U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 201294, updated on 12-Nov-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. Rudd E, et al. J Med Genet, 2008 Mar. PMID 17993578
  2. 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
  3. 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
  4. 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
  5. A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication. Balcı YI, et al. Turk J Haematol, 2015 Dec. PMID 26377049, Free PMC Article

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

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
Preferred Names
protein unc-13 homolog D

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous