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    PLEKHG4 pleckstrin homology and RhoGEF domain containing G4 [ Homo sapiens (human) ]

    Gene ID: 25894, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PLEKHG4provided by HGNC
    Official Full Name
    pleckstrin homology and RhoGEF domain containing G4provided by HGNC
    Primary source
    HGNC:HGNC:24501
    See related
    Ensembl:ENSG00000196155 MIM:609526; AllianceGenome:HGNC:24501
    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
    SCA4; PRTPHN1; ARHGEF44
    Summary
    The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
    Expression
    Broad expression in testis (RPKM 20.1), ovary (RPKM 10.4) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PLEKHG4 in Genome Data Viewer
    Location:
    16q22.1
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (67277580..67289480)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (73071877..73083777)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (67312065..67323383)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67265259-67265760 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67265761-67266260 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7594 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr16:67271286-67272485 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67275498-67276171 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67276172-67276844 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10960 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10961 Neighboring gene formin homology 2 domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10962 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67279559-67280218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7595 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7596 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7597 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7598 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67282619-67283120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67283121-67283620 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67287038-67287220 Neighboring gene solute carrier family 9 member A5 Neighboring gene uncharacterized LOC124903701 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67304537-67304794 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7600 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67313287-67313468 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67318282-67319022 Neighboring gene potassium channel tetramerization domain containing 19 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10963 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7602 Neighboring gene RN7SK pseudogene 118 Neighboring gene leucine rich repeat containing 36

    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. New gene of spinocerebellar ataxia. Teive HA, et al. Brain, 2011 Jul. PMID 21357611
    2. Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Flanigan K, et al. Am J Hum Genet, 1996 Aug. PMID 8755926, Free PMC Article
    3. Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region. Hellenbroich Y, et al. J Neurol, 2003 Jun. PMID 12796826
    4. Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families. Hirano R, et al. Neurogenetics, 2004 Dec. PMID 15455264
    5. An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains. Ishikawa K, et al. Am J Hum Genet, 2005 Aug. PMID 16001362, Free PMC Article

    See all (37) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.
      Title: Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.
    2. Role of the guanine nucleotide exchange factor in Akt2-mediated plasma membrane translocation of GLUT4 in insulin-stimulated skeletal muscle.
      Title: Role of the guanine nucleotide exchange factor in Akt2-mediated plasma membrane translocation of GLUT4 in insulin-stimulated skeletal muscle.
    3. This letter suggested cerebellar ataxia due to a pentanucleotide repeat (TAGAA) expansion on the puratrophin-1 (PLEKHG4) gene on chromosome 16q-22.1.
      Title: New gene of spinocerebellar ataxia.
    4. (TGGAA)(n) repeats in the insertion mutation of PLEKHG4 are related to the pathogenesis of SCA31
      Title: Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan.
    5. Rac1 activation specifically in membrane ruffles by the guanine-nucleotide-exchange factor FLJ00068 is sufficient for insulin induction of glucose uptake into skeletal-muscle cells.
      Title: Activation of the small GTPase Rac1 by a specific guanine-nucleotide-exchange factor suffices to induce glucose uptake into skeletal-muscle cells.
    6. The mutation of c.-16C to T of the PURATROPHIN-1 gene might be rare in SCA patients in China.
      Title: [Study on the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in Chinese patients with spinocerebellar ataxia].
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: [Study on the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in Chinese patients with spinocerebellar ataxia].
    8. Observational study of genotype prevalence. (HuGE Navigator)
      Title: Mutations of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 are not a common genetic cause of cerebellar ataxia in a European population.
    9. Disease locus of 16q-autosomal dominant cerebellar ataxia was definitely confined to a 900-kb genomic region between the SNP04 and the -16C>T substitution in the puratrophin-1 gene in 16q22.1.
      Title: Redefining the disease locus of 16q22.1-linked autosomal dominant cerebellar ataxia.
    10. Spinocerebellar ataxia type 4 (SCA4) is mapped to chromosome 16q22.1 in northern germany.Haplotype analyses refined the gene locus to a 3.69 cM interval between D16S3019 and D16S512.
      Title: Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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

    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

    • DKFZp434I216

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extrinsic component of membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    puratrophin-1
    Names
    PH domain-containing family G member 4
    Purkinje cell atrophy associated protein 1
    pleckstrin homology domain containing, family G (with RhoGef domain) member 4

    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_008439.2 RefSeqGene

      Range
      7023..16971
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001129727.3 → NP_001123199.1  puratrophin-1 isoform 1

      See identical proteins and their annotated locations for NP_001123199.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (1). Variants 2, 3, and 4 encode isoform 1.
      Source sequence(s)
      AK024475, BC054486, DB279205
      Consensus CDS
      CCDS32466.1
      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    2. NM_001129728.2 → NP_001123200.1  puratrophin-1 isoform 1

      See identical proteins and their annotated locations for NP_001123200.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 2. Variants 2, 3, and 4 encode isoform 1.
      Source sequence(s)
      AB197663, AK308298, DB061030
      Consensus CDS
      CCDS32466.1
      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Related
      ENSP00000401118.2, ENST00000427155.6
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    3. NM_001129729.3 → NP_001123201.1  puratrophin-1 isoform 1

      See identical proteins and their annotated locations for NP_001123201.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 2. Variants 2, 3, and 4 encode isoform 1.
      Source sequence(s)
      BC054486, BC063501, DB461411
      Consensus CDS
      CCDS32466.1
      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Related
      ENSP00000368649.3, ENST00000379344.8
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    4. NM_001129731.3 → NP_001123203.1  puratrophin-1 isoform 2

      See identical proteins and their annotated locations for NP_001123203.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and uses an alternate splice site and lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 2. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AB197663, BC054486, CF993821
      Consensus CDS
      CCDS45512.1
      UniProtKB/TrEMBL
      B4E3H4
      Related
      ENSP00000398030.1, ENST00000450733.5
      Conserved Domains (4) summary
      cd13242
      Location:818 → 953
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00169
      Location:843 → 945
      PH; PH domain
      pfam00621
      Location:655 → 826
      RhoGEF; RhoGEF domain
      cl02488
      Location:366 → 517
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      67277580..67289480
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011522987.3 → XP_011521289.1  puratrophin-1 isoform X1

      See identical proteins and their annotated locations for XP_011521289.1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    2. XM_011522988.3 → XP_011521290.1  puratrophin-1 isoform X1

      See identical proteins and their annotated locations for XP_011521290.1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    3. XM_047433897.1 → XP_047289853.1  puratrophin-1 isoform X2

    4. XM_047433899.1 → XP_047289855.1  puratrophin-1 isoform X4

    5. XM_047433895.1 → XP_047289851.1  puratrophin-1 isoform X2

    6. XM_047433893.1 → XP_047289849.1  puratrophin-1 isoform X2

    7. XM_011522986.3 → XP_011521288.1  puratrophin-1 isoform X1

      See identical proteins and their annotated locations for XP_011521288.1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Related
      ENSP00000353646.5, ENST00000360461.9
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    8. XM_047433896.1 → XP_047289852.1  puratrophin-1 isoform X2

    9. XM_011522985.3 → XP_011521287.1  puratrophin-1 isoform X1

      See identical proteins and their annotated locations for XP_011521287.1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4, B4E3H4
      Conserved Domains (3) summary
      cd13242
      Location:899 → 1034
      PH_puratrophin-1; Puratrophin-1 pleckstrin homology (PH) domain
      pfam00621
      Location:736 → 906
      RhoGEF; RhoGEF domain
      cl02488
      Location:447 → 598
      SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

    10. XM_047433894.1 → XP_047289850.1  puratrophin-1 isoform X2

    11. XM_047433898.1 → XP_047289854.1  puratrophin-1 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      73071877..73083777
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380009.1 → XP_054235984.1  puratrophin-1 isoform X1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4

    2. XM_054380007.1 → XP_054235982.1  puratrophin-1 isoform X1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4

    3. XM_054380013.1 → XP_054235988.1  puratrophin-1 isoform X2

    4. XM_054380015.1 → XP_054235990.1  puratrophin-1 isoform X4

    5. XM_054380011.1 → XP_054235986.1  puratrophin-1 isoform X2

    6. XM_054380006.1 → XP_054235981.1  puratrophin-1 isoform X1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4

    7. XM_054380008.1 → XP_054235983.1  puratrophin-1 isoform X1

      UniProtKB/Swiss-Prot
      Q4G0J8, Q4H485, Q56A69, Q58EX7, Q9H7K4, Q9UFW0
      UniProtKB/TrEMBL
      A0A024R6X4

    8. XM_054380010.1 → XP_054235985.1  puratrophin-1 isoform X2

    9. XM_054380012.1 → XP_054235987.1  puratrophin-1 isoform X2

    10. XM_054380014.1 → XP_054235989.1  puratrophin-1 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_015432.3: Suppressed sequence

      Description
      NM_015432.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q58EX7.1 GenPept UniProtKB/Swiss-Prot:Q58EX7

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