Details for: ATP10A

Gene ID: 57194

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ATP10A

Ensembl ID: ENSG00000206190

Description: ATPase phospholipid transporting 10A (putative)

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • cerebral cortex endothelial cell CL1001602
    CSI 50.45
    rCSI 87.26%
    PRS 91.02
  • renal interstitial pericyte CL1001318
    CSI 15.43
    rCSI 42.52%
    PRS 93.07
  • ependymal cell CL0000065
    CSI 11.4
    rCSI 23.12%
    PRS 80.25
  • podocyte CL0000653
    CSI 8.98
    rCSI 39.89%
    PRS 94.33
  • alveolar macrophage CL0000583
    CSI 6.94
    rCSI 11.44%
    PRS 95.52
  • vascular leptomeningeal cell CL4023051
    CSI 6.3
    rCSI 11.05%
    PRS 92.35
  • hepatic stellate cell CL0000632
    CSI 6.22
    rCSI 23.32%
    PRS 91.83
  • sncg GABAergic cortical interneuron CL4023015
    CSI 5.48
    rCSI 8.81%
    PRS 86.37
  • lung ciliated cell CL1000271
    CSI 5.18
    rCSI 6%
    PRS 90.29
  • adipocyte CL0000136
    CSI 5.07
    rCSI 6.51%
    PRS 88.14
  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 4.61
    rCSI 3.24%
    PRS 97.82
  • endothelial cell of vascular tree CL0002139
    CSI 4.4
    rCSI 24.07%
    PRS 91.05
  • contractile cell CL0000183
    CSI 4.22
    rCSI 12.46%
    PRS 94.53
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 4.14
    rCSI 5.86%
    PRS 93.08
  • early lymphoid progenitor CL0000936
    CSI 3.86
    rCSI 3.39%
    PRS 96.47
  • subcutaneous adipocyte CL0002521
    CSI 3.78
    rCSI 19.38%
    PRS 95.55
  • fibroblast of cardiac tissue CL0002548
    CSI 3.73
    rCSI 17.89%
    PRS 95.25
  • group 3 innate lymphoid cell CL0001071
    CSI 3.53
    rCSI 2.65%
    PRS 96.15
  • smooth muscle cell CL0000192
    CSI 3.46
    rCSI 8.25%
    PRS 90.23
  • mature T cell CL0002419
    CSI 3.42
    rCSI 2.66%
    PRS 98.42
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.15
    rCSI 8.21%
    PRS 95.68
  • pulmonary alveolar type 1 cell CL0002062
    CSI 3.11
    rCSI 17.95%
    PRS 92.32
  • melanocyte CL0000148
    CSI 3.08
    rCSI 2.28%
    PRS 92.19
  • lung pericyte CL0009089
    CSI 3.03
    rCSI 8%
    PRS 96.86
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.02
    rCSI 2.34%
    PRS 96.05
  • innate lymphoid cell CL0001065
    CSI 2.9
    rCSI 5.98%
    PRS 88.62
  • endocardial cell CL0002350
    CSI 2.82
    rCSI 13.5%
    PRS 91.92
  • pulmonary alveolar type 2 cell CL0002063
    CSI 2.81
    rCSI 4.35%
    PRS 94.71
  • bronchus fibroblast of lung CL2000093
    CSI 2.79
    rCSI 2.27%
    PRS 94.19
  • brain vascular cell CL4023072
    CSI 2.76
    rCSI 28.58%
    PRS 89.97
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.7
    rCSI 4.31%
    PRS 95.78
  • epicardial adipocyte CL1000309
    CSI 2.66
    rCSI 8.65%
    PRS 92.39
  • parietal epithelial cell CL1000452
    CSI 2.6
    rCSI 6.94%
    PRS 90.97
  • chondrocyte CL0000138
    CSI 2.53
    rCSI 4.02%
    PRS 91.22
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.51
    rCSI 7.26%
    PRS 93.89
  • lung secretory cell CL1000272
    CSI 2.43
    rCSI 6.01%
    PRS 95.63
  • myoepithelial cell CL0000185
    CSI 2.41
    rCSI 6.1%
    PRS 95.81
  • blood vessel smooth muscle cell CL0019018
    CSI 2.38
    rCSI 19.35%
    PRS 93.38
  • tracheobronchial smooth muscle cell CL0019019
    CSI 2.36
    rCSI 4.16%
    PRS 96.22
  • alveolar adventitial fibroblast CL4028006
    CSI 2.28
    rCSI 3.6%
    PRS 95.26
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.2
    rCSI 1.69%
    PRS 96.58
  • common lymphoid progenitor CL0000051
    CSI 2.18
    rCSI 2.92%
    PRS 98.54
  • basal cell of epidermis CL0002187
    CSI 2.06
    rCSI 3.65%
    PRS 69.79
  • CD14-positive monocyte CL0001054
    CSI 1.89
    rCSI 2.35%
    PRS 97.89
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.88
    rCSI 6.78%
    PRS 83.78
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.47
    rCSI 3.56%
    PRS 83.53
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.33
    rCSI 2.23%
    PRS 85.63
  • smooth muscle cell of the pulmonary artery CL0002591
    CSI 0.94
    rCSI 7.19%
    PRS 95.04
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.82
    rCSI 2.55%
    PRS 86.44
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.61
    rCSI 6.44%
    PRS 91.37

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ATP10A](/details-gene/57194) is a protein-coding gene located on human chromosome 15q12 that encodes a putative P4-type ATPase. This protein functions as a phospholipid-transporting enzyme, or "flippase," which actively translocates specific lipids, such as phosphatidylcholine and glycosylceramides, across cell membranes in an ATP-dependent manner ([Link](https://doi.org/10.1074/jbc.m115.655191), [Link](https://doi.org/10.1074/jbc.ra118.005876)). Its activity is integral to maintaining membrane asymmetry, regulating cell shape ([GO:0008360](https://www.ebi.ac.uk/QuickGO/term/GO:0008360)), and contributing to membrane dynamics like tubulation ([GO:1903527](https://www.ebi.ac.uk/QuickGO/term/GO:1903527)). Expression data highlights its exceptional significance in [cerebral cortex endothelial cell](/details-cell/CL1001602), suggesting a primary role in specialized barrier tissues, particularly the neurovascular unit. Its chromosomal location and expression pattern have also associated it with imprinted neurodevelopmental disorders like Angelman syndrome ([Link](https://doi.org/10.1086/320616)). ## Cellular Roles and Expression Landscape The expression profile of [ATP10A](/details-gene/57194) indicates highly specialized functions in distinct cell populations. **Overall**, the gene exhibits its most profound significance in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 50.45), identifying it as a key molecular player in the blood-brain barrier. Beyond this primary site, [ATP10A](/details-gene/57194) shows notable significance in other specialized cell types, suggesting diverse roles in tissue homeostasis and barrier function: * **Renal System:** High significance in [renal interstitial pericyte](/details-cell/CL1001318) and [podocyte](/details-cell/CL0000653) points towards a potential role in maintaining the structure and function of the kidney's glomerular filtration barrier. * **Central Nervous System:** Significant expression in [ependymal cell](/details-cell/CL0000065), [vascular leptomeningeal cell](/details-cell/CL4023051), and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) suggests its involvement in both cerebrospinal fluid homeostasis and neuronal membrane function. * **Other Barrier and Specialized Cells:** Its activity is also highlighted in [alveolar macrophage](/details-cell/CL0000583) and [lung ciliated cell](/details-cell/CL1000271), implying a role in pulmonary immune surveillance and mucociliary clearance. Modest significance is also observed in immune progenitors like the [early lymphoid progenitor](/details-cell/CL0000936) and mature T cells like the [naive thymus-derived CD8-positive, alpha-beta T cell](/details-cell/CL0000900), indicating a potential contribution to immune cell membrane dynamics. ## Pathways and Molecular Function The molecular functions of [ATP10A](/details-gene/57194) are centered on its role as an ATPase-coupled intramembrane lipid transporter ([GO:0140326](https://www.ebi.ac.uk/QuickGO/term/GO:0140326)). It belongs to the P4-ATPase family, which establishes and maintains the asymmetric distribution of phospholipids in cellular membranes. Key annotated functions include: * **Lipid Translocation:** It specifically demonstrates phosphatidylcholine flippase activity ([GO:0140345](https://www.ebi.ac.uk/QuickGO/term/GO:0140345)) and glycosylceramide flippase activity ([GO:0140351](https://www.ebi.ac.uk/QuickGO/term/GO:0140351)), contributing directly to phospholipid translocation ([GO:0045332](https://www.ebi.ac.uk/QuickGO/term/GO:0045332)) ([Link](https://doi.org/10.1074/jbc.ra118.005876)). * **Membrane Dynamics:** This flippase activity is crucial for regulating biophysical properties of the membrane, driving processes such as membrane tubulation and vesicle formation ([Link](https://doi.org/10.15252/embj.201797705)). This is reflected in its association with the positive regulation of membrane tubulation ([GO:1903527](https://www.ebi.ac.uk/QuickGO/term/GO:1903527)). * **Cellular Localization:** Its functions are carried out primarily at the [plasma membrane](/details-cell/GO0005886) and within the [endoplasmic reticulum](/details-cell/GO0005783), consistent with its role in lipid trafficking and membrane biogenesis. * **Broader Transport Pathways:** Functionally, it is part of the larger network of [ion transport by P-type ATPases](/details-pathway/R-HSA-936837) and the overall [transport of small molecules](/details-pathway/R-HSA-382551), highlighting its fundamental role in cellular transport machinery. ## Research Directions The unique expression pattern and molecular function of [ATP10A](/details-gene/57194) suggest several avenues for future research, particularly regarding its role in tissue barriers and neurological health. ### Proposed Hypotheses: 1. **Blood-Brain Barrier Integrity:** Given its exceptionally high significance in [cerebral cortex endothelial cell](/details-cell/CL1001602), [ATP10A](/details-gene/57194) is hypothesized to be a critical regulator of blood-brain barrier (BBB) integrity by maintaining the specific lipid composition and low transcytotic activity characteristic of these cells. Its dysregulation could lead to increased BBB permeability, a hallmark of many neurological diseases. 2. **Podocyte Structural Maintenance:** The high significance of [ATP10A](/details-gene/57194) in [podocyte](/details-cell/CL0000653)s, combined with its established role in regulating cell shape ([GO:0008360](https://www.ebi.ac.uk/QuickGO/term/GO:0008360)), suggests that it is essential for maintaining the complex architecture of podocyte foot processes. Loss of [ATP10A](/details-gene/57194) function may contribute to podocyte effacement and the development of proteinuric kidney diseases. 3. **Neuronal Membrane Homeostasis and Neurodevelopment:** Based on its link to the Angelman syndrome locus ([Link](https://doi.org/10.1038/ng0501-19)) and expression in neurons like the [sncg GABAergic cortical interneuron](/details-cell/CL4023015), altered [ATP10A](/details-gene/57194) activity may disrupt neuronal membrane asymmetry and lipid signaling, contributing to synaptic dysfunction and the pathophysiology of certain neurodevelopmental disorders ([Link](https://doi.org/10.1016/j.neuron.2015.11.009)). ### Key Experimental Approach: To test the hypothesis regarding the role of **[ATP10A](/details-gene/57194)** in blood-brain barrier integrity (Hypothesis 1), an *in vivo* study using a conditional knockout mouse model would be highly informative. An *Atp10a* floxed mouse could be crossed with a mouse line expressing Cre recombinase under an endothelial-specific promoter (e.g., Cdh5-Cre). The resulting offspring would lack [ATP10A](/details-gene/57194) specifically in endothelial cells. BBB permeability could then be quantitatively assessed by intravenous injection of fluorescent tracers of different molecular weights (e.g., sodium fluorescein, dextrans) and measuring their extravasation into the brain parenchyma. Furthermore, primary brain microvascular endothelial cells could be isolated from these mice for lipidomic analysis to determine specific changes in the plasma membrane lipid profile. ### Therapeutic Potential: As a membrane-bound enzyme, [ATP10A](/details-gene/57194) presents a druggable target. Its high specificity for cerebral endothelial cells suggests it could be a target for modulating BBB permeability. For instance, a small molecule inhibitor of [ATP10A](/details-gene/57194) could be developed to transiently open the BBB, enhancing the delivery of therapeutics to the central nervous system. Conversely, in conditions where its function is compromised (e.g., certain neurodevelopmental or neurodegenerative disorders), developing a small molecule activator could represent a novel strategy to restore membrane homeostasis and barrier function. Given its potential link to loss-of-function pathologies, activation would likely be the primary therapeutic goal in those specific disease contexts.

Genular Protein ID: 2528698443

Symbol: AT10A_HUMAN

Name: Phospholipid-transporting ATPase VA

UniProtKB Accession Codes:

O60312 Q4G0S9 Q969I4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 31 ChiTaRS 1 ComplexPortal 1 DNASU 1 DisGeNET 1 EC 1 EMBL 25 Ensembl 4 ExpressionAtlas 1 GO 16 Gene3D 4 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 2 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 3 Rhea 4 SFLD 2 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11326269

Title: A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome.

PubMed ID: 11326269

DOI: 10.1038/ng0501-19

PubMed ID: 11353404

Title: The human aminophospholipid-transporting ATPase gene ATP10C maps adjacent to UBE3A and exhibits similar imprinted expression.

PubMed ID: 11353404

DOI: 10.1086/320616

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9628581

Title: Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9628581

DOI: 10.1093/dnares/5.1.31

PubMed ID: 21914794

Title: ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner.

PubMed ID: 21914794

DOI: 10.1074/jbc.m111.281006

PubMed ID: 25947375

Title: Phospholipid Flippase ATP10A Translocates Phosphatidylcholine and Is Involved in Plasma Membrane Dynamics.

PubMed ID: 25947375

DOI: 10.1074/jbc.m115.655191

PubMed ID: 26637798

Title: Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.

PubMed ID: 26637798

DOI: 10.1016/j.neuron.2015.11.009

PubMed ID: 29599178

Title: Phospholipid-flipping activity of P4-ATPase drives membrane curvature.

PubMed ID: 29599178

DOI: 10.15252/embj.201797705

PubMed ID: 30530492

Title: Yeast and human P4-ATPases transport glycosphingolipids using conserved structural motifs.

PubMed ID: 30530492

DOI: 10.1074/jbc.ra118.005876

Sequence Information:

  • Length: 1499
  • Mass: 167688
  • Checksum: D4996A4D0635A68D
  • Sequence:
    • MEREPAGTEE PGPPGRRRRR EGRTRTVRSN LLPPPGAEDP AAGAAKGERR RRRGCAQHLA 
DNRLKTTKYT LLSFLPKNLF EQFHRPANVY FVFIALLNFV PAVNAFQPGL ALAPVLFILA 
ITAFRDLWED YSRHRSDHKI NHLGCLVFSR EEKKYVNRFW KEIHVGDFVR LRCNEIFPAD 
ILLLSSSDPD GLCHIETANL DGETNLKRRQ VVRGFSELVS EFNPLTFTSV IECEKPNNDL 
SRFRGCIIHD NGKKAGLYKE NLLLRGCTLR NTDAVVGIVI YAGHETKALL NNSGPRYKRS 
KLERQMNCDV LWCVLLLVCM SLFSAVGHGL WIWRYQEKKS LFYVPKSDGS SLSPVTAAVY 
SFLTMIIVLQ VLIPISLYVS IEIVKACQVY FINQDMQLYD EETDSQLQCR ALNITEDLGQ 
IQYIFSDKTG TLTENKMVFR RCTVSGVEYS HDANAQRLAR YQEADSEEEE VVPRGGSVSQ 
RGSIGSHQSV RVVHRTQSTK SHRRTGSRAE AKRASMLSKH TAFSSPMEKD ITPDPKLLEK 
VSECDKSLAV ARHQEHLLAH LSPELSDVFD FFIALTICNT VVVTSPDQPR TKVRVRFELK 
SPVKTIEDFL RRFTPSCLTS GCSSIGSLAA NKSSHKLGSS FPSTPSSDGM LLRLEERLGQ 
PTSAIASNGY SSQADNWASE LAQEQESERE LRYEAESPDE AALVYAARAY NCVLVERLHD 
QVSVELPHLG RLTFELLHTL GFDSVRKRMS VVIRHPLTDE INVYTKGADS VVMDLLQPCS 
SVDARGRHQK KIRSKTQNYL NVYAAEGLRT LCIAKRVLSK EEYACWLQSH LEAESSLENS 
EELLFQSAIR LETNLHLLGA TGIEDRLQDG VPETISKLRQ AGLQIWVLTG DKQETAVNIA 
YACKLLDHDE EVITLNATSQ EACAALLDQC LCYVQSRGLQ RAPEKTKGKV SMRFSSLCPP 
STSTASGRRP SLVIDGRSLA YALEKNLEDK FLFLAKQCRS VLCCRSTPLQ KSMVVKLVRS 
KLKAMTLAIG DGANDVSMIQ VADVGVGISG QEGMQAVMAS DFAVPKFRYL ERLLILHGHW 
CYSRLANMVL YFFYKNTMFV GLLFWFQFFC GFSASTMIDQ WYLIFFNLLF SSLPPLVTGV 
LDRDVPANVL LTNPQLYKSG QNMEEYRPRT FWFNMADAAF QSLVCFSIPY LAYYDSNVDL 
FTWGTPIVTI ALLTFLLHLG IETKTWTWLN WITCGFSVLL FFTVALIYNA SCATCYPPSN 
PYWTMQALLG DPVFYLTCLM TPVAALLPRL FFRSLQGRVF PTQLQLARQL TRKSPRRCSA 
PKETFAQGRL PKDSGTEHSS GRTVKTSVPL SQPSWHTQQP VCSLEASGEP STVDMSMPVR 
EHTLLEGLSA PAPMSSAPGE AVLRSPGGCP EESKVRAAST GRVTPLSSLF SLPTFSLLNW 
ISSWSLVSRL GSVLQFSRTE QLADGQAGRG LPVQPHSGRS GLQGPDHRLL IGASSRRSQ