Human Gene PIK3CD (ENST00000377346.9) from GENCODE V44
  Description: Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), transcript variant 1, mRNA. (from RefSeq NM_005026)
RefSeq Summary (NM_005026): Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010].
Gencode Transcript: ENST00000377346.9
Gencode Gene: ENSG00000171608.18
Transcript (Including UTRs)
   Position: hg38 chr1:9,651,731-9,729,114 Size: 77,384 Total Exon Count: 24 Strand: +
Coding Region
   Position: hg38 chr1:9,710,456-9,727,046 Size: 16,591 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 09:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:9,651,731-9,729,114)mRNA (may differ from genome)Protein (1044 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Short=PI3-kinase subunit delta; Short=PI3K-delta; Short=PI3Kdelta; Short=PtdIns-3-kinase subunit delta; EC=; AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta; Short=PtdIns-3-kinase subunit p110-delta; Short=p110delta;
FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.
CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
ENZYME REGULATION: Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells.
PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
SUBUNIT: Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS (By similarity). Interacts with HRAS.
TISSUE SPECIFICITY: Isoform 2 is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform 1 and isoform 2 are widely expressed. Isoform 1 is expressed predominantly in leukocytes.
PTM: Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity.
MISCELLANEOUS: IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response. Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy (PubMed:20940048; PubMed:17290298).
SIMILARITY: Belongs to the PI3/PI4-kinase family.
SIMILARITY: Contains 1 C2 PI3K-type domain.
SIMILARITY: Contains 1 PI3K-ABD domain.
SIMILARITY: Contains 1 PI3K-RBD domain.
SIMILARITY: Contains 1 PI3K/PI4K domain.
SIMILARITY: Contains 1 PIK helical domain.

-  Primer design for this transcript

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Click here to load the transcript sequence and exon structure into Primer3Plus

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-  MalaCards Disease Associations
  MalaCards Gene Search: PIK3CD
Diseases sorted by gene-association score: immunodeficiency 14* (1300), pasli disease* (750), epidermolysis bullosa simplex, dowling-meara type (7), lymphoproliferative syndrome 2 (7), lymphopenia (6), long qt syndrome 2 (5), long qt syndrome 5 (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • C569670 1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • C085911 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • C477872 IC 87114
  • C119129 18alpha-glycyrrhetinic acid
  • C009505 4,4'-diaminodiphenylmethane
  • C027576 4-hydroxy-2-nonenal
  • C547126 AZM551248
  • D001151 Arsenic
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 38.47 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 179.35 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -81.70209-0.391 Picture PostScript Text
3' UTR -742.702068-0.359 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016024 - ARM-type_fold
IPR008973 - C2_Ca/lipid-bd_dom_CaLB
IPR011009 - Kinase-like_dom
IPR000403 - PI3/4_kinase_cat_dom
IPR018936 - PI3/4_kinase_CS
IPR003113 - PI3K_adapt-bd_dom
IPR002420 - PI3K_C2_dom
IPR000341 - PI3K_Ras-bd_dom
IPR015433 - PI_Kinase
IPR001263 - PInositide-3_kin_accessory_dom

Pfam Domains:
PF00454 - Phosphatidylinositol 3- and 4-kinase
PF00792 - Phosphoinositide 3-kinase C2
PF02192 - PI3-kinase family, p85-binding domain
PF00794 - PI3-kinase family, ras-binding domain
PF00613 - Phosphoinositide 3-kinase family, accessory domain (PIK domain)

ModBase Predicted Comparative 3D Structure on O00329
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016303 1-phosphatidylinositol-3-kinase activity
GO:0016740 transferase activity
GO:0035004 phosphatidylinositol 3-kinase activity
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process:
GO:0001779 natural killer cell differentiation
GO:0001816 cytokine production
GO:0002250 adaptive immune response
GO:0002376 immune system process
GO:0002551 mast cell chemotaxis
GO:0002679 respiratory burst involved in defense response
GO:0006468 protein phosphorylation
GO:0006935 chemotaxis
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007411 axon guidance
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010818 T cell chemotaxis
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0016310 phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0030101 natural killer cell activation
GO:0030154 cell differentiation
GO:0030168 platelet activation
GO:0030217 T cell differentiation
GO:0030335 positive regulation of cell migration
GO:0030593 neutrophil chemotaxis
GO:0033031 positive regulation of neutrophil apoptotic process
GO:0035747 natural killer cell chemotaxis
GO:0035754 B cell chemotaxis
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0043303 mast cell degranulation
GO:0045087 innate immune response
GO:0046854 phosphatidylinositol phosphorylation
GO:0048015 phosphatidylinositol-mediated signaling
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0051897 positive regulation of protein kinase B signaling
GO:0060374 mast cell differentiation
GO:0072672 neutrophil extravasation

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005942 phosphatidylinositol 3-kinase complex
GO:0042629 mast cell granule

-  Descriptions from all associated GenBank mRNAs
  AK314191 - Homo sapiens cDNA, FLJ94916, highly similar to Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD), mRNA.
U86453 - Human phosphatidylinositol 3-kinase catalytic subunit p110delta mRNA, complete cds.
Y10055 - Homo sapiens mRNA for phosphoinositide 3-kinase.
BC030263 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide, mRNA (cDNA clone IMAGE:5215630), with apparent retained intron.
BC150297 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide, mRNA (cDNA clone MGC:167031 IMAGE:8860364), complete cds.
BC132919 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide, mRNA (cDNA clone MGC:164550 IMAGE:40146941), complete cds.
BC132921 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide, mRNA (cDNA clone MGC:164552 IMAGE:40146943), complete cds.
BC144264 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide, mRNA (cDNA clone MGC:177801 IMAGE:9052784), complete cds.
JN190435 - Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide variant p37delta (PIK3CD) mRNA, complete cds, alternatively spliced.
JD443472 - Sequence 424496 from Patent EP1572962.
JD139324 - Sequence 120348 from Patent EP1572962.
JD268316 - Sequence 249340 from Patent EP1572962.
JD473056 - Sequence 454080 from Patent EP1572962.
JD446015 - Sequence 427039 from Patent EP1572962.
U57843 - Human phosphatidylinositol 3-kinase delta catalytic subunit mRNA, complete cds.
KJ891810 - Synthetic construct Homo sapiens clone ccsbBroadEn_01204 PIK3CD gene, encodes complete protein.
KR712001 - Synthetic construct Homo sapiens clone CCSBHm_00034604 PIK3CD (PIK3CD) mRNA, encodes complete protein.
KU612116 - Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) mRNA, complete cds, alternatively spliced.
KU612117 - Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta short variant 20 (PIK3CD) mRNA, complete cds, alternatively spliced.
KU612118 - Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta short variant 8 (PIK3CD) mRNA, complete cds, alternatively spliced.
KU612119 - Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta short variant 8/20 (PIK3CD) mRNA, complete cds, alternatively spliced.
DQ263594 - Homo sapiens phosphoinositide-3-kinase B mRNA, complete cds.
DQ263595 - Homo sapiens phosphoinositide-3-kinase C mRNA, complete cds.
DQ263596 - Homo sapiens phosphoinositide-3-kinase D mRNA, complete cds.
AB208835 - Homo sapiens mRNA for phosphoinositide-3-kinase, catalytic, delta polypeptide variant protein.
AK303425 - Homo sapiens cDNA FLJ51430 complete cds, highly similar to Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform (EC
JD380563 - Sequence 361587 from Patent EP1572962.
JD076432 - Sequence 57456 from Patent EP1572962.
JD168131 - Sequence 149155 from Patent EP1572962.
JD452105 - Sequence 433129 from Patent EP1572962.
JD494415 - Sequence 475439 from Patent EP1572962.
JD163538 - Sequence 144562 from Patent EP1572962.
JD190045 - Sequence 171069 from Patent EP1572962.
JD187247 - Sequence 168271 from Patent EP1572962.
JD183500 - Sequence 164524 from Patent EP1572962.
JD482322 - Sequence 463346 from Patent EP1572962.
JD104475 - Sequence 85499 from Patent EP1572962.
JD373965 - Sequence 354989 from Patent EP1572962.
JD566884 - Sequence 547908 from Patent EP1572962.
JD531757 - Sequence 512781 from Patent EP1572962.
JD333234 - Sequence 314258 from Patent EP1572962.
JD089090 - Sequence 70114 from Patent EP1572962.
JD218794 - Sequence 199818 from Patent EP1572962.
JD099253 - Sequence 80277 from Patent EP1572962.
JD441719 - Sequence 422743 from Patent EP1572962.
JD448901 - Sequence 429925 from Patent EP1572962.
JD221815 - Sequence 202839 from Patent EP1572962.
JD201988 - Sequence 183012 from Patent EP1572962.
JD168319 - Sequence 149343 from Patent EP1572962.
JD410574 - Sequence 391598 from Patent EP1572962.
JD535223 - Sequence 516247 from Patent EP1572962.
JD241560 - Sequence 222584 from Patent EP1572962.
JD515126 - Sequence 496150 from Patent EP1572962.
JD163192 - Sequence 144216 from Patent EP1572962.
JD064970 - Sequence 45994 from Patent EP1572962.
JD269882 - Sequence 250906 from Patent EP1572962.
JD305185 - Sequence 286209 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00562 - Inositol phosphate metabolism
hsa04012 - ErbB signaling pathway
hsa04062 - Chemokine signaling pathway
hsa04070 - Phosphatidylinositol signaling system
hsa04150 - mTOR signaling pathway
hsa04210 - Apoptosis
hsa04370 - VEGF signaling pathway
hsa04510 - Focal adhesion
hsa04620 - Toll-like receptor signaling pathway
hsa04630 - Jak-STAT signaling pathway
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04662 - B cell receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway
hsa04666 - Fc gamma R-mediated phagocytosis
hsa04670 - Leukocyte transendothelial migration
hsa04722 - Neurotrophin signaling pathway
hsa04810 - Regulation of actin cytoskeleton
hsa04910 - Insulin signaling pathway
hsa04914 - Progesterone-mediated oocyte maturation
hsa04930 - Type II diabetes mellitus
hsa04960 - Aldosterone-regulated sodium reabsorption
hsa05100 - Bacterial invasion of epithelial cells
hsa05142 - Chagas disease
hsa05200 - Pathways in cancer
hsa05210 - Colorectal cancer
hsa05211 - Renal cell carcinoma
hsa05212 - Pancreatic cancer
hsa05213 - Endometrial cancer
hsa05214 - Glioma
hsa05215 - Prostate cancer
hsa05218 - Melanoma
hsa05220 - Chronic myeloid leukemia
hsa05221 - Acute myeloid leukemia
hsa05222 - Small cell lung cancer
hsa05223 - Non-small cell lung cancer

BioCyc Knowledge Library
PWY-6352 - 3-phosphoinositide biosynthesis
PWY-6371 - superpathway of inositol phosphate compounds

Reactome (by CSHL, EBI, and GO)

Protein O00329 (Reactome details) participates in the following event(s):

R-HSA-508247 Gab2 binds the p85 subunit of Class 1A PI3 kinases
R-HSA-879917 CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated
R-HSA-914182 14-3-3 zeta binding allows recruitment of PI3K
R-HSA-912629 CBL is tyrosine phosphorylated
R-HSA-2045911 BCAP Signalosome phosphorylates PI(4,5)P2 forming PI(3,4,5)P3
R-HSA-2076220 CD19 Signalosome phosphorylates PI(4,5)P2 forming PI(3,4,5)P3
R-HSA-1676109 PI4P is phosphorylated to PI(3,4)P2 by PI3K3C[2] at the plasma membrane
R-HSA-1676048 PI(4,5)P2 is phosphorylated to PI(3,4,5)P3 by PIK3C[1] at the plasma membrane
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-8853659 RET signaling
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-451927 Interleukin-2 family signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-422475 Axon guidance
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-1280218 Adaptive Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-1266738 Developmental Biology
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1483255 PI Metabolism
R-HSA-168256 Immune System
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-1483257 Phospholipid metabolism
R-HSA-5663202 Diseases of signal transduction
R-HSA-162582 Signal Transduction
R-HSA-556833 Metabolism of lipids
R-HSA-1643685 Disease
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A6NCG0, ENST00000377346.1, ENST00000377346.2, ENST00000377346.3, ENST00000377346.4, ENST00000377346.5, ENST00000377346.6, ENST00000377346.7, ENST00000377346.8, G1FFP1, NM_005026, O00329, O15445, PK3CD_HUMAN, Q5SR49, uc001aqb.1, uc001aqb.2, uc001aqb.3, uc001aqb.4, uc001aqb.5, uc001aqb.6
UCSC ID: ENST00000377346.9
RefSeq Accession: NM_005026
Protein: O00329 (aka PK3CD_HUMAN or P11D_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.