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Aliases for UNC13D Gene

Aliases for UNC13D Gene

  • Unc-13 Homolog D 2 3 5
  • Munc13-4 3 4
  • Unc-13 Homolog D (C. Elegans) 2
  • Protein Unc-13 Homolog D 3
  • HPLH3 3
  • FHL3 3
  • HLH3 3

External Ids for UNC13D Gene

Previous GeneCards Identifiers for UNC13D Gene

  • GC17M074420
  • GC17M071334
  • GC17M073823
  • GC17M069249

Summaries for UNC13D Gene

Entrez Gene Summary for UNC13D Gene

  • 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]

GeneCards Summary for UNC13D Gene

UNC13D (Unc-13 Homolog D) is a Protein Coding gene. Diseases associated with UNC13D include Hemophagocytic Lymphohistiocytosis, Familial, 3 and Hemophagocytic Lymphohistiocytosis. Among its related pathways are Innate Immune System and wtCFTR and deltaF508 traffic / Late endosome and Lysosome (norm and CF). GO annotations related to this gene include Rab GTPase binding. An important paralog of this gene is BAIAP3.

UniProtKB/Swiss-Prot for UNC13D Gene

  • Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.

Gene Wiki entry for UNC13D Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for UNC13D Gene

Genomics for UNC13D Gene

Regulatory Elements for UNC13D Gene

Enhancers for UNC13D Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH17G075782 1.4 ENCODE dbSUPER 23 +59.7 59697 5.3 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF548 ZNF263 UNC13D TRIM65 NUP85 UNK NT5C WBP2 ENSG00000266980 FBF1 ENSG00000267546 TMEM94
GH17G075776 2.4 ENCODE dbSUPER 8.9 +66.2 66191 4.9 MLX CREB3L1 AGO1 ZFP64 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 MRPL38 H3F3B UNK NT5C METTL23 UNC13D ENSG00000267342 TEN1 GC17M075778 GC17P075777
GH17G075821 0.9 ENCODE dbSUPER 21 +22.5 22545 1.8 NFIC PKNOX1 NFIB POLR2A AGO1 REST ZIC2 RBFOX2 UNC13D UNK WBP2 LOC100507191 GC17P075840
GH17G075737 1.7 FANTOM5 Ensembl ENCODE dbSUPER 9.8 +106.2 106217 1.4 ELF3 PKNOX1 MLX DMAP1 RAD21 THRB RARA THAP11 EGR2 ZNF263 GALK1 LLGL2 UNC13D RECQL5 GRB2 H3F3B ACOX1 SAP30BP WBP2 GGA3
GH17G076250 1.9 FANTOM5 Ensembl ENCODE dbSUPER 7.9 -407.5 -407468 3.1 HDGF PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 YY1 SLC30A9 ZNF207 RNF157 FOXJ1 JMJD6 UNC13D UBALD2 H3F3B RHBDF2 ACOX1 WBP2 ST6GALNAC2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around UNC13D on UCSC Golden Path with GeneCards custom track

Promoters for UNC13D Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000098459 817 1001 HDGF ATF1 CREB3L1 AGO1 ARID4B SIN3A DMAP1 ZBTB7B TCF12 ELK1

Genomic Location for UNC13D Gene

Chromosome:
17
Start:
75,827,225 bp from pter
End:
75,844,717 bp from pter
Size:
17,493 bases
Orientation:
Minus strand

Genomic View for UNC13D Gene

Genes around UNC13D on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
UNC13D Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for UNC13D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for UNC13D Gene

Proteins for UNC13D Gene

  • Protein details for UNC13D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q70J99-UN13D_HUMAN
    Recommended name:
    Protein unc-13 homolog D
    Protein Accession:
    Q70J99
    Secondary Accessions:
    • B4DWG9
    • Q9H7K5

    Protein attributes for UNC13D Gene

    Size:
    1090 amino acids
    Molecular mass:
    123282 Da
    Quaternary structure:
    • Interacts with DOC2A (By similarity). Interacts with RAB27A.
    SequenceCaution:
    • Sequence=BAB15764.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for UNC13D Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for UNC13D Gene

Post-translational modifications for UNC13D Gene

  • Ubiquitination at Lys511, Lys599, Lys625, Lys714, posLast=773773, and posLast=917917
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for UNC13D Gene

Domains & Families for UNC13D Gene

Gene Families for UNC13D Gene

Suggested Antigen Peptide Sequences for UNC13D Gene

Graphical View of Domain Structure for InterPro Entry

Q70J99

UniProtKB/Swiss-Prot:

UN13D_HUMAN :
  • The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome.
  • Belongs to the unc-13 family.
Domain:
  • The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome.
Family:
  • Belongs to the unc-13 family.
genes like me logo Genes that share domains with UNC13D: view

Function for UNC13D Gene

Molecular function for UNC13D Gene

UniProtKB/Swiss-Prot Function:
Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.

Gene Ontology (GO) - Molecular Function for UNC13D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15548590
GO:0017137 Rab GTPase binding IPI 22899725
genes like me logo Genes that share ontologies with UNC13D: view
genes like me logo Genes that share phenotypes with UNC13D: view

Human Phenotype Ontology for UNC13D Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for UNC13D Gene

MGI Knock Outs for UNC13D:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for UNC13D Gene

Localization for UNC13D Gene

Subcellular locations from UniProtKB/Swiss-Prot for UNC13D Gene

Cytoplasm. Membrane; Peripheral membrane protein. Late endosome. Recycling endosome. Lysosome. Note=Colocalizes with cytotoxic granules at the plasma membrane. Localizes to endosomal exocytic vesicles.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for UNC13D gene
Compartment Confidence
cytosol 5
lysosome 5
endosome 5
extracellular 4
nucleus 3
endoplasmic reticulum 3
plasma membrane 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for UNC13D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005737 cytoplasm IEA --
GO:0005764 lysosome IEA,IDA 15548590
GO:0005768 endosome IEA --
GO:0005770 late endosome IEA --
genes like me logo Genes that share ontologies with UNC13D: view

Pathways & Interactions for UNC13D Gene

genes like me logo Genes that share pathways with UNC13D: view

Pathways by source for UNC13D Gene

3 Reactome pathways for UNC13D Gene
1 GeneGo (Thomson Reuters) pathway for UNC13D Gene

Gene Ontology (GO) - Biological Process for UNC13D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002432 granuloma formation IEA --
GO:0002467 germinal center formation IEA --
GO:0006887 exocytosis IEA --
GO:0006909 phagocytosis IEA --
GO:0043304 regulation of mast cell degranulation IMP 15548590
genes like me logo Genes that share ontologies with UNC13D: view

No data available for SIGNOR curated interactions for UNC13D Gene

Drugs & Compounds for UNC13D Gene

No Compound Related Data Available

Transcripts for UNC13D Gene

Unigene Clusters for UNC13D Gene

Unc-13 homolog D (C. elegans):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for UNC13D Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^
SP1:
SP2: -

ExUns: 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31
SP1:
SP2:

Relevant External Links for UNC13D Gene

GeneLoc Exon Structure for
UNC13D
ECgene alternative splicing isoforms for
UNC13D

Expression for UNC13D Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for UNC13D Gene

mRNA differential expression in normal tissues according to GTEx for UNC13D Gene

This gene is overexpressed in Whole Blood (x17.3) and Spleen (x4.4).

Protein differential expression in normal tissues from HIPED for UNC13D Gene

This gene is overexpressed in Peripheral blood mononuclear cells (35.9), Platelet (8.5), and Monocytes (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for UNC13D Gene



Protein tissue co-expression partners for UNC13D Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of UNC13D Gene:

UNC13D

SOURCE GeneReport for Unigene cluster for UNC13D Gene:

Hs.41045

mRNA Expression by UniProt/SwissProt for UNC13D Gene:

Q70J99-UN13D_HUMAN
Tissue specificity: Expressed at high levels in spleen, thymus and leukocytes. Also expressed in lung and placenta, and at very low levels in brain, heart, skeletal muscle and kidney. Expressed in cytotoxic T-lymphocytes (CTL) and mast cells.

Evidence on tissue expression from TISSUES for UNC13D Gene

  • Blood(4.6)
  • Spleen(4.3)
  • Liver(4.2)
  • Pancreas(4.2)
  • Bone marrow(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for UNC13D Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Organs:
Head and neck:
  • brain
  • cerebrospinal fluid
  • ear
  • eye
  • head
  • meninges
  • mouth
  • neck
  • skull
Thorax:
  • heart
  • lung
Abdomen:
  • biliary tract
  • duodenum
  • intestine
  • liver
  • pancreas
  • small intestine
  • spleen
Limb:
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • lymph node
  • red blood cell
  • skin
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with UNC13D: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for UNC13D Gene

Orthologs for UNC13D Gene

This gene was present in the common ancestor of animals.

Orthologs for UNC13D Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia UNC13D 34 35
  • 99.24 (n)
dog
(Canis familiaris)
Mammalia UNC13D 34 35
  • 89.44 (n)
cow
(Bos Taurus)
Mammalia UNC13D 34 35
  • 87.88 (n)
mouse
(Mus musculus)
Mammalia Unc13d 34 16 35
  • 86.17 (n)
rat
(Rattus norvegicus)
Mammalia Unc13d 34
  • 85.47 (n)
oppossum
(Monodelphis domestica)
Mammalia UNC13D 35
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 72 (a)
OneToMany
-- 35
  • 53 (a)
OneToMany
-- 35
  • 53 (a)
OneToMany
chicken
(Gallus gallus)
Aves UNC13D 34 35
  • 71.18 (n)
lizard
(Anolis carolinensis)
Reptilia UNC13D 35
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia unc13d 34
  • 62.23 (n)
zebrafish
(Danio rerio)
Actinopterygii unc13d 34 35
  • 53.33 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4543 34
fruit fly
(Drosophila melanogaster)
Insecta unc-13-4A 35
  • 23 (a)
ManyToMany
CG34349 35
  • 21 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea F54G2.1 35
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 24 (a)
OneToMany
Species where no ortholog for UNC13D was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for UNC13D Gene

ENSEMBL:
Gene Tree for UNC13D (if available)
TreeFam:
Gene Tree for UNC13D (if available)

Paralogs for UNC13D Gene

Paralogs for UNC13D Gene

(2) SIMAP similar genes for UNC13D Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with UNC13D: view

Variants for UNC13D Gene

Sequence variations from dbSNP and Humsavar for UNC13D Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs121434352 Pathogenic 75,840,317(-) GCTGC(C/G/T)GAGAG reference, missense, stop-gained
rs121434353 Pathogenic 75,836,662(-) CCTGC(C/T)GACCT reference, missense
rs121434354 Pathogenic 75,831,153(-) CTGCT(G/T)CCACG reference, missense
rs201908137 Pathogenic 75,840,506(+) CCTCA(A/C)CTGCA splice-donor-variant
rs777759523 Pathogenic 75,836,338(+) CCATA(C/T)CTGCA splice-donor-variant

Structural Variations from Database of Genomic Variants (DGV) for UNC13D Gene

Variant ID Type Subtype PubMed ID
nsv470606 CNV loss 18288195
nsv478765 CNV novel sequence insertion 20440878
nsv510728 CNV deletion 20534489
nsv833545 CNV gain 17160897

Variation tolerance for UNC13D Gene

Residual Variation Intolerance Score: 57.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.81; 83.43% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for UNC13D Gene

Human Gene Mutation Database (HGMD)
UNC13D
SNPedia medical, phenotypic, and genealogical associations of SNPs for
UNC13D

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for UNC13D Gene

Disorders for UNC13D Gene

MalaCards: The human disease database

(12) MalaCards diseases for UNC13D Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hemophagocytic lymphohistiocytosis, familial, 3
  • familial hemophagocytic lymphohistiocytosis 3
hemophagocytic lymphohistiocytosis
  • haemophagocytic syndrome
lymphatic system disease
  • adenopathy
griscelli syndrome, type 2
  • griscelli syndrome type 2
macrophage activation syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

UN13D_HUMAN
  • Familial hemophagocytic lymphohistiocytosis 3 (FHL3) [MIM:608898]: A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. {ECO:0000269 PubMed:14622600}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for UNC13D

Genetic Association Database (GAD)
UNC13D
Human Genome Epidemiology (HuGE) Navigator
UNC13D
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
UNC13D
genes like me logo Genes that share disorders with UNC13D: view

No data available for Genatlas for UNC13D Gene

Publications for UNC13D Gene

  1. UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis. (PMID: 20015888) Yoon H.S. … Seo J.J. (Haematologica 2010) 3 22 64
  2. Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. (PMID: 19704116) Wood S.M. … Bryceson Y.T. (Blood 2009) 3 22 64
  3. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. (PMID: 17993578) Rudd E. … Henter J.I. (J. Med. Genet. 2008) 3 22 64
  4. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. (PMID: 18240215) Hazen M.M. … Binstadt B.A. (Arthritis Rheum. 2008) 3 22 64
  5. Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. (PMID: 18492689) Santoro A. … AricA^ M. (Haematologica 2008) 3 22 64

Products for UNC13D Gene

Sources for UNC13D Gene

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