Property Summary

NCBI Gene PubMed Count 52
PubMed Score 80.21
PubTator Score 91.20

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -1.141 2.1e-04
non primary Sjogren syndrome sicca 1.100 2.1e-02
lung carcinoma -1.200 5.2e-20

 GO Function (1)

Gene RIF (43)

PMID Text
26637356 Data (including data from studies in knockout mice) suggest Munc13-4 binds to Rab11 and regulates trafficking of Rab11-containing vesicles; Munc13-4 appears to regulate final steps of Rab11-positive vesicle docking at plasma membrane in exocytosis.
26637270 Munc13-4 conveys Ca(2+) sensitivity to platelet SNARE-mediated membrane fusion and reveal a potential mechanism by which Munc13-4 bridges and stabilizes apposing membranes destined for fusion.
25980904 Synergistic defects of UNC13D and AP3B1 leading to adult hemophagocytic lymphohistiocytosis.
25573973 These data support an important role for Munc13-4 in human platelet degranulation
25312756 These studies highlight the need for RAB27A sequencing in patients with FHL with normal pigmentation and identify a critical binding site for Munc13-4 on Rab27a, revealing the molecular basis of this interaction.
24842371 Data indicate that Munc13-4 is highly expressed in differentiated NK cells and effector CD8(+) T lymphocytes.
24470399 The prevalence of a 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in UNC13D was determined in 1709 North American patients with type 3 hemophagocytic lymphohistiocytosis. 8 new mutations were also found.
24043286 This patient the patient carried mutations in FAS, XIAP, and UNC13D genes inherited from his mother who had rheumatoid arthritis; UNC13D is involved in familial hemophagocytic lymphohistiocytosis
23924873 this is the first report of HLH in association with EVC syndrome, and the IVS13+5G>A mutation that we believe is causative of EVC in our patient is also unreported.
23840885 These data suggest that rare loss-of-function variations of UND13D are risk factors for autoimmune lymphoproliferative syndrome development.
23810987 Defects in cargo trafficking caused by mutations in RAB27A and UNC13D genes, encoding Rab27a and its effector Munc13-4, cause severe immunodeficiencies in humans. (Review)
23672263 Novel deep intronic and missense UNC13D mutations are reported in familial haemophagocytic lymphohistiocytosis type 3.
23180437 The deep intronic mutation UNC13D:c.118-308C>T accounts for the majority of previously missing mutations and is the most frequent mutation in familial hemophagocytic lymphohistiocytosis type 3 in Korea.
22508512 study reports that Munc13-4 bound Ca(2 ) and restored Ca(2 )-dependent granule exocytosis to permeable cells (platelets, mast, and neuroendocrine cells) dependent on putative Ca(2 )-binding residues in C2A and C2B.
22271450 Data indicate that Munc13-4 reinternalization is required for the maintenance of an intracellular pool that is functional to guarantee the serial killing potential.
21931115 Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D.
21881043 Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%).
21755595 novel Dutch founder mutation leads to severe early onset of FHL3 due to misfolding and degradation of munc13-4(1-899).
21693760 Data show that point mutations in the binding motif of munc13-4 have severely impaired rab27a binding, allowing dissection of rab27a requirements in munc13-4 function.
21674762 Seven novel mutations in PRF1, UNC13D, and XIAP were identified in Chinese EBV-HLH patients. Only a fraction of Chinese children with EBV-HLH have genetic defects in PRF1, UNC13D, and XIAP.
21646258 study reports recurrent fetal hydrops caused by familial hemophagocytic lymphohistiocytosis with Munc13-4 mutation
21370424 Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia.
20823128 Data show that all but one patient with atypical familial hemophagocytic lymphohistiocytosis carried at least one splice-site mutation in UNC13D or STXBP2.
20015888 rRecurrent splicing mutations in UNC13D gene is associated with familial hemophagocytic lymphohistiocytosis.
19704116 Rab27a or Munc13-4 recruitment to lytic granules is preferentially regulated by different receptor signals, demonstrating that individual target cell ligands regulate discrete molecular events for lytic granule maturation.
19131769 UNC13D mutations are associated with primary hemophagocytic lymphohistiocytosis.
19120489 mutated in type III hemophagocytic lymphohistiocytosis, a severe inflammatory disease of infectious etiology with fatal outcome
18759271 The data suggest an association between MUNC13-4 polymorphisms and macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis.
18759271 Observational study of gene-disease association. (HuGE Navigator)
18710388 Observational study of gene-disease association. (HuGE Navigator)
18492689 UNC13D mutations leading to splicing errors represent the majority of mutations observed in familial hemophagocytic lymphohistiocytosis
18453599 a role for Munc13-4 as a component of the secretory machinery in neutrophils.
18432499 Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations
18311812 The genes PRF1, GZMB, UNC13D, and Rab27a involved in hemophagocytic lymphohistiocytosis do not confer a significant risk of association with systemic-onset juvenile idiopathic arthritis.
18311812 Observational study of gene-disease association. (HuGE Navigator)
18240215 girl with systemic juvenile arthritis without macrophage activation syndrome was found to have compound heterozygous mutations of UNC13D and reduced NK cell cytotoxic function
17993578 Biallelic UNC13D mutations were found in 18% of the PRF1/STX11-negative familial haemophagocytic lymphohistiocytosis families.
16825436 12 novel and 4 known Munc13-4 mutations spread throughout the gene were found in haemophagocytic lymphohistiocytosis patients.
16778144 CD107a surface expression has a role in Munc13-4 defect in familial hemophagocytic lymphohistiocytosis
16630545 These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins.
16278825 A large group of 63 unrelated patients with Familial hemophagocytic lymphohistiocytosis (FHL) was analysed for mutations in STX11, PRF1, and UNC13D.
14699162 Rab27 regulates the dense core granule secretion in platelets by employing its binding protein, Munc13-4
14622600 HMunc13-4 mutations were shown to cause familial hemophagocytic lymphohistiocytosis; HMunc13-4 is essential for the priming step of cytolytic granules secretion preceding vesicle membrane fusion.

AA Sequence

MATLLSHPQQRPPFLRQAIKIRRRRVRDLQDPPPQMAPEIQPPSHHFSPEQRALLYEDALYTVLHRLGHP      1 - 70
EPNHVTEASELLRYLQEAFHVEPEEHQQTLQRVRELEKPIFCLKATVKQAKGILGKDVSGFSDPYCLLGI     71 - 140
EQGVGVPGGSPGSRHRQKAVVRHTIPEEETHRTQVITQTLNPVWDETFILEFEDITNASFHLDMWDLDTV    141 - 210
ESVRQKLGELTDLHGLRRIFKEARKDKGQDDFLGNVVLRLQDLRCREDQWYPLEPRTETYPDRGQCHLQF    211 - 280
QLIHKRRATSASRSQPSYTVHLHLLQQLVSHEVTQHEAGSTSWDGSLSPQAATVLFLHATQKDLSDFHQS    281 - 350
MAQWLAYSRLYQSLEFPSSCLLHPITSIEYQWIQGRLKAEQQEELAASFSSLLTYGLSLIRRFRSVFPLS    351 - 420
VSDSPARLQSLLRVLVQMCKMKAFGELCPNTAPLPQLVTEALQTGTTEWFHLKQQHHQPMVQGIPEAGKA    421 - 490
LLGLVQDVIGDLHQCQRTWDKIFHNTLKIHLFSMAFRELQWLVAKRVQDHTTVVGDVVSPEMGESLFQLY    491 - 560
ISLKELCQLRMSSSERDGVLALDNFHRWFQPAIPSWLQKTYNEALARVQRAVQMDELVPLGELTKHSTSA    561 - 630
VDLSTCFAQISHTARQLDWPDPEEAFMITVKFVEDTCRLALVYCSLIKARARELSSGQKDQGQAANMLCV    631 - 700
VVNDMEQLRLVIGKLPAQLAWEALEQRVGAVLEQGQLQNTLHAQLQSALAGLGHEIRTGVRTLAEQLEVG    701 - 770
IAKHIQKLVGVRESVLPEDAILPLMKFLEVELCYMNTNLVQENFSSLLTLLWTHTLTVLVEAAASQRSSS    771 - 840
LASNRLKIALQNLEICFHAEGCGLPPKALHTATFQALQRDLELQAASSRELIRKYFCSRIQQQAETTSEE    841 - 910
LGAVTVKASYRASEQKLRVELLSASSLLPLDSNGSSDPFVQLTLEPRHEFPELAARETQKHKKDLHPLFD    911 - 980
ETFEFLVPAEPCRKAGACLLLTVLDYDTLGADDLEGEAFLPLREVPGLSGSEEPGEVPQTRLPLTYPAPN    981 - 1050
GDPILQLLEGRKGDREAQVFVRLRRHRAKQASQHALRPAP                                 1051 - 1090
//

Text Mined References (59)

PMID Year Title
26637356 2016 Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.
26637270 2016 Role of Munc13-4 as a Ca2+-dependent tether during platelet secretion.
26627825 2016 Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus aureus Inhibits the Formation of Platelet-Leukocyte Complexes.
25980904 2015 Synergistic defects of UNC13D and AP3B1 leading to adult hemophagocytic lymphohistiocytosis.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25573973 2015 First characterization of platelet secretion defect in patients with familial hemophagocytic lymphohistiocytosis type 3 (FHL-3).
25312756 2015 Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding.
24842371 2014 Transcriptional regulation of Munc13-4 expression in cytotoxic lymphocytes is disrupted by an intronic mutation associated with a primary immunodeficiency.
24470399 2014 The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24043286 2013 Mutation of FAS, XIAP, and UNC13D genes in a patient with a complex lymphoproliferative phenotype.
23924873 2013 A novel mutation, IVS13+5G>A, in Ellis-van Creveld syndrome associated with haemophagocytic lymphohistiocytosis.
23840885 2013 Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome.
23810987 2013 Evidence for defective Rab GTPase-dependent cargo traffic in immune disorders.
23672263 2013 Novel deep intronic and missense UNC13D mutations in familial haemophagocytic lymphohistiocytosis type 3.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23180437 2013 Founder effects in two predominant intronic mutations of UNC13D, c.118-308C>T and c.754-1G>C underlie the unusual predominance of type 3 familial hemophagocytic lymphohistiocytosis (FHL3) in Korea.
22899725 2012 A complete Rab screening reveals novel insights in Weibel-Palade body exocytosis.
22508512 2012 Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion.
22271450 2012 PIP2-dependent regulation of Munc13-4 endocytic recycling: impact on the cytolytic secretory pathway.
21931115 2011 Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D.
21881043 2011 Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH.
21755595 2012 A novel Dutch mutation in UNC13D reveals an essential role of the C2B domain in munc13-4 function.
21693760 2011 The munc13-4-rab27 complex is specifically required for tethering secretory lysosomes at the plasma membrane.
21674762 2012 Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
21646258 2011 Hemophagocytic lymphohistiocytosis with Munc13-4 mutation: a cause of recurrent fatal hydrops fetalis.
21370424 2011 Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia.
21269460 2011 Initial characterization of the human central proteome.
20823128 2010 Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases.
20015888 2010 UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis.
19966785 2010 Rab27a and Rab27b control different steps of the exosome secretion pathway.
19704116 2009 Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity.
19131769 2008 Neonatal primary hemophagocytic lymphohistiocytosis in Turkish children.
19120489 2009 Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases.
18759271 2008 Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms.
18710388 2008 Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18492689 2008 Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3.
18453599 2008 Munc13-4 regulates granule secretion in human neutrophils.
18432499 Fatal sibling cases of familial hemophagocytic lymphohistiocytosis (FHL) with MUNC13-4 mutations: case reports.
18311812 2008 Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis.
18240215 2008 Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis.
17993578 2008 Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis.
17237785 2007 Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16825436 2006 Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis.
16778144 2006 Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease.
16630545 2006 Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism.
16625196 2006 DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.
16278825 2006 Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A.
15548590 2005 Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15466010 2004 Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14699162 2004 Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets.
14622600 2003 Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11214971 2000 Characterization of long cDNA clones from human adult spleen.