Table 3 Shared autoimmune disease loci and biologic pathways that are implicated according to the NCBI database (entrez Gene summary) or UniProtKB/Swiss-Prot
From: Emerging patterns of genetic overlap across autoimmune disorders
Shared loci | Biologic pathways |
|---|---|
ANGPT1 (Angiopoietin 1) | Roles in vascular development and angiogenesis |
BLK (B lymphoid tyrosine kinase) | B-cell receptor signaling and B-cell development |
CCNY (Cyclin Y) | Control of cell division cycles and regulation of cyclin-dependent kinases |
CCR3 (Chemokine receptor 3) | Binds to eotaxin, eotaxin-3, MCP-3, MCP-4, RANTES and MIP-1 |
CCR7 (Chemokine receptor 7) | Receptor for the MIP-3-beta chemokine |
CD40 | Member of the TNF-receptor superfamily; receptor for CD40L |
CD226 | Receptor involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cells |
COG6 (Component of oligomeric Golgi complex 6) | Required for normal Golgi function |
CTLA4 (Cytotoxic T-lymphocyte-associated protein 4) | Negative regulator of T-cell responses |
HERC2 (Hect domain and RLD 2) | E3 ubiquitin-protein ligase |
FCGR2A (Fc fragment of IgG) | Binds to the Fc region of immunoglobulins gamma |
ICOSLG (Inducible T-cell co-stimulator ligand) | Co-stimulatory signal for T-cell proliferation and cytokine secretion. Ligand for the T-cell-specific cell surface receptor ICOS |
IKZF1 (IKAROS family zinc finger 1) | Transcriptional regulator of hematopoietic cell differentiation |
IL10 | Inhibits the synthesis of a number of cytokines, including interferon-gamma, IL-2, IL-3, TNF and GM-CSF; produced by activated macrophages and by helper T-cells |
IL12A | Cytokine that can act as a growth factor for activated T and NK cells |
IL18RAP | NFkB and JNK activation (IL-18 dependent) |
IL2/IL21 | Cytokines required for T-cell or B-cell proliferation |
IL23R | Binds IL23 and mediates T-cell and NK cell stimulation |
IL26 | Activates STAT1 and STAT3, MAPK1/3 (ERK1/2), JUN and AKT |
IL27 | Broad functions in adaptive immunity |
IRF5 (Interferon regulatory factor 5) | Transcription factor involved in virus-mediated activation of interferon |
IRF8 (Interferon regulatory factor 8) | Plays a negative regulatory role in cells of the immune system |
IRGM (Immunity-related GTPase family, M) | Might play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens |
KIF5A (Kinesin family member 5A) | Microtubule-dependent motor required for intracellular protein transport |
LPP (LIM-domain-containing preferred translocation partner in lipoma) | Role in cell shape and motility |
MMEL1 (Membrane metallo-endopeptidase-like 1) | Metalloprotease involved in sperm function |
TNFSF14 | Activates NFkB and stimulates T-cell proliferation |
ORMDL3 (ORM1-like 3) | Might indirectly regulate endoplasmic reticulum-mediated Ca2+ signaling |
PLCL1 (Phospholipase C-like 1) | Involved in an inositol phospholipid-based intracellular signaling cascade |
PRKCQ (Protein kinase C theta) | TCR-mediated T-cell activation |
PTPN2 (Protein tyrosine phosphatase, non-receptor type 2) | Lymphocyte cell signaling |
PTPN22 | Involved in the TCR signaling pathway |
PUS10 (Pseudouridylate synthase 10) | Post-transcriptional nucleotide modification of RNAs |
RGS1 (Regulator of G-protein signaling 1) | Might be involved in the regulation of B cell activation and proliferation |
RPL19P8 (Ribosomal protein L19 pseudogene 8) | Pseudogene |
SH2B3 (SH2B adaptor protein 3) | T-cell receptor activation signaling |
STAT3 (Signal transducer and activator of transcription 3) | Th17 differentiation pathway |
STAT4 (Signal transducer and activator of transcription 4) | Th1 differentiation (interferon-gamma expression) |
TAGAP (T-cell activation RhoGTPase activating protein) | T-cell activation |
TNFAIP3 | Negative regulator of the TNF- or LPS-mediated activation of NF-kappa-B |
TNFSF15 | Mediates activation of NF-kappa-B |
TRAF1 (TNF receptor-associated factor 1) | Adapter molecule that regulates the activation of NF-kappa-B and JNK |
UBE2L3 (Ubiquitin-conjugating enzyme E2L 3) | Ubiquitination of intracellular component |
VEGFA (Vascular endothelial growth factor A) | Signaling protein involved in the regulation of angiogenesis and vasculogenesis |
VTCN1 (V-set domain containing T cell activation inhibitor 1) | Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity |
ZGPAT (Zinc finger, CCCH-type with G patch domain) | Negatively regulates expression of epidermal growth factor receptor (EGFR) |