DENND5A Gene

HGNC Family	DENN/MADD domain containing (DENND)
Name	DENN/MADD domain containing 5A
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DENND5A (also known as Rab6‐interacting protein 1 or Rab6IP1) is a multifunctional protein that plays key roles in vesicle trafficking and cellular signaling. Structurally, DENND5A contains a DENN domain along with two RUN domains separated by a PLAT domain. The RUN1 domain mediates its binding to Rab6 and underlies its recruitment to Golgi membranes, whereas the RUN2 domain interacts with sorting nexin 1 to help coordinate transport between the Golgi and recycling endosomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In neuronal tissue, DENND5A is highly expressed during development, and loss‐of‐function mutations have been linked to epileptic encephalopathy, likely through mechanisms that include the upregulation of neurotrophin receptors and consequent disruption of neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, studies in the skin context have uncovered a role for DENND5A in pigmentation; truncating variants in DENND5A impair its ability to interact with SNX1, which disrupts the normal transport of SNX1‐associated vesicles from melanosomes, thereby reducing melanin content and linking these variants to an increased susceptibility to melanoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, genomic analyses have identified DENND5A as a candidate gene in intellectual disability, suggesting that its dysfunction may have broader implications in neurodevelopment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In cancer models, knockdown studies in epithelial cells indicate that DENND5A participates in intracellular trafficking and cell cycle progression, with its loss contributing to abnormalities in mitosis and enhanced cell migration, hinting at its role in maintaining normal cell polarity and tissue organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, systematic characterization of DENN domain proteins has revealed that DENND5A functions as a guanine nucleotide exchange factor (GEF) for specific Rab GTPases (in particular, activation of Rab39), thus expanding its role in regulating membrane trafficking cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, DENND5A is central to multiple aspects of vesicle trafficking – by mediating interactions with Rab proteins and other vesicular components – and its disruption is implicated in neurodevelopmental disorders, pigmentation abnormalities, and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Humberto Fernandes, Edward Franklin, Florence Jollivet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0035637"}], "href": "https://doi.org/10.1371/journal.pone.0035637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22558185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22558185"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Humberto Fernandes, Edward Franklin, Amir R Khan "}, {"type": "b", "children": [{"type": "t", "text": "Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr Sect F Struct Biol Cryst Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S174430911100724X"}], "href": "https://doi.org/10.1107/S174430911100724X"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21543860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21543860"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chanshuai Han, Reem Alkhater, Tawfiq Froukh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.10.006"}], "href": "https://doi.org/10.1016/j.ajhg.2016.10.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27866705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27866705"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Muyi Yang, Per Johnsson, Lars Bräutigam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gim.2021.09.003"}], "href": "https://doi.org/10.1016/j.gim.2021.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34906508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34906508"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "S Anazi, S Maddirevula, E Faqeih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2016.113"}], "href": "https://doi.org/10.1038/mp.2016.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27431290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27431290"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yaping Li, Jianing Xu, Huan Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer driver candidate genes AVL9, DENND5A and NUPL1 contribute to MDCK cystogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncoscience (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncoscience.107"}], "href": "https://doi.org/10.18632/oncoscience.107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25621300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25621300"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shin-ichiro Yoshimura, Andreas Gerondopoulos, Andrea Linford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201008051"}], "href": "https://doi.org/10.1083/jcb.201008051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937701"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937701"}]}]}]}
Synonyms	RAB6IP1, EIEE49
Proteins	DEN5A_HUMAN
NCBI Gene ID	23258
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DENND5A has 5,894 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 108 datasets.

Click the + buttons to view associations for DENND5A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DENND5A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DENND5A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DENND5A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of DENND5A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of DENND5A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DENND5A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DENND5A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DENND5A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DENND5A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DENND5A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of DENND5A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DENND5A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DENND5A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DENND5A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of DENND5A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DENND5A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DENND5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DENND5A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DENND5A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing DENND5A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DENND5A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with DENND5A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DENND5A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DENND5A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DENND5A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DENND5A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DENND5A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DENND5A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving DENND5A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DENND5A gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with DENND5A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with DENND5A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DENND5A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DENND5A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DENND5A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DENND5A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DENND5A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DENND5A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DENND5A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing DENND5A from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DENND5A gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.