This gene encodes a DENN-domain-containing protein that functions as a RAB-activating guanine nucleotide exchange factor (GEF). This protein catalyzes the conversion of GDP to GTP and thereby converts inactive GDP-bound Rab proteins into their active GTP-bound form. The encoded protein is recruited by RAB6 onto Golgi membranes and is therefore referred to as RAB6-interacting pr... See more...

Aliases for DENND5A Gene

Aliases for DENND5A Gene

  • DENN Domain Containing 5A 2 3 5
  • DENN Domain-Containing Protein 5A 3 4
  • DENN/MADD Domain Containing 5A 2 3
  • RAB6 Interacting Protein 1 2 3
  • Rab6-Interacting Protein 1 3 4
  • KIAA1091 2 4
  • RAB6IP1 3 4
  • FLJ22354 2
  • FLJ33829 2
  • FLJ43455 2
  • DENND5A 5
  • Rab6IP1 4
  • EIEE49 3

External Ids for DENND5A Gene

Previous HGNC Symbols for DENND5A Gene

  • RAB6IP1

Previous GeneCards Identifiers for DENND5A Gene

  • GC11M009117
  • GC11M008832

Summaries for DENND5A Gene

Entrez Gene Summary for DENND5A Gene

  • This gene encodes a DENN-domain-containing protein that functions as a RAB-activating guanine nucleotide exchange factor (GEF). This protein catalyzes the conversion of GDP to GTP and thereby converts inactive GDP-bound Rab proteins into their active GTP-bound form. The encoded protein is recruited by RAB6 onto Golgi membranes and is therefore referred to as RAB6-interacting protein 1. This protein binds with RAB39 as well. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene are associated with early infantile epileptic encephalopathy-49. [provided by RefSeq, Feb 2017]

GeneCards Summary for DENND5A Gene

DENND5A (DENN Domain Containing 5A) is a Protein Coding gene. Diseases associated with DENND5A include Epileptic Encephalopathy, Early Infantile, 49 and Encephalopathy. Among its related pathways are RAB GEFs exchange GTP for GDP on RABs and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include Rab GTPase binding and Rab guanyl-nucleotide exchange factor activity. An important paralog of this gene is DENND5B.

UniProtKB/Swiss-Prot Summary for DENND5A Gene

  • Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DENND5A Gene

Genomics for DENND5A Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DENND5A 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
GH11J009263 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 607.9 +1.1 1149 4.8 CREB1 GATAD2A ATF7 ZNF629 KDM1A ZNF692 POLR2A BACH1 JUND LARP7 DENND5A lnc-IPO7-4 TMEM41B SCUBE2 piR-55985-021
GH11J009361 Promoter/Enhancer 1.9 FANTOM5 ENCODE CraniofacialAtlas 31.6 -98.2 -98166 4.9 HNRNPL CREB1 GATAD2A TEAD4 PRDM10 REST ZNF629 TFE3 ZNF512 LEF1 lnc-TMEM41B-10 lnc-IPO7-2 NRIP3 DENND5A SNORA3B ZNF143 AKIP1 RPL21P97 RPL27A IPO7
GH11J009273 Enhancer 0.8 FANTOM5 ENCODE 36.1 -8.5 -8491 0.9 PKNOX1 SCRT2 CEBPB SPI1 ATF4 CEBPG MEIS2 POLR2A TRL-CAA5-1 piR-50443-058 DENND5A NRIP3 TMEM41B SCUBE2 ZNF143 IPO7 TMEM9B
GH11J009001 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE 14.8 +262.1 262127 3.3 RNF2 PRDM10 JUND PKNOX1 POLR2A ZNF24 EZH2 FUS ZNF341 GATAD2B NRIP3 ENSG00000253973 LOC105376541 SCUBE2 AKIP1 DENND5A TMEM9B ZNF143 IPO7 HSALNG0082586
GH11J009158 Enhancer 0.8 FANTOM5 ENCODE 32.3 +105.3 105316 2.2 CEBPB JUN RBM22 JUND FOSL1 CEBPG ATF4 ATF3 DENND5A NRIP3 SCUBE2 TMEM41B ZNF143 IPO7 TMEM9B RPL27A lnc-SCUBE2-2 lnc-SCUBE2-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DENND5A on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DENND5A

Top Transcription factor binding sites by QIAGEN in the DENND5A gene promoter:
  • Arnt
  • c-Myc
  • ER-alpha
  • GR
  • GR-alpha
  • GR-beta
  • Max
  • MRF-2
  • POU2F1
  • POU2F1a

Genomic Locations for DENND5A Gene

Genomic Locations for DENND5A Gene
chr11:9,138,825-9,265,350
(GRCh38/hg38)
Size:
126,526 bases
Orientation:
Minus strand
chr11:9,160,372-9,286,937
(GRCh37/hg19)
Size:
126,566 bases
Orientation:
Minus strand

Genomic View for DENND5A Gene

Genes around DENND5A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DENND5A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DENND5A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DENND5A Gene

Proteins for DENND5A Gene

  • Protein details for DENND5A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6IQ26-DEN5A_HUMAN
    Recommended name:
    DENN domain-containing protein 5A
    Protein Accession:
    Q6IQ26
    Secondary Accessions:
    • B4DJ15
    • E9PS91
    • Q96GN3
    • Q9H6U7
    • Q9UFV0
    • Q9UPR1

    Protein attributes for DENND5A Gene

    Size:
    1287 amino acids
    Molecular mass:
    147096 Da
    Quaternary structure:
    • Interacts with RAB6A bound to GTP.
    SequenceCaution:
    • Sequence=BAA83043.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15155.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for DENND5A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DENND5A Gene

Post-translational modifications for DENND5A Gene

  • Glycosylation at Thr479 and Ser482
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for DENND5A Gene

Domains & Families for DENND5A Gene

Gene Families for DENND5A Gene

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

Protein Domains for DENND5A Gene

Suggested Antigen Peptide Sequences for DENND5A Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ43455 fis, clone OCBBF2035110, highly similar to Rab6-interacting protein 1 (B3KWN5_HUMAN)
  • cDNA FLJ58453, highly similar to Rab6-interacting protein 1 (B4DFB6_HUMAN)
  • Rab6-interacting protein 1 (DEN5A_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6IQ26

UniProtKB/Swiss-Prot:

DEN5A_HUMAN :
  • Belongs to the RAB6IP1 family.
Family:
  • Belongs to the RAB6IP1 family.
genes like me logo Genes that share domains with DENND5A: view

Function for DENND5A Gene

Molecular function for DENND5A Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity).

Phenotypes From GWAS Catalog for DENND5A Gene

Gene Ontology (GO) - Molecular Function for DENND5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005515 protein binding IEA --
GO:0017112 Rab guanyl-nucleotide exchange factor activity IDA 20937701
GO:0017137 Rab GTPase binding IEA --
genes like me logo Genes that share ontologies with DENND5A: view
genes like me logo Genes that share phenotypes with DENND5A: view

Human Phenotype Ontology for DENND5A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for DENND5A

CRISPR Products

miRNA for DENND5A Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DENND5A

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for DENND5A Gene

Localization for DENND5A Gene

Subcellular locations from UniProtKB/Swiss-Prot for DENND5A Gene

Golgi apparatus membrane.

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 DENND5A gene
Compartment Confidence
golgi apparatus 5
cytosol 4
nucleus 2
endosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DENND5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005794 Golgi apparatus IEA --
GO:0005802 trans-Golgi network IDA 19619496
GO:0005829 cytosol TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with DENND5A: view

Pathways & Interactions for DENND5A Gene

genes like me logo Genes that share pathways with DENND5A: view

Pathways by source for DENND5A Gene

Gene Ontology (GO) - Biological Process for DENND5A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010977 negative regulation of neuron projection development ISS --
GO:0042147 retrograde transport, endosome to Golgi IMP 19619496
genes like me logo Genes that share ontologies with DENND5A: view

No data available for SIGNOR curated interactions for DENND5A Gene

Drugs & Compounds for DENND5A Gene

(1) Drugs for DENND5A Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine triphosphate Experimental Pharma 0
genes like me logo Genes that share compounds with DENND5A: view

Transcripts for DENND5A Gene

mRNA/cDNA for DENND5A Gene

4 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
16 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DENND5A

Alternative Splicing Database (ASD) splice patterns (SP) for DENND5A Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18a · 18b ^
SP1: - - -
SP2: - - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8: -
SP9: - - - - - -
SP10: -

ExUns: 19 ^ 20 ^ 21a · 21b ^ 22 ^ 23a · 23b ^ 24 ^ 25 ^ 26 ^ 27a · 27b · 27c · 27d · 27e
SP1: - -
SP2: - - - - - - -
SP3: - -
SP4: - - - - -
SP5: -
SP6:
SP7:
SP8:
SP9:
SP10:

Relevant External Links for DENND5A Gene

GeneLoc Exon Structure for
DENND5A

Expression for DENND5A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DENND5A Gene

Protein differential expression in normal tissues from HIPED for DENND5A Gene

This gene is overexpressed in Islet of Langerhans (18.9), Ovary (17.1), Platelet (13.2), and Adrenal (9.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for DENND5A Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DENND5A

SOURCE GeneReport for Unigene cluster for DENND5A Gene:

Hs.501857

Evidence on tissue expression from TISSUES for DENND5A Gene

  • Nervous system(4.9)
  • Skin(4.4)
genes like me logo Genes that share expression patterns with DENND5A: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for DENND5A Gene

Orthologs for DENND5A Gene

This gene was present in the common ancestor of animals.

Orthologs for DENND5A Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia DENND5A 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia DENND5A 30 31
  • 94.25 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia DENND5A 31
  • 94 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia DENND5A 31
  • 93 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia DENND5A 30 31
  • 92.96 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Dennd5a 30 17 31
  • 90.99 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Dennd5a 30
  • 90.7 (n)
Chicken
(Gallus gallus)
Aves DENND5A 30 31
  • 80.55 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 91 (a)
OneToMany
-- 31
  • 90 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia dennd5a 30
  • 77.02 (n)
Zebrafish
(Danio rerio)
Actinopterygii dennd5a 30 31
  • 75.24 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG7852 31
  • 39 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea C52E12.4 30
  • 48.05 (n)
lst-6 31
  • 33 (a)
OneToMany
Species where no ortholog for DENND5A was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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 DENND5A Gene

ENSEMBL:
Gene Tree for DENND5A (if available)
TreeFam:
Gene Tree for DENND5A (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DENND5A: view image

Paralogs for DENND5A Gene

Paralogs for DENND5A Gene

(2) SIMAP similar genes for DENND5A Gene using alignment to 10 proteins:

  • DEN5A_HUMAN
  • B3KWN5_HUMAN
  • B4DFB6_HUMAN
  • E9PIS3_HUMAN
  • H0YCW5_HUMAN
  • H0YDE6_HUMAN
  • H0YDS8_HUMAN
  • H0YDV6_HUMAN
  • H0YE63_HUMAN
  • H0YEA8_HUMAN
genes like me logo Genes that share paralogs with DENND5A: view

Variants for DENND5A Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DENND5A Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
715632 Benign: not provided 9,264,989(-) C/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
741225 Benign/Likely Benign: not provided 9,142,762(-) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
780949 Benign: not provided 9,179,071(-) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
806617 Uncertain Significance: not provided 9,160,840(-) A/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
806618 Likely Benign: not provided 9,178,373(-) G/A INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for DENND5A Gene

Structural Variations from Database of Genomic Variants (DGV) for DENND5A Gene

Variant ID Type Subtype PubMed ID
esv33264 CNV loss 17666407
esv3625327 CNV loss 21293372
nsv1055078 CNV gain 25217958
nsv1144533 CNV deletion 24896259
nsv499766 OTHER inversion 21111241
nsv515891 CNV gain 19592680
nsv526778 CNV loss 19592680
nsv7215 OTHER inversion 18451855

Variation tolerance for DENND5A Gene

Residual Variation Intolerance Score: 1.31% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.28; 90.62% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DENND5A Gene

Human Gene Mutation Database (HGMD)
DENND5A
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DENND5A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DENND5A Gene

Disorders for DENND5A Gene

MalaCards: The human disease database

(4) MalaCards diseases for DENND5A Gene - From: OMIM, ClinVar, GTR, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 49
  • eiee49
encephalopathy
  • brain diseases
early infantile epileptic encephalopathy
  • early infantile epileptic encephalopathy with burst-suppression
autosomal recessive non-syndromic intellectual disability
  • autosomal recessive mental retardation
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

DEN5A_HUMAN
  • Epileptic encephalopathy, early infantile, 49 (EIEE49) [MIM:617281]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE49 is a severe autosomal recessive form characterized by onset of seizures in the neonatal period, global developmental delay, intellectual disability, and additionally cerebral calcifications and coarse facial features. {ECO:0000269 PubMed:27431290, ECO:0000269 PubMed:27866705}. Note=The disease is caused by mutations affecting the gene represented in this entry.
genes like me logo Genes that share disorders with DENND5A: view

No data available for Genatlas for DENND5A Gene

Publications for DENND5A Gene

  1. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. (PMID: 20937701) Yoshimura S … Barr FA (The Journal of cell biology 2010) 2 3 4
  2. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10470851) Kikuno R … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1999) 2 3 4
  3. Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A. (PMID: 27866705) Han C … McPherson PS (American journal of human genetics 2016) 3 4
  4. The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. (PMID: 19619496) Wassmer T … Cullen PJ (Developmental cell 2009) 3 23
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for DENND5A Gene

  • Signalway Proteins for DENND5A

Sources for DENND5A Gene