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ATP8A2 ATPase phospholipid transporting 8A2 [ Homo sapiens (human) ]

Gene ID: 51761, updated on 27-Nov-2024

Summary

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Official Symbol
ATP8A2provided by HGNC
Official Full Name
ATPase phospholipid transporting 8A2provided by HGNC
Primary source
HGNC:HGNC:13533
See related
Ensembl:ENSG00000132932 MIM:605870; AllianceGenome:HGNC:13533
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IB; ATP; ML-1; ATPIB; CAMRQ4
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 the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]
Expression
Biased expression in brain (RPKM 6.4), testis (RPKM 2.7) and 2 other tissues See more
Orthologs
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Genomic context

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See ATP8A2 in Genome Data Viewer
Location:
13q12.13
Exon count:
47
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (25371974..26025851)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (24581610..25239722)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (25946112..26599989)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7487 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_32788 Neighboring gene CRISPRi-validated cis-regulatory element chr13.188 Neighboring gene nucleoporin 58 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr13:25971441-25972042 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr13:25972043-25972644 Neighboring gene elongin B pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:26028835-26029335 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr13:26052317-26053192 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:26086829-26087701 Neighboring gene NANOG hESC enhancer GRCh37_chr13:26118592-26119123 Neighboring gene RNA, U6 small nuclear 78, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7488 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7489 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr13:26484777-26485332 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr13:26485333-26485887 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:26548551-26549090 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:26549091-26549629 Neighboring gene uncharacterized LOC105370122 Neighboring gene RNA, 7SL, cytoplasmic 741, pseudogene Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:26550993-26551936 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:26552889-26553440 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:26585998-26586498 Neighboring gene RNY1 pseudogene 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:26586499-26586999 Neighboring gene long intergenic non-protein coding RNA 415 Neighboring gene shisa family member 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. P4 ATPases: flippases in health and disease. van der Mark VA, et al. Int J Mol Sci, 2013 Apr 11. PMID 23579954, Free PMC Article
  2. Changes in levels of normal ML-1 gene transcripts associated with the conversion of human nontumorigenic to tumorigenic phenotypes. Sun XL, et al. Gene Expr, 1999. PMID 10551800, Free PMC Article
  3. Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. Onat OE, et al. Eur J Hum Genet, 2013 Mar. PMID 22892528, Free PMC Article
  4. Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases. Matsell E, et al. Dis Model Mech, 2024 Jun 1. PMID 38436085, Free PMC Article
  5. P4-ATPases: lipid flippases in cell membranes. Lopez-Marques RL, et al. Pflugers Arch, 2014 Jul. PMID 24077738, Free PMC Article

See all (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.
    Title: Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.
  2. On the track of the lipid transport pathway of the phospholipid flippase ATP8A2 - Mutation analysis of residues of the transmembrane segments M1, M2, M3 and M4.
    Title: On the track of the lipid transport pathway of the phospholipid flippase ATP8A2 - Mutation analysis of residues of the transmembrane segments M1, M2, M3 and M4.
  3. Two Siblings with Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome 4 and a Novel Variant of ATP8A2.
    Title: Two Siblings with Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome 4 and a Novel Variant of ATP8A2.
  4. Novel variants in critical domains of ATP8A2 and expansion of clinical spectrum.
    Title: Novel variants in critical domains of ATP8A2 and expansion of clinical spectrum.
  5. Congenital ataxia due to novel variant in ATP8A2.
    Title: Congenital ataxia due to novel variant in ATP8A2.
  6. ATP8A2-related disorders as recessive cerebellar ataxia.
    Title: ATP8A2-related disorders as recessive cerebellar ataxia.
  7. Functional analysis of the effect of disease-associated missense mutations on ATP8A2 show that the p.Ile376Met and p.Lys429Met variants fold in a native-like conformation, but lack key amino acid residues required for ATP-dependent lipid transport. In contrast, the p.Lys429Asn, pAla544Pro, p.Arg625Trp, and p.Trp702Arg variants are highly misfolded and undergo rapid proteosomal degradation.
    Title: Expression and functional characterization of missense mutations in ATP8A2 linked to severe neurological disorders.
  8. Using an electrophysiological method based on solid supported membranes, we observed the generation of a transient electrical current by the mammalian P4-ATPase ATP8A2 in the presence of ATP and the negatively charged lipid substrate phosphatidylserine, whereas only a diminutive current was generated with the lipid substrate phosphatidylethanolamine, which carries no or little charge under the conditions of the measuremen
    Title: Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic.
  9. Study describes a new ATP8A2 gene mutations associated with a novel syndrome that includes encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. The data expand both the genetic and phenotypic spectrum associated with ATP8A2 gene mutations.
    Title: New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy.
  10. ATP8A2 is involved in the development of the cerebro-cerebellar structures required for posture and gait.
    Title: Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4
MedGen: C3808977 OMIM: 615268 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
EBI GWAS Catalog
Genetic variants associated with disordered eating.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp434B1913

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables ATPase-coupled intramembrane lipid transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables magnesium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables phosphatidylethanolamine flippase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables phosphatidylserine flippase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables phosphatidylserine floppase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in aminophospholipid translocation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in detection of light stimulus involved in visual perception IEA
Inferred from Electronic Annotation
more info
  
involved_in determination of adult lifespan IEA
Inferred from Electronic Annotation
more info
  
involved_in eating behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in inner ear morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in involuntary skeletal muscle contraction IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in neurofilament cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
involved_in neuromuscular process controlling posture IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in phospholipid translocation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of multicellular organism growth IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of neuron projection development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of phospholipid translocation IEA
Inferred from Electronic Annotation
more info
  
involved_in response to auditory stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in retina layer formation IEA
Inferred from Electronic Annotation
more info
  
involved_in skin development IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Golgi membrane IEA
Inferred from Electronic Annotation
more info
  
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
located_in endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
part_of phospholipid-translocating ATPase complex IPI
Inferred from Physical Interaction
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in trans-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
phospholipid-transporting ATPase IB
Names
ATPase, aminophospholipid transporter, class I, type 8A, member 2
ATPase, aminophospholipid transporter-like, class I, type 8A, member 2
P4-ATPase flippase complex alpha subunit ATP8A2
probable phospholipid-transporting ATPase IB
NP_001300670.1
NP_001397934.1
NP_001397935.1
NP_057613.4
XP_005266476.1
XP_011533406.1
XP_011533409.1
XP_011533411.1
XP_011533415.1
XP_016876114.1
XP_016876115.1
XP_024305137.1
XP_047286339.1
XP_054230574.1
XP_054230575.1
XP_054230576.1
XP_054230577.1
XP_054230578.1
XP_054230579.1
XP_054230580.1
XP_054230581.1
XP_054230582.1
XP_054230583.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_042855.1 RefSeqGene

    Range
    4964..658841
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001313741.1 → NP_001300670.1  phospholipid-transporting ATPase IB isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and lacks an alternate in-frame exon in the central coding region. These differences cause translation initiation at a downstream start codon and result in an isoform (2) with a shorter N-terminus, and lacking an internal segment, compared to isoform 1.
    Source sequence(s)
    AK094653, AK126031, AK127263, AK302980, AL136438, AL138815, AL139004, AL390129, AL669971, BP396213, HY026915
    UniProtKB/TrEMBL
    B7Z880, Q6ZU25
    Conserved Domains (6) summary
    TIGR01652
    Location:28 → 1041
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase
    pfam00122
    Location:85 → 304
    E1-E2_ATPase; E1-E2 ATPase
    pfam13246
    Location:466 → 564
    Cation_ATPase; Cation transport ATPase (P-type)
    pfam16209
    Location:17 → 79
    PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal
    pfam16212
    Location:808 → 1034
    PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal
    cl21460
    Location:776 → 805
    HAD_like; Haloacid Dehalogenase-like Hydrolases

  2. NM_001411005.1 → NP_001397934.1  phospholipid-transporting ATPase IB isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL136438, AL138815, AL138958, AL139004, AL157366, AL356316, AL669971
    Consensus CDS
    CCDS91793.1
    UniProtKB/TrEMBL
    A0A804HKW9
    Related
    ENSP00000508103.1, ENST00000682472.1

  3. NM_001411006.1 → NP_001397935.1  phospholipid-transporting ATPase IB isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL136438, AL138815, AL138958, AL157366, AL356316, AL669971
    Consensus CDS
    CCDS91792.1
    UniProtKB/TrEMBL
    A0A804HI09
    Related
    ENSP00000506846.1, ENST00000683960.1

  4. NM_016529.6 → NP_057613.4  phospholipid-transporting ATPase IB isoform 1

    See identical proteins and their annotated locations for NP_057613.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AF236871, AK094653, AK126031, AK127263, AL136438, AL138815, AL138958, AL139004, AL390129, AL669971, BP396213, DA326706
    Consensus CDS
    CCDS41873.1
    UniProtKB/Swiss-Prot
    Q6ZSP3, Q9H527, Q9NPU6, Q9NTI2, Q9NTL2, Q9NYM3
    UniProtKB/TrEMBL
    A0A804HLG3
    Related
    ENSP00000371070.2, ENST00000381655.7
    Conserved Domains (1) summary
    TIGR01652
    Location:68 → 1106
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    25371974..26025851
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011535107.4 → XP_011533409.1  phospholipid-transporting ATPase IB isoform X8

    UniProtKB/TrEMBL
    A0A804HLG3
    Related
    ENSP00000508339.1, ENST00000683303.1
    Conserved Domains (6) summary
    TIGR01652
    Location:68 → 1051
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase
    pfam00122
    Location:125 → 344
    E1-E2_ATPase; E1-E2 ATPase
    pfam13246
    Location:506 → 604
    Cation_ATPase; Cation transport ATPase (P-type)
    pfam16209
    Location:57 → 119
    PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal
    pfam16212
    Location:848 → 1054
    PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal
    cl21460
    Location:816 → 845
    HAD_like; Haloacid Dehalogenase-like Hydrolases

  2. XM_011535113.3 → XP_011533415.1  phospholipid-transporting ATPase IB isoform X5

    UniProtKB/TrEMBL
    A0A804HKN1
    Conserved Domains (3) summary
    pfam00122
    Location:125 → 344
    E1-E2_ATPase; E1-E2 ATPase
    pfam13246
    Location:506 → 604
    Cation_ATPase; Cation transport ATPase (P-type)
    pfam16209
    Location:57 → 119
    PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal

  3. XM_017020626.2 → XP_016876115.1  phospholipid-transporting ATPase IB isoform X7

    UniProtKB/TrEMBL
    A0A804HKN1

  4. XM_017020625.3 → XP_016876114.1  phospholipid-transporting ATPase IB isoform X6

    UniProtKB/TrEMBL
    A0A804HKN1

  5. XM_047430383.1 → XP_047286339.1  phospholipid-transporting ATPase IB isoform X1

  6. XM_005266419.2 → XP_005266476.1  phospholipid-transporting ATPase IB isoform X1

    See identical proteins and their annotated locations for XP_005266476.1

    UniProtKB/TrEMBL
    Q6ZU25
    Related
    ENSP00000507489.1, ENST00000684424.1
    Conserved Domains (1) summary
    TIGR01652
    Location:28 → 1066
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

  7. XM_011535104.3 → XP_011533406.1  phospholipid-transporting ATPase IB isoform X2

    UniProtKB/TrEMBL
    Q6ZU25
    Related
    ENST00000683945.1
    Conserved Domains (6) summary
    TIGR01652
    Location:34 → 1066
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase
    pfam00122
    Location:85 → 304
    E1-E2_ATPase; E1-E2 ATPase
    pfam13246
    Location:466 → 564
    Cation_ATPase; Cation transport ATPase (P-type)
    pfam16209
    Location:34 → 79
    PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal
    pfam16212
    Location:808 → 1059
    PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal
    cl21460
    Location:776 → 805
    HAD_like; Haloacid Dehalogenase-like Hydrolases

  8. XM_011535109.4 → XP_011533411.1  phospholipid-transporting ATPase IB isoform X3

    See identical proteins and their annotated locations for XP_011533411.1

    UniProtKB/TrEMBL
    Q6ZU25
    Conserved Domains (5) summary
    TIGR01652
    Location:1 → 946
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase
    pfam00122
    Location:2 → 184
    E1-E2_ATPase; E1-E2 ATPase
    pfam13246
    Location:346 → 444
    Cation_ATPase; Cation transport ATPase (P-type)
    pfam16212
    Location:688 → 939
    PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal
    cl21460
    Location:656 → 685
    HAD_like; Haloacid Dehalogenase-like Hydrolases

  9. XM_024449369.1 → XP_024305137.1  phospholipid-transporting ATPase IB isoform X4

    UniProtKB/TrEMBL
    Q6ZU25
    Conserved Domains (1) summary
    TIGR01652
    Location:1 → 908
    ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_187593.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    489..133501 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    24581610..25239722
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054374602.1 → XP_054230577.1  phospholipid-transporting ATPase IB isoform X9

  2. XM_054374605.1 → XP_054230580.1  phospholipid-transporting ATPase IB isoform X10

  3. XM_054374606.1 → XP_054230581.1  phospholipid-transporting ATPase IB isoform X5

  4. XM_054374608.1 → XP_054230583.1  phospholipid-transporting ATPase IB isoform X7

  5. XM_054374607.1 → XP_054230582.1  phospholipid-transporting ATPase IB isoform X6

  6. XM_054374601.1 → XP_054230576.1  phospholipid-transporting ATPase IB isoform X1

  7. XM_054374599.1 → XP_054230574.1  phospholipid-transporting ATPase IB isoform X1

  8. XM_054374600.1 → XP_054230575.1  phospholipid-transporting ATPase IB isoform X2

  9. XM_054374603.1 → XP_054230578.1  phospholipid-transporting ATPase IB isoform X3

  10. XM_054374604.1 → XP_054230579.1  phospholipid-transporting ATPase IB isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NTI2.3 GenPept UniProtKB/Swiss-Prot:Q9NTI2

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