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UNC13D Gene(Protein Coding)

Unc-13 Homolog D

GCID:
GC17M075827
GIFtS:
52
Genes Participants
UDN Logo

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 wtCFTR and deltaF508 traffic / Late endosome and Lysosome (norm and CF) and Innate Immune System. Gene Ontology (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

Additional gene information 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

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for UNC13D Gene

Promoters and enhancers for UNC13D Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH17I075842 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 557.3 -1.4 -1416 8.2 HDGF PKNOX1 CLOCK FOXA2 MLX ARNT ZFP64 ARID4B SIN3A DMAP1 UNC13D GC17M075847 PIR31894 FBF1 TRIM65 SRSF2 NT5C UNK NUP85 ENSG00000266980
GH17I075782 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 23 +59.7 59696 5.3 CLOCK MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 UNK GC17M075783 H3F3B MIR4738 PIR42869 SRSF2 NT5C NUP85 TRIM65 GGA3
GH17I075776 Promoter/Enhancer 2.7 UCNEbase EPDnew Ensembl ENCODE dbSUPER 9 +66.2 66191 4.9 CLOCK MLX ZFP64 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 H3F3B GC17P075777 GC17M075778 UNK NT5C SRSF2 NUP85 ENSG00000266980 GGA3 METTL23
GH17I075763 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE 8.7 +79.6 79633 2.7 HDGF PKNOX1 ARNT MLX ARID4B NEUROD1 SIN3A DMAP1 ZNF2 ZBTB7B GALK1 UBE2O FBF1 UNC13D ENSG00000267342 GC17M075747
GH17I076542 Enhancer 1.4 Ensembl ENCODE dbSUPER 11.1 -700.3 -700348 5.9 HDGF PKNOX1 FOXA2 ARNT ARID4B YBX1 ZNF2 POLR2B ZNF207 ZNF143 UNK SRSF2 ENSG00000267342 ENSG00000267543 ENSG00000266980 METTL23 ENSG00000267546 SEPT9 TRIM65 SNHG16
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around UNC13D on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the UNC13D gene promoter:

Genomic Locations for UNC13D Gene

Genomic Locations for UNC13D Gene
chr17:75,827,225-75,844,717
(GRCh38/hg38)
Size:
17,493 bases
Orientation:
Minus strand
chr17:73,823,306-73,840,798
(GRCh37/hg19)

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 Structure • Gene Density

RefSeq DNA sequence for UNC13D Gene

Proteins for UNC13D Gene

Products:

  1. Antibody
  2. Protein
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  • 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

Protein Expression for UNC13D Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for UNC13D Gene

  • Ubiquitination at isoforms=3511, posLast=599599, posLast=625625, isoforms=3714, posLast=773773, and posLast=917917

Other Protein References for UNC13D Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for UNC13D Gene

Domains & Families for UNC13D Gene

Gene Families for UNC13D Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for UNC13D Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for UNC13D Gene

GenScript: Design optimal peptide antigens:

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

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

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.

Phenotypes From GWAS Catalog for UNC13D Gene

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

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

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Vesicles (3)
See all subcellular structures

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

Products:

  1. Drug
No Compound Related Data Available

Transcripts for UNC13D Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for UNC13D Gene

(4) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(204) Selected AceView cDNA sequences:
(17) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for UNC13D Gene

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

CRISPR Products

Inhibitory RNA 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

Products:

  1. Primer

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

mRNA expression in normal human tissues for UNC13D Gene
mRNA expression by GTEx for UNC13D GenemRNA expression by BioGPS 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(2.3)

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 33 34
  • 99.24 (n)
dog
(Canis familiaris)
 Mammalia UNC13D 33 34
  • 89.44 (n)
cow
(Bos Taurus)
 Mammalia UNC13D 33 34
  • 87.88 (n)
mouse
(Mus musculus)
 Mammalia Unc13d 33 16 34
  • 86.17 (n)
rat
(Rattus norvegicus)
 Mammalia Unc13d 33
  • 85.47 (n)
oppossum
(Monodelphis domestica)
 Mammalia UNC13D 34
  • 77 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 34
  • 72 (a)
 OneToMany
-- 34
  • 53 (a)
 OneToMany
-- 34
  • 53 (a)
 OneToMany
chicken
(Gallus gallus)
 Aves UNC13D 33 34
  • 71.18 (n)
lizard
(Anolis carolinensis)
 Reptilia UNC13D 34
  • 63 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia unc13d 33
  • 62.23 (n)
zebrafish
(Danio rerio)
 Actinopterygii unc13d 33 34
  • 53.33 (n)
rainbow trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.4543 33
fruit fly
(Drosophila melanogaster)
 Insecta unc-13-4A 34
  • 23 (a)
 ManyToMany
CG34349 34
  • 21 (a)
 ManyToMany
worm
(Caenorhabditis elegans)
 Secernentea F54G2.1 34
  • 22 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 34
  • 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 Variation AA Info Type
rs111728477 uncertain-significance, Familial hemophagocytic lymphohistiocytosis 75,843,264(-) C/A 5_prime_UTR_variant, coding_sequence_variant, synonymous_variant
rs112341334 benign, uncertain-significance, not specified, Familial hemophagocytic lymphohistiocytosis 75,834,310(-) G/A/T intron_variant
rs113482537 uncertain-significance, Familial hemophagocytic lymphohistiocytosis 75,844,597(-) G/A 5_prime_UTR_variant, genic_upstream_transcript_variant, upstream_transcript_variant
rs1135688 benign, not specified, Familial hemophagocytic lymphohistiocytosis 75,831,124(-) T/C coding_sequence_variant, missense_variant
rs113861754 uncertain-significance, benign, not specified, Hemophagocytic lymphohistiocytosis, familial, 3 75,834,107(-) C/G/T coding_sequence_variant, missense_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)

Additional Variant Information 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

(10) MalaCards diseases for UNC13D Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- 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.

Additional Disease Information for UNC13D

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 HS … Seo JJ (Haematologica 2010) 3 22 58
  2. Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. (PMID: 19704116) Wood SM … Bryceson YT (Blood 2009) 3 22 58
  3. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. (PMID: 17993578) Rudd E … Henter JI (Journal of medical genetics 2008) 3 22 58
  4. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. (PMID: 18240215) Hazen MM … Binstadt BA (Arthritis and rheumatism 2008) 3 22 58
  5. Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. (PMID: 18492689) Santoro A … Aricò M (Haematologica 2008) 3 22 58

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