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    IQSEC2 IQ motif and Sec7 domain ArfGEF 2 [ Homo sapiens (human) ]

    Gene ID: 23096, updated on 10-Dec-2024

    Summary

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    Official Symbol
    IQSEC2provided by HGNC
    Official Full Name
    IQ motif and Sec7 domain ArfGEF 2provided by HGNC
    Primary source
    HGNC:HGNC:29059
    See related
    Ensembl:ENSG00000124313 MIM:300522; AllianceGenome:HGNC:29059
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MRX1; BRAG1; MRX18; MRX78; XLID1; IQ-ArfGEF
    Summary
    This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in brain (RPKM 5.1), adrenal (RPKM 1.4) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IQSEC2 in Genome Data Viewer
    Location:
    Xp11.22
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (53225813..53321350, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (52512100..52607614, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (53262058..53350548, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene lysine demethylase 5C Neighboring gene microRNA 6895 Neighboring gene microRNA 6894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29656 Neighboring gene Sharpr-MPRA regulatory region 5919 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:53285843-53286438 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:53309250-53309449 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:53310370-53311197 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:53317293-53318184 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20857 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20858 Neighboring gene ribosomal protein SA pseudogene 62 Neighboring gene MPV17L2 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Shoubridge C, et al. Nat Genet, 2010 Jun. PMID 20473311, Free PMC Article
    2. A novel splicing mutation in the IQSEC2 gene that modulates the phenotype severity in a family with intellectual disability. Madrigal I, et al. Eur J Hum Genet, 2016 Aug. PMID 26733290, Free PMC Article
    3. IQSEC2 and X-linked syndromal intellectual disability. Alexander-Bloch AF, et al. Psychiatr Genet, 2016 Jun. PMID 27010919, Free PMC Article
    4. The molecular and phenotypic spectrum of IQSEC2-related epilepsy. Zerem A, et al. Epilepsia, 2016 Nov. PMID 27665735
    5. Gonadal mosaicism of a novel IQSEC2 variant causing female limited intellectual disability and epilepsy. Ewans LJ, et al. Eur J Hum Genet, 2017 Jun. PMID 28295038, Free PMC Article

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Molecular modeling of ARF6 dysregulation caused by mutations in IQSEC2.
      Title: Molecular modeling of ARF6 dysregulation caused by mutations in IQSEC2.
    2. Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.
      Title: Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.
    3. Molecular Insights into IQSEC2 Disease.
      Title: Molecular Insights into IQSEC2 Disease.
    4. [Genotypes and phenotypes of IQSEC2 gene variants related epilepsy].
      Title: [Genotypes and phenotypes of IQSEC2 gene variants related epilepsy].
    5. Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder.
      Title: Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder.
    6. IQSEC2-related encephalopathy in males due to missense variants in the pleckstrin homology domain.
      Title: IQSEC2-related encephalopathy in males due to missense variants in the pleckstrin homology domain.
    7. Characterization of spontaneous seizures and EEG abnormalities in a mouse model of the human A350V IQSEC2 mutation and identification of a possible target for precision medicine based therapy.
      Title: Characterization of spontaneous seizures and EEG abnormalities in a mouse model of the human A350V IQSEC2 mutation and identification of a possible target for precision medicine based therapy.
    8. IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?
      Title: IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?
    9. Coexistence of a Homozygous Chromosome 4q35.2 Deletion and Hidden IQSEC2 Pathogenic Variant in a Child with Intellectual Disability.
      Title: Coexistence of a Homozygous Chromosome 4q35.2 Deletion and Hidden IQSEC2 Pathogenic Variant in a Child with Intellectual Disability.
    10. Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy.
      Title: Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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

    Associated conditions

    Description Tests
    Intellectual disability, X-linked 1
    MedGen: C2931498 OMIM: 309530 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0522

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in actin cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in modulation of chemical synaptic transmission IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in modulation of chemical synaptic transmission IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of long-term synaptic depression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of synapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of synaptic transmission, glutamatergic IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of ARF protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in Schaffer collateral - CA1 synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in Schaffer collateral - CA1 synapse IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    IQ motif and SEC7 domain-containing protein 2
    Names
    IQ motif and Sec7 domain 2
    brefeldin A resistant Arf-guanine nucleotide exchange factor 1
    brefeldin A resistant Arf-guanine nucleotide exchange factor 1b
    brefeldin A resistant Arf-guanine nucleotide exchange factor 1c

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_021296.2 RefSeqGene

      Range
      5001..93475
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1194

    mRNA and Protein(s)

    1. NM_001111125.3 → NP_001104595.1  IQ motif and SEC7 domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001104595.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AB011094, AC245102, AL139396
      Consensus CDS
      CCDS48130.1
      UniProtKB/Swiss-Prot
      A0A1W2PQN3, B3KT97, C7SDG1, O60275, Q5JU85, Q5JUX1
      UniProtKB/TrEMBL
      A0A9L9PY69
      Related
      ENSP00000495726.1, ENST00000642864.1
      Conserved Domains (3) summary
      pfam01369
      Location:753 → 941
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:961 → 1093
      IQ_SEC7_PH; PH domain

    2. NM_001243197.2 → NP_001230126.1  IQ motif and SEC7 domain-containing protein 2 isoform 3

      See identical proteins and their annotated locations for NP_001230126.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) shares no exons with variant 1, and differs in the 3' UTR and coding region compared to variant 2. The encoded isoform (3) is significantly shorter and has a distinct C-terminus, compared to isoform 2.
      Source sequence(s)
      BC108674, BX119489
      Consensus CDS
      CCDS87748.1
      UniProtKB/TrEMBL
      A0A1W2PPD3
      Related
      ENSP00000491796.1, ENST00000639161.2

    3. NM_001410736.1 → NP_001397665.1  IQ motif and SEC7 domain-containing protein 2 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC245102, AL139396
      Consensus CDS
      CCDS94612.1
      UniProtKB/TrEMBL
      A0A1W2PR28
      Related
      ENSP00000492403.1, ENST00000640694.1

    4. NM_015075.2 → NP_055890.1  IQ motif and SEC7 domain-containing protein 2 isoform 2

      See identical proteins and their annotated locations for NP_055890.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at a novel ATG and an isoform (2) with distinct N- and C-termini, compared to isoform 1.
      Source sequence(s)
      AB011094, AK095232
      Consensus CDS
      CCDS35298.1
      UniProtKB/Swiss-Prot
      Q5JU85
      Related
      ENSP00000364514.2, ENST00000375365.2
      Conserved Domains (2) summary
      pfam01369
      Location:548 → 736
      Sec7; Sec7 domain
      pfam16453
      Location:756 → 893
      IQ_SEC7_PH; PH domain

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      53225813..53321350 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047441928.1 → XP_047297884.1  IQ motif and SEC7 domain-containing protein 2 isoform X9

    2. XM_006724582.5 → XP_006724645.1  IQ motif and SEC7 domain-containing protein 2 isoform X7

      Conserved Domains (3) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:996 → 1125
      IQ_SEC7_PH; PH domain

    3. XM_047441929.1 → XP_047297885.1  IQ motif and SEC7 domain-containing protein 2 isoform X11

    4. XM_006724583.5 → XP_006724646.1  IQ motif and SEC7 domain-containing protein 2 isoform X8

      Conserved Domains (2) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam16453
      Location:998 → 1125
      IQ_SEC7_PH; PH domain

    5. XM_006724581.5 → XP_006724644.1  IQ motif and SEC7 domain-containing protein 2 isoform X5

      Conserved Domains (3) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:996 → 1125
      IQ_SEC7_PH; PH domain

    6. XM_047441932.1 → XP_047297888.1  IQ motif and SEC7 domain-containing protein 2 isoform X15

    7. XM_006724584.4 → XP_006724647.1  IQ motif and SEC7 domain-containing protein 2 isoform X10

      Conserved Domains (3) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:996 → 1125
      IQ_SEC7_PH; PH domain

    8. XM_006724579.4 → XP_006724642.1  IQ motif and SEC7 domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A0A9L9PY69
      Conserved Domains (3) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:996 → 1125
      IQ_SEC7_PH; PH domain

    9. XM_047441933.1 → XP_047297889.1  IQ motif and SEC7 domain-containing protein 2 isoform X16

    10. XM_011530773.3 → XP_011529075.1  IQ motif and SEC7 domain-containing protein 2 isoform X4

      See identical proteins and their annotated locations for XP_011529075.1

      UniProtKB/TrEMBL
      A0A9L9PY69
      Conserved Domains (3) summary
      pfam01369
      Location:516 → 704
      Sec7; Sec7 domain
      pfam16453
      Location:724 → 861
      IQ_SEC7_PH; PH domain
      cl41729
      Location:1081 → 1188
      KLF1_2_4_N; N-terminal domain of Kruppel-like factor (KLF) 1, KLF2, KLF4, and similar proteins

    11. XM_006724580.4 → XP_006724643.1  IQ motif and SEC7 domain-containing protein 2 isoform X3

      See identical proteins and their annotated locations for XP_006724643.1

      UniProtKB/TrEMBL
      A0A9L9PY69
      Conserved Domains (3) summary
      pfam01369
      Location:548 → 736
      Sec7; Sec7 domain
      pfam16453
      Location:756 → 893
      IQ_SEC7_PH; PH domain
      cl41729
      Location:1113 → 1220
      KLF1_2_4_N; N-terminal domain of Kruppel-like factor (KLF) 1, KLF2, KLF4, and similar proteins

    12. XM_047441931.1 → XP_047297887.1  IQ motif and SEC7 domain-containing protein 2 isoform X14

    13. XM_017029360.2 → XP_016884849.1  IQ motif and SEC7 domain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      A0A9L9PY69
      Conserved Domains (2) summary
      pfam01369
      Location:587 → 775
      Sec7; Sec7 domain
      pfam16453
      Location:798 → 927
      IQ_SEC7_PH; PH domain

    14. XM_011530774.4 → XP_011529076.1  IQ motif and SEC7 domain-containing protein 2 isoform X6

      Conserved Domains (2) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam16453
      Location:998 → 1125
      IQ_SEC7_PH; PH domain

    15. XM_011530777.3 → XP_011529079.1  IQ motif and SEC7 domain-containing protein 2 isoform X13

      Conserved Domains (2) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam16453
      Location:998 → 1125
      IQ_SEC7_PH; PH domain

    16. XM_011530776.3 → XP_011529078.1  IQ motif and SEC7 domain-containing protein 2 isoform X12

      Conserved Domains (3) summary
      pfam01369
      Location:785 → 973
      Sec7; Sec7 domain
      pfam08614
      Location:23 → 64
      ATG16; Autophagy protein 16 (ATG16)
      pfam16453
      Location:996 → 1124
      IQ_SEC7_PH; PH domain

    RNA

    1. XR_938365.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      52512100..52607614 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054326709.1 → XP_054182684.1  IQ motif and SEC7 domain-containing protein 2 isoform X7

    2. XM_054326711.1 → XP_054182686.1  IQ motif and SEC7 domain-containing protein 2 isoform X9

    3. XM_054326713.1 → XP_054182688.1  IQ motif and SEC7 domain-containing protein 2 isoform X11

    4. XM_054326710.1 → XP_054182685.1  IQ motif and SEC7 domain-containing protein 2 isoform X8

    5. XM_054326707.1 → XP_054182682.1  IQ motif and SEC7 domain-containing protein 2 isoform X5

    6. XM_054326717.1 → XP_054182692.1  IQ motif and SEC7 domain-containing protein 2 isoform X15

    7. XM_054326712.1 → XP_054182687.1  IQ motif and SEC7 domain-containing protein 2 isoform X10

    8. XM_054326703.1 → XP_054182678.1  IQ motif and SEC7 domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A0A9L9PY69

    9. XM_054326718.1 → XP_054182693.1  IQ motif and SEC7 domain-containing protein 2 isoform X16

    10. XM_054326706.1 → XP_054182681.1  IQ motif and SEC7 domain-containing protein 2 isoform X4

      UniProtKB/TrEMBL
      A0A9L9PY69

    11. XM_054326705.1 → XP_054182680.1  IQ motif and SEC7 domain-containing protein 2 isoform X3

      UniProtKB/TrEMBL
      A0A9L9PY69

    12. XM_054326716.1 → XP_054182691.1  IQ motif and SEC7 domain-containing protein 2 isoform X14

    13. XM_054326704.1 → XP_054182679.1  IQ motif and SEC7 domain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      A0A9L9PY69

    14. XM_054326708.1 → XP_054182683.1  IQ motif and SEC7 domain-containing protein 2 isoform X6

    15. XM_054326715.1 → XP_054182690.1  IQ motif and SEC7 domain-containing protein 2 isoform X13

    16. XM_054326714.1 → XP_054182689.1  IQ motif and SEC7 domain-containing protein 2 isoform X12

    RNA

    1. XR_008485472.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5JU85.2 GenPept UniProtKB/Swiss-Prot:Q5JU85

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