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

Gene ID: 55691, updated on 5-Mar-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
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Genomic context

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Location:
10p13
Exon count:
30
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (13643706..14330924, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (13656726..14343958, complement)
105.20220307 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
  • 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: A potential therapeutic target for the treatment of tongue squamous cell carcinoma. Zheng X, et al. Int J Mol Med, 2016 Nov. PMID 27666346, Free PMC Article
  3. Differential expression of microRNA in endothelial cells incubated with serum of hypertension patients with blood-stasis syndrome. Wang MM, et al. Chin J Integr Med, 2015 Nov. PMID 25864118
  4. DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring. Küpers LK, et al. Int J Epidemiol, 2015 Aug. PMID 25862628, Free PMC Article
  5. DNA methylation alterations in response to prenatal exposure of maternal cigarette smoking: A persistent epigenetic impact on health from maternal lifestyle? Nielsen CH, et al. Arch Toxicol, 2016 Feb. PMID 25480659

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_2023_10

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

Gene LinkOut

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