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    UNC13D unc-13 homolog D [ Homo sapiens (human) ]

    Gene ID: 201294, updated on 5-Nov-2024

    Summary

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    Official Symbol
    UNC13Dprovided by HGNC
    Official Full Name
    unc-13 homolog Dprovided by HGNC
    Primary source
    HGNC:HGNC:23147
    See related
    Ensembl:ENSG00000092929 MIM:608897; AllianceGenome:HGNC:23147
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FHL3; HLH3; HPLH3; Munc13-4
    Summary
    This gene encodes a protein that is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other Munc13 proteins. The protein appears to play a role in vesicle maturation during exocytosis and is involved in regulation of cytolytic granules secretion. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis type 3, a genetically heterogeneous, rare autosomal recessive disorder. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in bone marrow (RPKM 20.9), lung (RPKM 16.7) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UNC13D in Genome Data Viewer
    Location:
    17q25.1
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (75827225..75844404, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (76720377..76737555, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (73823306..73840485, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73780981-73781559 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73781560-73782137 Neighboring gene microRNA 4738 Neighboring gene unk zinc finger Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73810697-73811198 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73811199-73811698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73812483-73812984 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73812985-73813484 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73825830-73826818 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73826819-73827806 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73831316-73831816 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73832318-73833318 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73834667-73835166 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8986 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73840002-73840706 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8988 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12779 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12781 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8989 Neighboring gene WW domain binding protein 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:73852240-73853035 Neighboring gene Sharpr-MPRA regulatory region 12387 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73861034-73861534 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73864718-73865644 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:73872205-73873120 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73873121-73874036 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:73874037-73874952 Neighboring gene tripartite motif containing 47

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. 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. Seo JY, et al. Ann Hematol, 2013 Mar. PMID 23180437
    2. Identification of a novel nonsense mutation in the UNC13D gene from a patient with hemophagocytic lymphohistiocytosis: a case report. Hu X, et al. BMC Med Genet, 2018 May 21. PMID 29783935, Free PMC Article
    3. Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: Molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP. Chen X, et al. Clin Genet, 2018 Aug. PMID 29665027
    4. Human CTL-based functional analysis shows the reliability of a munc13-4 protein expression assay for FHL3 diagnosis. Shibata H, et al. Blood, 2018 May 3. PMID 29549174
    5. Gene-corrected human Munc13-4-deficient CD8+ T cells can efficiently restrict EBV-driven lymphoproliferation in immunodeficient mice. Soheili T, et al. Blood, 2016 Dec 15. PMID 27799161

    See all (90) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Functional role of UNC13D in immune diseases and its therapeutic applications.
      Title: Functional role of UNC13D in immune diseases and its therapeutic applications.
    2. Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.
      Title: Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.
    3. Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis.
      Title: Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis.
    4. Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
      Title: Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
    5. Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused by UNC13D Genetic Defects.
      Title: Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused by UNC13D Genetic Defects.
    6. Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.
      Title: Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.
    7. Alternative UNC13D Promoter Encodes a Functional Munc13-4 Isoform Predominantly Expressed in Lymphocytes and Platelets.
      Title: Alternative UNC13D Promoter Encodes a Functional Munc13-4 Isoform Predominantly Expressed in Lymphocytes and Platelets.
    8. Different Clinical Presentation of 3 Children With Familial Hemophagocytic Lymphohistiocytosis With 2 Novel Mutations.
      Title: Different Clinical Presentation of 3 Children With Familial Hemophagocytic Lymphohistiocytosis With 2 Novel Mutations.
    9. Defective Zn(2+) homeostasis in mouse and human platelets with alpha- and delta-storage pool diseases.
      Title: Defective Zn(2+) homeostasis in mouse and human platelets with α- and δ-storage pool diseases.
    10. Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency.
      Title: Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency.
    Submit: New GeneRIF Correction See all GeneRIFs (64)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Familial hemophagocytic lymphohistiocytosis 3
    MedGen: C1837174 OMIM: 608898 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in defense response to virus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in germinal center formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in granuloma formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in natural killer cell degranulation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phagocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of exocytosis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of regulated secretory pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of substrate adhesion-dependent cell spreading IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of mast cell degranulation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in Weibel-Palade body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in azurophil granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in exocytic vesicle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in exocytic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in late endosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in recycling endosome IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein unc-13 homolog D

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007266.1 RefSeqGene

      Range
      5001..22493
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_122

    mRNA and Protein(s)

    1. NM_199242.3 → NP_954712.1  protein unc-13 homolog D

      See identical proteins and their annotated locations for NP_954712.1

      Status: REVIEWED

      Source sequence(s)
      AC087289
      Consensus CDS
      CCDS11730.1
      UniProtKB/Swiss-Prot
      B4DWG9, Q70J99, Q9H7K5
      Related
      ENSP00000207549.3, ENST00000207549.9
      Conserved Domains (3) summary
      cd04009
      Location:910 → 1039
      C2B_Munc13-like; C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins
      cd08676
      Location:84 → 263
      C2A_Munc13-like; C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins
      pfam10540
      Location:790 → 891
      Membr_traf_MHD; Munc13 (mammalian uncoordinated) homology domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      75827225..75844404 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      76720377..76737555 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q70J99.1 GenPept UniProtKB/Swiss-Prot:Q70J99

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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