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

Gene ID: 23096, updated on 11-Apr-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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Location:
Xp11.22
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (53225813..53321350, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (52512100..52607614, complement)
105.20220307 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: 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. [Genotypes and phenotypes of IQSEC2 gene variants related epilepsy]. Wang DH, et al. Zhonghua Er Ke Za Zhi, 2022 Dec 2. PMID 36444437
  2. Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder. Baladron B, et al. Int J Mol Sci, 2022 Aug 22. PMID 36012761, Free PMC Article
  3. IQSEC2-related encephalopathy in males due to missense variants in the pleckstrin homology domain. Shoubridge C, et al. Clin Genet, 2022 Jul. PMID 35347702, Free PMC Article
  4. Coexistence of a Homozygous Chromosome 4q35.2 Deletion and Hidden IQSEC2 Pathogenic Variant in a Child with Intellectual Disability. Karaman Mercan T, et al. Cytogenet Genome Res, 2021. PMID 34229322
  5. IQSEC2 disorder: A new disease entity or a Rett spectrum continuum? Lopergolo D, et al. Clin Genet, 2021 Mar. PMID 33368194

See all (61) 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

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-04-07)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-04-07)

ClinGen Genome Curation PagePubMed

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

  • KIAA0522

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables guanyl-nucleotide exchange factor activity IMP
Inferred from Mutant Phenotype
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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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_2023_10

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

  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

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

  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

  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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