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    FHL5 four and a half LIM domains 5 [ Homo sapiens (human) ]

    Gene ID: 9457, updated on 9-Dec-2024

    Summary

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    Official Symbol
    FHL5provided by HGNC
    Official Full Name
    four and a half LIM domains 5provided by HGNC
    Primary source
    HGNC:HGNC:17371
    See related
    Ensembl:ENSG00000112214 MIM:605126; AllianceGenome:HGNC:17371
    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
    ACT; FHL-5; dJ393D12.2; 1700027G07Rik
    Summary
    The protein encoded by this gene is coordinately expressed with activator of cAMP-responsive element modulator (CREM). It is associated with CREM and confers a powerful transcriptional activation function. CREM acts as a transcription factor essential for the differentiation of spermatids into mature spermatozoa. There are multiple polyadenylation sites found in this gene. Polymorphisms in this gene may be associated with susceptibility for migraine headaches. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Apr 2016]
    Expression
    Broad expression in testis (RPKM 16.0), fat (RPKM 12.3) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FHL5 in Genome Data Viewer
    Location:
    6q16.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (96562574..96618626)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (97734473..97790488)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (97010450..97066502)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene UFL1 antisense RNA 1 Neighboring gene RNA, 7SL, cytoplasmic 797, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24840 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24841 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:96967525-96968398 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:96968399-96969270 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:96969271-96970142 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:96970143-96971014 Neighboring gene UFM1 specific ligase 1 Neighboring gene RNA, U4 small nuclear 70, pseudogene Neighboring gene ribosomal protein S7 pseudogene 8

    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. FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells. Wong D, et al. Circ Res, 2023 Apr 28. PMID 37017084, Free PMC Article
    2. An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression. Stoffregen EP, et al. Hum Mol Genet, 2011 Jun 15. PMID 21459774, Free PMC Article
    3. A SNP in the ACT gene associated with astrocytosis and rapid cognitive decline in AD. Belbin O, et al. Neurobiol Aging, 2008 Aug. PMID 17368652
    4. Regulation of gene expression in post-meiotic male germ cells: CREM-signalling pathways and male fertility. Hogeveen KN, et al. Hum Fertil (Camb), 2006 Jun. PMID 16825108
    5. Transcription factors governing male fertility. Sassone-Corsi P. Andrologia, 2005 Dec. PMID 16336258

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association of FHL5 and LPA genetic polymorphisms with diabetes mellitus risk: a case-control study.
      Title: Association of FHL5 and LPA genetic polymorphisms with diabetes mellitus risk: a case-control study.
    2. FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.
      Title: FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.
    3. Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population.
      Title: Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population.
    4. Identified CREB activators MAPKAPK3 and FHL5 as mediators of intimal hyperplasia in vein graft samples.
      Title: Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia.
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    6. This protein has been found differentially expressed in thalami from patients with schizophrenia.
      Title: Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia.
    7. Results indicate that SPAG8 acts as a regulator of ACT and plays an important role in CREM-ACT-mediated gene transcription during spermatogenesis.
      Title: Sperm associated antigen 8 (SPAG8), a novel regulator of activator of CREM in testis during spermatogenesis.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent.
    9. No difference was found in the levels of ICER transcripts in thyroid adenomas and surrounding normal tissue (obtained at surgery), independently of the TSH receptor gene status.
      Title: Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas.
    10. Different haplotypes within the ACT gene may contribute to male factor subfertility.
      Title: Sequencing and haplotype analysis of the activator of CREM in the testis (ACT) gene in populations of fertile and infertile males.
    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 study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex.
    EBI GWAS Catalog
    Genome-wide association analysis identifies susceptibility loci for migraine without aura.
    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Microarray analysis indicates HIV-1 Tat-induced downregulation of four and a half LIM domains 5 (FHL5) in primary human brain microvascular endothelial cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ33049, KIAA0776

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Z disc IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    four and a half LIM domains protein 5
    Names
    LIM protein ACT
    activator of cAMP-responsive element modulator (CREM) in testis
    activator of cAMP-responsive element modulator in testis

    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.

    mRNA and Protein(s)

    1. NM_001170807.3 → NP_001164278.1  four and a half LIM domains protein 5

      See identical proteins and their annotated locations for NP_001164278.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 all encode the same protein.
      Source sequence(s)
      AK223539, AL132776, BC021723, BX118342, HY020942
      Consensus CDS
      CCDS5035.1
      UniProtKB/Swiss-Prot
      B2RBD1, E1P526, Q5TD97, Q5TD98, Q8WW21, Q9NQU2
      Related
      ENSP00000442357.1, ENST00000541107.5
      Conserved Domains (5) summary
      cd09343
      Location:37 → 95
      LIM1_FHL; The first LIM domain of Four and a half LIM domains protein (FHL)
      cd09346
      Location:163 → 214
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09347
      Location:222 → 277
      LIM4_FHL; The fourth LIM domain of Four and a half LIM domains protein (FHL)
      cd09428
      Location:102 → 155
      LIM2_FHL5; The second LIM domain of Four and a half LIM domains protein 5 (FHL5)
      cl02475
      Location:5 → 34
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    2. NM_001322466.2 → NP_001309395.1  four and a half LIM domains protein 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 all encode the same protein.
      Source sequence(s)
      AK223539, AL132776, BX118342
      Consensus CDS
      CCDS5035.1
      UniProtKB/Swiss-Prot
      B2RBD1, E1P526, Q5TD97, Q5TD98, Q8WW21, Q9NQU2
      Related
      ENSP00000396390.2, ENST00000450218.6
      Conserved Domains (5) summary
      cd09343
      Location:37 → 95
      LIM1_FHL; The first LIM domain of Four and a half LIM domains protein (FHL)
      cd09346
      Location:163 → 214
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09347
      Location:222 → 277
      LIM4_FHL; The fourth LIM domain of Four and a half LIM domains protein (FHL)
      cd09428
      Location:102 → 155
      LIM2_FHL5; The second LIM domain of Four and a half LIM domains protein 5 (FHL5)
      cl02475
      Location:5 → 34
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    3. NM_001322467.1 → NP_001309396.1  four and a half LIM domains protein 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 all encode the same protein.
      Source sequence(s)
      AK223539, AL132776, BX118342, DA099831
      Consensus CDS
      CCDS5035.1
      UniProtKB/Swiss-Prot
      B2RBD1, E1P526, Q5TD97, Q5TD98, Q8WW21, Q9NQU2
      Conserved Domains (5) summary
      cd09343
      Location:37 → 95
      LIM1_FHL; The first LIM domain of Four and a half LIM domains protein (FHL)
      cd09346
      Location:163 → 214
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09347
      Location:222 → 277
      LIM4_FHL; The fourth LIM domain of Four and a half LIM domains protein (FHL)
      cd09428
      Location:102 → 155
      LIM2_FHL5; The second LIM domain of Four and a half LIM domains protein 5 (FHL5)
      cl02475
      Location:5 → 34
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    4. NM_020482.6 → NP_065228.4  four and a half LIM domains protein 5

      See identical proteins and their annotated locations for NP_065228.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, 3 and 4 all encode the same protein.
      Source sequence(s)
      AK223539, AL132776, BX118342, HY020942
      Consensus CDS
      CCDS5035.1
      UniProtKB/Swiss-Prot
      B2RBD1, E1P526, Q5TD97, Q5TD98, Q8WW21, Q9NQU2
      Related
      ENSP00000326022.2, ENST00000326771.2
      Conserved Domains (5) summary
      cd09343
      Location:37 → 95
      LIM1_FHL; The first LIM domain of Four and a half LIM domains protein (FHL)
      cd09346
      Location:163 → 214
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09347
      Location:222 → 277
      LIM4_FHL; The fourth LIM domain of Four and a half LIM domains protein (FHL)
      cd09428
      Location:102 → 155
      LIM2_FHL5; The second LIM domain of Four and a half LIM domains protein 5 (FHL5)
      cl02475
      Location:5 → 34
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      96562574..96618626
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419567.1 → XP_047275523.1  four and a half LIM domains protein 5 isoform X1

      UniProtKB/Swiss-Prot
      B2RBD1, E1P526, Q5TD97, Q5TD98, Q8WW21, Q9NQU2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      97734473..97790488
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356836.1 → XP_054212811.1  four and a half LIM domains protein 5 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5TD97.1 GenPept UniProtKB/Swiss-Prot:Q5TD97

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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