0140346	Function	Phosphatidylserine flippase activity	ISS
GO:1990531	Component	Phospholipid-translocating ATPase complex	IEA
GO:1990531	Component	Phospholipid-translocating ATPase complex	IPI	20947505

Other IDs

• MIM: 605870
• HGNC: 13533
• e!Ensembl: ENSG00000132932

Protein

• UniProt ID: Q9NTI2
• Protein name: Phospholipid-transporting ATPase IB (EC 7.6.2.1) (ATPase class I type 8A member 2) (ML-1) (P4-ATPase flippase complex alpha subunit ATP8A2)
• Protein 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 distribut
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16209	PhoLip_ATPase_N	58 → 121	Phospholipid-translocating ATPase N-terminal	Family
  PF00122	E1-E2_ATPase	148 → 387		Family
  PF13246	Cation_ATPase	504 → 604		Family
  PF16212	PhoLip_ATPase_C	847 → 1099	Phospholipid-translocating P-type ATPase C-terminal	Family

• Tissue specificity: TISSUE SPECIFICITY: Strongly expressed in the brain, cerebellum, retina and testis. {ECO:0000269|PubMed:20683487, ECO:0000269|PubMed:22892528}.
• Sequence:

  MLNGAGLDKALKMSLPRRSRIRSSVGPVRSSLGYKKAEDEMSRATSVGDQLEAPARTIYL
  NQPHLNKFRDNQISTAKYSVLTFLPRFLYEQIRRAANAFFLFIALLQQIPDVSPTGRYTT
  LVPLIIILTIAGIKEIVEDFKRHKADNAVNKKKTIVLRNGMWHTIMWKEVAVGDIVKVVN
  GQYLPADVVLLSSSEPQAMCYVETANLDGETNLKIRQGLSHTADMQTREVLMKLSGTIEC
  EGPNRHLYDFTGNLNLDGKSLVALGPDQILLRGTQLRNTQWVFGIVVYTGHDTKLMQNST
  KAPLKRSNVEKVTNVQILVLFGILLVMALVSSAGALYWNRSHGEKNWYIKKMDTTSDNFG
  YNLLTFIILYNNLIPISLLVTLEVVKYTQALFINWDTDMYYIGNDTPAMARTSNLNEELG
  QVKYLFSDKTGTLTCNIMNFKKCSIAGVTYGHFPELAREPSSDDFCRMPPPCSDSCDFDD
  PRLLKNIEDRHPTAPCIQEFLTLLAVCHTVVPEKDGDNIIYQASSPDEAALVKGAKKLGF
  VFTARTPFSVIIEAMGQEQTFGILNVLEFSSDRKRMSVIVRTPSGRLRLYCKGADNVIFE
  RLSKDSKYMEETLCHLEYFATEGLRTLCVAYADLSENEYEEWLKVYQEASTILKDRAQRL
  EECYEIIEKNLLLLGATAIEDRLQAGVPETIATLLKAEIKIWVLTGDKQETAINIGYSCR
  LVSQNMALILLKEDSLDATRAAITQHCTDLGNLLGKENDVALIIDGHTLKYALSFEVRRS
  FLDLALSCKAVICCRVSPLQKSEIVDVVKKRVKAITLAIGDGANDVGMIQTAHVGVGISG
  NEGMQATNNSDYAIAQFSYLEKLLLVHGAWSYNRVTKCILYCFYKNVVLYIIELWFAFVN
  GFSGQILFERWCIGLYNVIFTALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKV
  FWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVTVCLKAGLET
  TAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPT
  ACLIEDVAWRAAKHTCKKTLLEEVQELETKSRVLGKAVLRDSNGKRLNERDRLIKRLGRK
  TPPTLFRGSSLQQGVPHGYAFSQEEHGAVSQEEVIRAYDTTKKKSRKK

• Sequence length: 1188

Pathways

KEGG:

Efferocytosis

Reactome:

Ion transport by P-type ATPases

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
ATP8A2-related disorder	Likely pathogenic; Pathogenic	rs1156904586	RCV003411475
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4	Likely pathogenic; Pathogenic	rs1566306570, rs763272441, rs373909734, rs2138177530, rs779337270, rs2137911082, rs2137994737, rs2038343394, rs1566188424, rs2542384306, rs1593531290, rs2542426988, rs2542315282, rs2542384109, rs1064793377, rs1085307694, rs755133567, rs1156904586, rs546968533, rs1304109530, rs1593410369, rs1593576872, rs1593326999, rs2039720333, rs267603791, rs2035763126, rs1304832284, rs2038491713	RCV001330940 RCV001330941 RCV001336352 RCV001780668 RCV001780669 RCV001780686 RCV002052049 RCV002052225 RCV002470105 RCV003136903 RCV003153119 RCV003397171 RCV004577188 RCV004586223 RCV003989534 RCV005869508 RCV002227478 RCV000988969 RCV000043652 RCV000985122 RCV000985123 RCV000984487 RCV000988970 RCV001250920 RCV003990879 RCV001195731 RCV001197115 RCV001254119
Dysequilibrium syndrome	Pathogenic	rs1952385477	RCV001034613

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Colon adenocarcinoma	Conflicting classifications of pathogenicity	rs202073376	RCV005901422
Epilepsy	Uncertain significance	rs1057518996	RCV000414852
Familial cancer of breast	Benign	rs2274135	RCV005914336
Lung cancer	Uncertain significance	rs372419009	RCV005928602
Severe intellectual deficiency	Uncertain significance	rs1057518996	RCV000414852
Uterine carcinosarcoma	Benign	rs2274135	RCV005914337
Uveal melanoma	Benign	rs199807614	RCV005927860

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma of Lung	Associate	28178989, 33029490
Alcohol Related Disorders	Associate	31612321
Ataxia	Associate	31612321
Brain Diseases	Associate	31612321
Brugada Syndrome	Associate	22056721
Carcinogenesis	Associate	28069692
Cerebellar Ataxia	Associate	31612321, 33079427
Cerebellar Diseases	Associate	22892528
Chorea	Associate	30012219
Choreoathetosis Hypothyroidism And Neonatal Respiratory Distress	Associate	30012219
Cognition Disorders	Associate	30012219
Colorectal Neoplasms	Associate	28502252
Congenital Hyperinsulinism	Associate	25931474
Developmental Disabilities	Associate	30012219, 35321980, 38436085
Dysequilibrium syndrome	Associate	33079427, 35321980, 38109455, 38436085
Dyskinesia Drug Induced	Associate	30012219
Dystonia	Associate	30012219
Early Onset Glaucoma	Associate	22056721, 34281161
Feeding and Eating Disorders	Associate	23568457
Genetic Diseases Inborn	Associate	38436085
Glioblastoma	Associate	31905754
Hearing Disorders	Associate	35321980
Hydrocephalus	Associate	38109455
Hyperkinesis	Associate	30012219
Inclusion Body Myopathy With Early Onset Paget Disease And Frontotemporal Dementia	Associate	28512218
Inflammation	Associate	27034593
Intellectual Disability	Associate	22892528, 33079427, 35321980
Leukemia Lymphocytic Chronic B Cell	Associate	15972634
Methylmalonic acidemia	Associate	20556797, 34757128
Movement Disorders	Associate	30012219
Muscle Hypotonia	Associate	22892528, 30012219
Neoplasms	Associate	22904677
Neurologic Manifestations	Associate	30012219
Optic Atrophy	Associate	30012219
Optic Nerve Hypoplasia	Associate	30012219
Pancreatic Neoplasms	Associate	28502252
Retinitis Pigmentosa	Associate	27764769
Seckel syndrome 1	Associate	31045292
Seckel syndrome 2	Associate	31045292
Short QT Syndrome 1	Associate	34281161
Thrombosis	Associate	12907444