TYROBP (transmembrane immune signaling adaptor TYROBP)

Gene

• Entrez ID: 7305
• Gene name: Transmembrane immune signaling adaptor TYROBP
• Gene symbol: TYROBP
• Synonyms: DAP12, KARAP, PLOSL, PLOSL1
• Chromosome: 19
• Chromosome location: 19q13.12
• Summary: This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs55746266	C>G	Benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs104894732	A>G	Pathogenic	Initiator codon variant, non coding transcript variant, missense variant
rs386833839	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs386833840	C>-	Pathogenic-likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs386833841	C>G	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs386833842	C>A,T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002222	Process	Stimulatory killer cell immunoglobulin-like receptor signaling pathway	IDA	9655483
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	IDA	9655483
GO:0002274	Process	Myeloid leukocyte activation	IDA	10604985
GO:0002282	Process	Microglial cell activation involved in immune response	IBA	21873635
GO:0002282	Process	Microglial cell activation involved in immune response	ISS
GO:0002283	Process	Neutrophil activation involved in immune response	IBA	21873635
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005102	Function	Signaling receptor binding	IPI	11602640, 15294961
GO:0005102	Function	Signaling receptor binding	ISS	29518356
GO:0005102	Function	Signaling receptor binding	TAS	15601948
GO:0005515	Function	Protein binding	IPI	9655483, 10049942, 10940905, 11602640, 14707061, 18624290, 26221034, 28100677, 28490631, 32296183
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IDA	9655483
GO:0006968	Process	Cellular defense response	TAS	9490415
GO:0007165	Process	Signal transduction	TAS	9490415
GO:0009986	Component	Cell surface	IBA	21873635
GO:0009986	Component	Cell surface	IDA	15294961
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0016021	Component	Integral component of membrane	TAS	15601948
GO:0030036	Process	Actin cytoskeleton organization	ISS
GO:0030316	Process	Osteoclast differentiation	IMP	21841309
GO:0030667	Component	Secretory granule membrane	TAS
GO:0030889	Process	Negative regulation of B cell proliferation	IBA	21873635
GO:0030889	Process	Negative regulation of B cell proliferation	IMP	21727189
GO:0030900	Process	Forebrain development	ISS
GO:0032693	Process	Negative regulation of interleukin-10 production	ISS
GO:0032731	Process	Positive regulation of interleukin-1 beta production	ISS
GO:0032755	Process	Positive regulation of interleukin-6 production	ISS
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS
GO:0032816	Process	Positive regulation of natural killer cell activation	IBA	21873635
GO:0032911	Process	Negative regulation of transforming growth factor beta1 production	IBA	21873635
GO:0032911	Process	Negative regulation of transforming growth factor beta1 production	ISS
GO:0032930	Process	Positive regulation of superoxide anion generation	ISS
GO:0034241	Process	Positive regulation of macrophage fusion	IBA	21873635
GO:0034241	Process	Positive regulation of macrophage fusion	IMP	18957693
GO:0035556	Process	Intracellular signal transduction	TAS	9490415
GO:0042802	Function	Identical protein binding	IPI	20890284
GO:0042803	Function	Protein homodimerization activity	IDA	9655483
GO:0043277	Process	Apoptotic cell clearance	ISS
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0045087	Process	Innate immune response	TAS
GO:0046872	Function	Metal ion binding	IEA
GO:0048678	Process	Response to axon injury	ISS
GO:0050776	Process	Regulation of immune response	TAS
GO:0050821	Process	Protein stabilization	IDA	25957402
GO:0050821	Process	Protein stabilization	IMP	23715743
GO:0097190	Process	Apoptotic signaling pathway	ISS
GO:0110090	Process	Positive regulation of hippocampal neuron apoptotic process	ISS
GO:1900272	Process	Negative regulation of long-term synaptic potentiation	ISS
GO:1901216	Process	Positive regulation of neuron death	ISS
GO:1902685	Process	Positive regulation of receptor localization to synapse	ISS
GO:1904151	Process	Positive regulation of microglial cell mediated cytotoxicity	IBA	21873635
GO:1904151	Process	Positive regulation of microglial cell mediated cytotoxicity	ISS
GO:2000010	Process	Positive regulation of protein localization to cell surface	IMP	23715743
GO:2001206	Process	Positive regulation of osteoclast development	ISS

Other IDs

• MIM: 604142
• HGNC: 12449
• e!Ensembl: ENSG00000011600

Protein

• UniProt ID: O43914
• Protein name: TYRO protein tyrosine kinase-binding protein (DNAX-activation protein 12) (Killer-activating receptor-associated protein) (KAR-associated protein)
• Protein function: Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:10604985, PubMed:9490415, PubM
• PDB: 2L34, 2L35, 4WO1, 4WOL, 7Q5W
• Sequence:

  MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSPGVLAGIVMGDLVLTVLIALA
  VYFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRPYYK

• Sequence length: 113

Pathways

KEGG:

Osteoclast differentiation
Natural killer cell mediated cytotoxicity

Reactome:

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
DAP12 interactions
DAP12 signaling
Signal regulatory protein family interactions
Other semaphorin interactions
Neutrophil degranulation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Apraxia	Apraxias	rs121908377, rs121908378, rs1135401820, rs1178491246, rs1584969672
Developmental regression	Developmental regression	rs1224421127
Hydrocephalus	Hydrocephalus	rs387907320, rs369384363, rs387907321, rs372127610, rs770273135, rs797045095, rs797045707, rs769795916, rs781251438, rs922703465, rs376078512, rs1567043467, rs1587149916, rs1586841546
Leukemia	Acute leukemia	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601
Leukoencephalopathy	Leukoencephalopathy	rs34757931
Osteochondrodysplasia	Osteochondrodysplasias	rs386833498, rs104893919, rs104893916, rs386833492, rs121908078, rs386833497, rs386833507, rs200963884, rs121908077, rs786204675, rs763198695, rs1554095433, rs766836061
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy	POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY, POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 1	rs104893998, rs104894001, rs121908402, rs104894002, rs104894732, rs386833839, rs386833840, rs386833842, rs386834140, rs386834141, rs386834142, rs386834143, rs386834144, rs201258663, rs797044603	12370476, 10888890, 24357685
Skeletal dysplasia	Skeletal dysplasia	rs121912632, rs121912633, rs121912634, rs121912636, rs121912637, rs267607147, rs387906324, rs267607150, rs397514473, rs398123438, rs515726153, rs515726154, rs515726162, rs515726163, rs515726172, rs757011098

Unknown
Disease name	Disease term	dbSNP ID	References
Agnosia	Agnosia
Cerebral atrophy	Cerebral atrophy
Cerebral cortical atrophy	Cerebral cortical atrophy
Dementia	Dementia		10888890, 15049507
Dementia of frontal lobe	Dementia of frontal lobe type
Hypoplasia of corpus callosum	Hypoplasia of corpus callosum
Nasu-hakola disease	Nasu-Hakola disease
Oculomotor apraxia	Oculomotor apraxia
Oculovestibuloauditory syndrome	Oculovestibuloauditory syndrome
Speech disorders	Speech Disorders