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    FRMD4A FERM domain containing 4A [ Homo sapiens (human) ]

    Gene ID: 55691, updated on 28-Oct-2024

    Summary

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    Official Symbol
    FRMD4Aprovided by HGNC
    Official Full Name
    FERM domain containing 4Aprovided by HGNC
    Primary source
    HGNC:HGNC:25491
    See related
    Ensembl:ENSG00000151474 MIM:616305; AllianceGenome:HGNC:25491
    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
    FRMD4; CCAFCA; bA295P9.4
    Summary
    This gene encodes a FERM domain-containing protein that regulates epithelial cell polarity. It connects ADP ribosylation factor 6 (ARF6) with the Par protein complex, which regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms in this gene are associated with Alzheimer's disease, and also with nicotine dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
    Expression
    Ubiquitous expression in fat (RPKM 10.5), skin (RPKM 7.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FRMD4A in Genome Data Viewer
    Location:
    10p13
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (13643706..14330924, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (13656726..14343958, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (13685706..14372923, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376422 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3055 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:13629435-13630030 Neighboring gene ribosomal protein L6 pseudogene 24 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3057 Neighboring gene pre-mRNA processing factor 18 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:13715567-13716091 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2156 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13732519-13733075 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2157 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13749502-13750237 Neighboring gene uncharacterized LOC124902379 Neighboring gene uncharacterized LOC105376426 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13753704-13754570 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:13754571-13755435 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2158 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3061 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13770188-13771042 Neighboring gene Sharpr-MPRA regulatory region 15561 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3062 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3063 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3064 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:13799977-13801176 Neighboring gene RNA, 5S ribosomal pseudogene 301 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_11339 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3066 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13830309-13830899 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:13868526-13868712 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13912798-13913451 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13922897-13923786 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13923787-13924677 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:13924678-13925567 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3067 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:13946263-13946779 Neighboring gene nuclear transport factor 2 pseudogene 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:13984208-13984392 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:13987981-13988481 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:14013273-14014244 Neighboring gene uncharacterized LOC105376425 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3068 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:14073952-14074117 Neighboring gene uncharacterized LOC101928453 Neighboring gene NANOG hESC enhancer GRCh37_chr10:14135940-14136630 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:14140561-14141060 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:14209403-14209904 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:14209905-14210404 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:14217447-14217946 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:14219306-14219467 Neighboring gene Sharpr-MPRA regulatory region 4256 Neighboring gene uncharacterized LOC124902378 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2159 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3069 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:14297701-14297910 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_11398 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:14406081-14406580 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:14414401-14414901 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:14459182-14460086 Neighboring gene microRNA 4293 Neighboring gene microRNA 1265

    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. Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population. Díaz-Peña R, et al. Arch Bronconeumol, 2022 May. PMID 35312514
    2. FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis. Goldie SJ, et al. Cancer Res, 2012 Jul 1. PMID 22564525, Free PMC Article
    3. Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy. Markunas CA, et al. Environ Health Perspect, 2014 Oct. PMID 24906187, Free PMC Article
    4. Transcriptomics and mechanistic elucidation of Alzheimer's disease risk genes in the brain and in vitro models. Martiskainen H, et al. Neurobiol Aging, 2015 Feb. PMID 25281018
    5. A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A. Fine D, et al. Eur J Hum Genet, 2015 Dec. PMID 25388005, Free PMC Article

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population.", trans "Polimorfismos en el gen FRMD4A se asocian a riesgo de enfermedad pulmonar obstructiva cronica en poblacion latinoamericana.
      Title: Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population.
    2. FRMD4A RNAi or inhibition of cytohesins strongly upregulated secretion of endogenous tau. These results suggest that FRMD4A, a genetic risk factor for late-onset Alzheimer's disease, regulates tau secretion by activating cytohesin-Arf6 signaling.
      Title: FRMD4A-cytohesin signaling modulates the cellular release of tau.
    3. Findings suggest that FRMD4A expression correlates with the development of tongue squamous cell carcinoma.
      Title: FRMD4A: A potential therapeutic target for the treatment of tongue squamous cell carcinoma.
    4. novel microcephaly, intellectual disability and dysmorphism syndrome is associated with a mutation in FRMD4A.
      Title: A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.
    5. data suggest that FRMD4A could be a relevant candidate gene for AD risk.
      Title: Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.
    6. findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified
      Title: FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis.
    7. A single nucleotide polymorphism in the FERM domain containing 4A protein is associated with nicotine dependence.
      Title: Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
    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
    A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.
    EBI GWAS Catalog
    Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
    EBI GWAS Catalog
    Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    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

    • FLJ10210, KIAA1294

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein-macromolecule adaptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in establishment of epithelial cell polarity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of protein secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein secretion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in adherens junction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in bicellular tight junction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    FERM domain-containing protein 4A
    Names
    FERM domain containing 4

    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_047164.1 RefSeqGene

      Range
      4944..692162
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001318336.2 → NP_001305265.1  FERM domain-containing protein 4A isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is longer than isoform a.
      Source sequence(s)
      AC044781, AK001072, AK289693, AL157392, BC151244, BU073361
      UniProtKB/Swiss-Prot
      Q9P2Q2
      UniProtKB/TrEMBL
      Q9NW91
      Conserved Domains (5) summary
      smart00295
      Location:37 → 237
      B41; Band 4.1 homologues
      cd13191
      Location:233 → 343
      FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)
      pfam00373
      Location:123 → 237
      FERM_M; FERM central domain
      pfam09379
      Location:40 → 101
      FERM_N; FERM N-terminal domain
      pfam11819
      Location:400 → 507
      DUF3338; Domain of unknown function (DUF3338)

    2. NM_001318337.2 → NP_001305266.1  FERM domain-containing protein 4A isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is longer than isoform a.
      Source sequence(s)
      AK094045, AK289693, AL157392, BU073361
      UniProtKB/Swiss-Prot
      Q9P2Q2
      Conserved Domains (5) summary
      smart00295
      Location:54 → 254
      B41; Band 4.1 homologues
      cd13191
      Location:250 → 360
      FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)
      pfam00373
      Location:140 → 254
      FERM_M; FERM central domain
      pfam09379
      Location:57 → 118
      FERM_N; FERM N-terminal domain
      pfam11819
      Location:417 → 524
      DUF3338; Domain of unknown function (DUF3338)

    3. NM_001318338.2 → NP_001305267.1  FERM domain-containing protein 4A isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks several 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.
      Source sequence(s)
      AK289693, AL157392, BP278325, BU073361
      UniProtKB/Swiss-Prot
      Q9P2Q2
      Conserved Domains (2) summary
      pfam11819
      Location:47 → 181
      DUF3338; Domain of unknown function (DUF3338)
      cl17171
      Location:1 → 18
      PH-like; Pleckstrin homology-like domain

    4. NM_018027.5 → NP_060497.3  FERM domain-containing protein 4A isoform a

      See identical proteins and their annotated locations for NP_060497.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform a.
      Source sequence(s)
      AC069025, AK289693, AL157392, BC151244, BU073361
      Consensus CDS
      CCDS7101.1
      UniProtKB/Swiss-Prot
      A7E2Y3, Q5T377, Q9P2Q2
      Related
      ENSP00000350032.2, ENST00000357447.7
      Conserved Domains (4) summary
      smart00295
      Location:21 → 221
      B41; Band 4.1 homologues
      cd13191
      Location:217 → 327
      FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)
      cd17200
      Location:18 → 106
      FERM_F1_FRMD4B; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4B (FRMD4B)
      pfam11819
      Location:356 → 490
      DUF3338; Domain of unknown function (DUF3338)

    RNA

    1. NR_134578.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) shares the first two exons with variant 1 but lacks the remaining exons, and instead contains alternate 3' exon structure. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AC069025, AL157896, BC018891, BC151244

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      13643706..14330924 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      13656726..14343958 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9P2Q2.3 GenPept UniProtKB/Swiss-Prot:Q9P2Q2

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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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