Property Summary

NCBI Gene PubMed Count 67
PubMed Score 203.53
PubTator Score 114.74

Knowledge Summary


No data available


  Disease (4)

Disease Target Count Z-score Confidence
Dementia 129 4.808 2.4
Osteopetrosis 40 3.942 2.0
Alzheimer's disease 644 3.211 1.6


 OMIM Phenotype (1)

Gene RIF (40)

26642091 the microglial membrane adaptor protein DAP12 was required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and the ensuing pain, but not for microglial proliferation
26337043 Impaired signaling by the TREM2-DAP12 pathway leads to altered immune responses in phagocytosis, cytokine production, and microglial proliferation and survival, thus contributing to disease pathogenesis. Review.
26001891 The different expression of DAP12 compared to TREM2 represents the first description of such variable expressivity in Nasu-Hakola disease (NHD) microglia.
25957402 results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.
25941351 T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor activity compared with standard first- and second-generation CD3zeta-based CARs in a xenograft model of mesothelioma highly resistant to immunotherapy.
25642940 isolated PMNs have an increased proportion of both TREM1 and DAP12 compared to normal healthy control
25487697 This study reveled that TYROBP having a central role in the bipolar disease and schizophrenia manifestation.
24935923 Data indicate that NKG2 receptor NKG2E was capable of associating with CD94 and DAP12 but that the complex was retained intracellularly at the endoplasmic reticulum.
24612676 Its mutation is a known genetic cause of Nasu-Hakola disease.
23810293 Macrophage traits in BRC cells facilitate the metastatic process and DAP12 expression might promote metastatic homing to bone and liver tissues.
23715743 DAP12 has a role in trafficking newly synthesized KIR to the cell surface. It interacts with an immature KIR2DS isoform likely initiating in the ER. DAP12also impacts KIR2DS surface stability.
23561520 dynamics and dimerization of the TM helix of DAP12 in the membrane bilayer
22080356 A molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in Nasu-Hakola disease.
21967868 the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells.
21841309 Data suggest that OSCAR is a collagen receptor that binds to specific collagen motifs and costimulates osteoclastogenesis in DAP12-deficient humans and mice.
21421043 DAP12 gene levels were not increased in the monocytes of schizophrenic, bioplar or major depressive disorder patients.
21263069 A transgenic mouse model demonstrates that induction of tolerance in Ly49H-positive natural killer (NK) cells by chronic exposure to virus-encoded ligand m157 requires signaling through the Ly49H adaptor protein DAP12, not the DAP10 adaptor protein.
20628624 Meta-analysis of gene-disease association. (HuGE Navigator)
20421649 These findings indicate that DAP12, possibly through association with TREM2, contributes to alveolar macrophage chemotaxis and recruitment to the lung and may mediate macrophage accumulation in lung diseases such as emphysema.
20212065 DAP12-associating lectin (MDL)-1 receptor is a key regulator of synovial injury and bone erosion in autoimmune joint inflammation.
19606219 describe the generation and the characterization of an anti-DAP12 monoclonal antibody. Using this novel reagent, we show that DAP12 expression is restricted to innate immune cells in basal condition
19120482 loss of function mutation results in recessive genetic disorder, Nasu-Hakola disease (bone development abnormalities and dementia at adolescence)
19075187 Downstream targets of DAP10 and DAP12 are constitutively activated in large granular lymphocyte leukemia cells, and expression of dominant-negative DAP10 and DAP12 dramatically reduces their lytic capacity.
19019460 the DAP12-TREM2 complex unlikely has a role in genetic susceptibility of multiple sclerosis
19019460 Observational study of gene-disease association. (HuGE Navigator)
17530208 Transcript analysis of DCs of PLOSL patients show that DAP12 deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences due to defects in the actin filaments.
17277102 activation signals delivered via DAP12 can be counterbalanced by the adaptor NTAL
17202323 KIR3DS1 associates with the ITAM-bearing adaptor, DAP12
17125796 This is the first case of Nasu-Hakola disease caused by compound heterozygosity for loss-of-function mutations in DAP12.
17100880 This review discusses the dual functionality of DAP12 and presents evidence that DAP12 can suppress as well as activate natural killer (NK) cells.
16505336 Nasu-Hakola disease due to a DAP12 mutation 4.
16339517 requirement by activated and expanded CD8+ T cells for DAP12 for direct killing
16206234 Splenic mature dendritic cells from transgenic mice with DAP12 overexpression are characterized by an impaired tolerogenic potential
15356118 In clones that lack expression of KARAP/DAP12, stimulation of killer Ig-receptor KIR2DS2 does not induce cytotoxicity, whereas expression of KARAP/DAP12 is sufficient to convert a costimulatory KIR receptor into a stimulatory molecule.
14707061 DAP12 association with natural cytotoxicity receptor NKp44 is required for activating properties and surface expression of NKp44 in natural killer (NK) cells.
12925681 These results indicate an important role for DAP12-TREM2 signaling complex in the differentiation and function of osteoclasts.
12591902 CD158j in T cells functions as a costimulatory molecule through the JNK pathway independent of KARAP/DAP12 and DAP10.
12569153 DAP12 has a role in signal transduction, bone modeling, and brain myelination [review]
12207350 Myeloid abnormalities seen in KARAP/DAP12-transgenic mice indicate that KARAP/DAP12-driven signals are involved in inflammation & constitute an essential target to control resolution of inflammatory disorders based on monocytes/macrophages & neutrophils.
12080485 Mutations in two genes encoding different subunits of a receptor signaling complex (TYROBP and TREM2) result in an identical disease phenotype

AA Sequence


Text Mined References (73)

PMID Year Title
26642091 2016 Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.
26337043 2015 TREM2 in CNS homeostasis and neurodegenerative disease.
26221034 2015 Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family.
26001891 2015 Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease.
25957402 2015 DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25941351 2015 Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors.
25642940 2015 Inactivation of DAP12 in PMN inhibits TREM1-mediated activation in rheumatoid arthritis.
25487697 2015 Innate immune response is differentially dysregulated between bipolar disease and schizophrenia.
24935923 2014 Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12.
24612676 2014 C9ORF72 expansion does not affect the phenotype in Nasu-Hakola disease with the DAP12 mutation.
23810293 2013 Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival.
23715743 2013 DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells.
23561520 2013 The association of polar residues in the DAP12 homodimer: TOXCAT and molecular dynamics simulation studies.
22080356 2012 Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease.
21967868 2011 Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis.
21841309 2011 OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice.
21421043 2011 TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors.
21263069 2011 Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
20890284 2010 The structural basis for intramembrane assembly of an activating immunoreceptor complex.
20628624 2010 Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
20421649 2010 DAP12 is required for macrophage recruitment to the lung in response to cigarette smoke and chemotaxis toward CCL2.
20212065 2010 Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.
19606219 2009 Pattern of DAP12 expression in leukocytes from both healthy and systemic lupus erythematosus patients.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19120482 2009 DAP10- and DAP12-associated receptors in innate immunity.
19075187 2009 A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia.
19019460 2009 No evidence for shared etiology in two demyelinative disorders, MS and PLOSL.
17928527 2008 Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells.
17530208 2007 Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response.
17277102 2007 Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-induced inflammatory cytokine production in myeloid cells.
17202323 2007 Cutting Edge: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation.
17125796 2007 A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease.
17100880 2006 DAP12: an adapter protein with dual functionality.
17012248 2006 Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates.
16920917 2006 Molecular and functional characterization of CD300b, a new activating immunoglobulin receptor able to transduce signals through two different pathways.
16715077 2006 Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.
16505336 2006 The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16339517 2005 Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells.
16206234 2005 Enhanced tryptophan catabolism in the absence of the molecular adapter DAP12.
15557162 2004 Molecular characterization of a novel immune receptor restricted to the monocytic lineage.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15356118 2004 Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms.
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15294961 2004 A Structural basis for the association of DAP12 with mouse, but not human, NKG2D.
15057824 2004 The DNA sequence and biology of human chromosome 19.
14707061 2004 NKp44 triggers NK cell activation through DAP12 association that is not influenced by a putative cytoplasmic inhibitory sequence.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12925681 2003 DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.
12591902 2003 Selective activation of the c-Jun NH2-terminal protein kinase signaling pathway by stimulatory KIR in the absence of KARAP/DAP12 in CD4+ T cells.
12569153 2003 DAP12 signaling: from immune cells to bone modeling and brain myelination.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12426565 2002 Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D.
12426564 2002 NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation.
12370476 2002 Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms.
12207350 2002 Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice.
12080485 2002 Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.
11922939 2002 TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development.
11602640 2001 A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.
11169398 2000 Identification and molecular characterization of a natural mutant of the p50.2/KIR2DS2 activating NK receptor that fails to mediate NK cell triggering.
10940905 2000 Association of signal-regulatory proteins beta with KARAP/DAP-12.
10888890 2000 Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts.
10799849 2000 Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.
10604985 2000 Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells.
10449773 1999 Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells.
10201920 1999 Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer.
10049942 1999 NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily.
9828133 1998 Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium.
9655483 1998 Association of DAP12 with activating CD94/NKG2C NK cell receptors.
9490415 1998 Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells.
9463329 1998 Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.