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    DENND1B DENN domain containing 1B [ Homo sapiens (human) ]

    Gene ID: 163486, updated on 28-Oct-2024

    Summary

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    Official Symbol
    DENND1Bprovided by HGNC
    Official Full Name
    DENN domain containing 1Bprovided by HGNC
    Primary source
    HGNC:HGNC:28404
    See related
    Ensembl:ENSG00000213047 MIM:613292; AllianceGenome:HGNC:28404
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FAM31B; C1ORF18; C1orf218
    Summary
    Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]
    Expression
    Ubiquitous expression in colon (RPKM 1.5), thyroid (RPKM 1.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DENND1B in Genome Data Viewer
    Location:
    1q31.3
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (197504748..197782150, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (196766532..197041541, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (197473878..197744610, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904477 Neighboring gene crumbs cell polarity complex component 1 Neighboring gene mitochondrial ribosomal protein S21 pseudogene 3 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:197541395-197542594 Neighboring gene MPRA-validated peak643 silencer Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 32 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1661 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1662 Neighboring gene Sharpr-MPRA regulatory region 12429 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2276 Neighboring gene RPL24 pseudogene 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197757007-197757507 Neighboring gene family with sequence similarity 204 member B, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197769368-197770108 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:197771590-197772329 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:197779872-197780608 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:197782608-197783566 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:197783567-197784524 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:197859970-197860527 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197887073-197887799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197890605-197891127 Neighboring gene chromosome 1 open reading frame 53 Neighboring gene LIM homeobox 9

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Variation at DENND1B and Asthma on the Island of Tristan da Cunha. Duffy DL, et al. Twin Res Hum Genet, 2019 Oct. PMID 31608842
    2. Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children. Fiuza BSD, et al. Mol Immunol, 2017 Oct. PMID 28668455
    3. DENND1B gene variants associate with elevated exhaled nitric oxide in healthy high-risk neonates. Chawes BL, et al. Pediatr Pulmonol, 2015 Feb. PMID 24347560
    4. Variants of DENND1B associated with asthma in children. Sleiman PM, et al. N Engl J Med, 2010 Jan 7. PMID 20032318
    5. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Wu X, et al. Proc Natl Acad Sci U S A, 2011 Nov 15. PMID 22065758, Free PMC Article

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Variation at DENND1B and Asthma on the Island of Tristan da Cunha.
      Title: Variation at DENND1B and Asthma on the Island of Tristan da Cunha.
    2. polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma.
      Title: Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children.
    3. Study reveals a previously unrecognized mechanism by which DENND1B regulates surface TCR dynamics to fine-tune TH2 cell signaling and effector functions. Dennd1b-/- TH2 cells exhibit delayed TCR downmodulation following TCR activation that is associated with enhanced TCR signaling and greater transcriptional activation and secretion of TH2-associated cytokines.
      Title: Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease.
    4. Increased fraction of exhaled nitric oxide in healthy newborns seems strongly influenced by genetics including father's atopy and child's variants in the DENND1B locus at chromosome 1q31.3.
      Title: DENND1B gene variants associate with elevated exhaled nitric oxide in healthy high-risk neonates.
    5. The guanine nucleotide exchange factor activity of connecdenn 1 and 2 are autoinhibited, and this is regulated by Akt activation downstream of insulin stimulation.
      Title: Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors.
    6. Data indicate that folliculin-CT is structurally similar to the DENN domain of DENND1B.
      Title: Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.
    7. analysis of DENND1B-S complexed with its substrate Rab35
      Title: Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Analyses of shared genetic factors between asthma and obesity in children.
    9. We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma.
      Title: Variants of DENND1B associated with asthma in children.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
    EBI GWAS Catalog
    Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Variants of DENND1B associated with asthma in children.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20054, FLJ21179, FLJ33888, MGC27044, MGC103810, DKFZp547O0715

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphatidylinositol phosphate binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in T cell receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in endocytic recycling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in endocytic recycling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in endocytosis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of GTPase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of T-helper 2 cell cytokine production IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in clathrin-coated vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in intracellular membrane-bounded organelle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nuclear speck IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    DENN domain-containing protein 1B
    Names
    DENN/MADD domain containing 1B
    connecdenn 2
    family with sequence similarity 31, member B

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_001195215.2 → NP_001182144.1  DENN domain-containing protein 1B isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
      Source sequence(s)
      AI692985, AK093982, AL139136, BC074735, BK006960, BP220095, DA495773
      Consensus CDS
      CCDS72997.1
      UniProtKB/Swiss-Prot
      B5MD89, D3PFD5, Q5T3B8, Q5T3B9, Q5T3C1, Q5TAI8, Q6B0I8, Q6P3S1, Q8NDT1, Q8TBE6, Q9H774, Q9NXU2
      Related
      ENSP00000479816.1, ENST00000620048.6
      Conserved Domains (3) summary
      smart00801
      Location:323 → 388
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:94 → 291
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:9 → 89
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    2. NM_001195216.2 → NP_001182145.1  DENN domain-containing protein 1B isoform 4

      See identical proteins and their annotated locations for NP_001182145.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR, compared to variant 3. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 3.
      Source sequence(s)
      BC063456, DA495773
      UniProtKB/Swiss-Prot
      Q6P3S1
      Related
      ENST00000468589.5

    3. NM_001300858.2 → NP_001287787.1  DENN domain-containing protein 1B isoform 5

      See identical proteins and their annotated locations for NP_001287787.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains multiple differences at the 5' and 3' ends, compared to variant 3, including initiation of translation at an alternate start codon. The resulting isoform (5) has distinct N- and C-termini and is shorter than isoform 3.
      Source sequence(s)
      AL139136, BC022561, BC063877, DA495773
      Consensus CDS
      CCDS72996.1
      UniProtKB/Swiss-Prot
      Q6P3S1
      Related
      ENSP00000235453.4, ENST00000235453.8
      Conserved Domains (3) summary
      smart00801
      Location:293 → 358
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:84 → 261
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:11 → 79
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    4. NM_144977.5 → NP_659414.2  DENN domain-containing protein 1B isoform 2

      See identical proteins and their annotated locations for NP_659414.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 3. The resulting isoform (2) has a distinct C-terminus and is shorter than isoform 3.
      Source sequence(s)
      AL139136, BC063877, DA495773
      Consensus CDS
      CCDS41452.2
      UniProtKB/Swiss-Prot
      Q6P3S1
      Related
      ENSP00000356366.3, ENST00000367396.7
      Conserved Domains (3) summary
      smart00801
      Location:323 → 388
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:94 → 291
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:9 → 89
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    RNA

    1. NR_125340.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) lacks three alternate internal exons, compared to variant 3. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 3, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AI692985, AK091207, AK093982, AL139136, BC074735, BK006960, DA495773

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      197504748..197782150 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011509248.3 → XP_011507550.1  DENN domain-containing protein 1B isoform X2

      Conserved Domains (3) summary
      smart00801
      Location:336 → 401
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:107 → 304
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:22 → 102
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    2. XM_047447711.1 → XP_047303667.1  DENN domain-containing protein 1B isoform X7

    3. XM_005244931.3 → XP_005244988.1  DENN domain-containing protein 1B isoform X5

      See identical proteins and their annotated locations for XP_005244988.1

      Conserved Domains (3) summary
      smart00801
      Location:303 → 368
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:94 → 271
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:9 → 89
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    4. XM_024453626.2 → XP_024309394.1  DENN domain-containing protein 1B isoform X7

      Conserved Domains (2) summary
      smart00801
      Location:122 → 187
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:1 → 90
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN

    5. XM_011509249.3 → XP_011507551.1  DENN domain-containing protein 1B isoform X4

      See identical proteins and their annotated locations for XP_011507551.1

      Conserved Domains (3) summary
      smart00801
      Location:313 → 378
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:84 → 281
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:11 → 79
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    6. XM_011509247.2 → XP_011507549.1  DENN domain-containing protein 1B isoform X3

      Conserved Domains (3) summary
      smart00801
      Location:351 → 416
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:142 → 319
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:57 → 137
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    7. XM_011509246.3 → XP_011507548.1  DENN domain-containing protein 1B isoform X1

      Conserved Domains (3) summary
      smart00801
      Location:371 → 436
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:142 → 339
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:57 → 137
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    8. XM_047447700.1 → XP_047303656.1  DENN domain-containing protein 1B isoform X6

    9. XM_047447715.1 → XP_047303671.1  DENN domain-containing protein 1B isoform X8

    10. XM_006711194.4 → XP_006711257.1  DENN domain-containing protein 1B isoform X9

      Conserved Domains (1) summary
      smart00801
      Location:17 → 82
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

    11. XM_047447731.1 → XP_047303687.1  DENN domain-containing protein 1B isoform X13

      Related
      ENSP00000294737.7, ENST00000294737.11

    12. XM_047447730.1 → XP_047303686.1  DENN domain-containing protein 1B isoform X12

    13. XM_011509251.4 → XP_011507553.1  DENN domain-containing protein 1B isoform X10

      Conserved Domains (3) summary
      smart00801
      Location:371 → 434
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00799
      Location:142 → 339
      DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
      smart00800
      Location:57 → 137
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

    14. XM_047447726.1 → XP_047303682.1  DENN domain-containing protein 1B isoform X11

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      196766532..197041541 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334715.1 → XP_054190690.1  DENN domain-containing protein 1B isoform X2

    2. XM_054334721.1 → XP_054190696.1  DENN domain-containing protein 1B isoform X7

    3. XM_054334718.1 → XP_054190693.1  DENN domain-containing protein 1B isoform X5

    4. XM_054334716.1 → XP_054190691.1  DENN domain-containing protein 1B isoform X3

    5. XM_054334714.1 → XP_054190689.1  DENN domain-containing protein 1B isoform X1

    6. XM_054334720.1 → XP_054190695.1  DENN domain-containing protein 1B isoform X7

    7. XM_054334717.1 → XP_054190692.1  DENN domain-containing protein 1B isoform X4

    8. XM_054334719.1 → XP_054190694.1  DENN domain-containing protein 1B isoform X6

    9. XM_054334722.1 → XP_054190697.1  DENN domain-containing protein 1B isoform X8

    10. XM_054334723.1 → XP_054190698.1  DENN domain-containing protein 1B isoform X9

    11. XM_054334727.1 → XP_054190702.1  DENN domain-containing protein 1B isoform X13

    12. XM_054334726.1 → XP_054190701.1  DENN domain-containing protein 1B isoform X12

    13. XM_054334724.1 → XP_054190699.1  DENN domain-containing protein 1B isoform X10

    14. XM_054334725.1 → XP_054190700.1  DENN domain-containing protein 1B isoform X11

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001142795.1: Suppressed sequence

      Description
      NM_001142795.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

    2. NM_019049.1: Suppressed sequence

      Description
      NM_019049.1: This RefSeq was suppressed because the CDS was partial.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6P3S1.2 GenPept UniProtKB/Swiss-Prot:Q6P3S1

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    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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