Property Summary

NCBI Gene PubMed Count 82
PubMed Score 273.20
PubTator Score 150.76

Knowledge Summary


No data available


  Disease (6)

Disease Target Count Z-score Confidence
Emery-Dreifuss muscular dystrophy 24 0.0 4.0
Disease Target Count Z-score Confidence
Myopathy 128 3.782 1.9
Heart disease 279 3.341 1.7


  Differential Expression (34)

Disease log2 FC p
malignant mesothelioma 5.100 3.0e-09
astrocytic glioma 2.400 1.1e-03
ependymoma 3.000 2.3e-03
oligodendroglioma 2.700 4.5e-04
psoriasis -1.700 9.8e-05
cystic fibrosis -2.084 2.0e-05
Atopic dermatitis -2.500 2.0e-04
adrenocortical carcinoma -1.399 1.8e-03
chronic kidney disease 1.800 3.6e-02
pancreatic ductal adenocarcinoma liver m... -1.044 2.5e-02
non-small cell lung cancer -3.813 2.2e-32
intraductal papillary-mucinous adenoma (... -2.600 3.5e-04
intraductal papillary-mucinous carcinoma... -3.400 1.9e-04
intraductal papillary-mucinous neoplasm ... -3.500 5.4e-04
colon cancer -4.400 1.3e-04
lung cancer -4.400 5.9e-06
active Crohn's disease -2.051 9.6e-03
active ulcerative colitis -2.376 3.3e-02
breast carcinoma -2.400 8.6e-04
fibroadenoma -3.400 1.8e-03
Breast cancer -3.900 2.7e-02
lung adenocarcinoma -3.100 8.3e-21
pediatric high grade glioma 1.300 4.1e-02
sonic hedgehog group medulloblastoma 1.400 4.0e-02
non primary Sjogren syndrome sicca 1.500 1.1e-02
subependymal giant cell astrocytoma -1.836 3.3e-02
invasive ductal carcinoma -4.900 2.0e-04
COPD -1.200 3.1e-03
lung carcinoma -3.000 1.5e-26
ductal carcinoma in situ -3.700 3.3e-04
ovarian cancer -3.800 4.7e-11
Down syndrome 1.100 2.1e-02
dermatomyositis -1.900 2.0e-03
head and neck cancer -1.600 3.8e-02

Gene RIF (57)

26551678 results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.
26146054 FHL1 shRNA could significantly accelerate tumor cell growth via inhibiting the expression of FHL1
26017856 Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth and Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level.
25724586 In healthy individuals, FHL1A is the predominant splice variant and is mainly found in skeletal and cardiac muscle. In two individuals with an Emery-Dreifuss plus phenotype with pulmonary artery hypoplasia and facial dysmorphology, there was demonstrated loss of isoform A and B, and an almost 200-fold overexpression of isoform C.
25695429 FRG1 mice overexpressing FHL1 showed an improvement in the dystrophic phenotype
25305316 FHL-1 is the predominant complement regulator in Bruch's membrane having direct implications for age-related macular degeneration.
25272045 Our results suggest that miR-410 may function as an oncomiR and are consistent with its key function in regulating FHL1 in certain digestive system cancers.
24952875 The study has revealed that FHL1C overexpression induces Jurkat cell apoptosis.
24634512 This is the first study to show that FHL1 mutations identified in several clinically distinct myopathies lead to similar protein aggregation and impair myotube formation.
24516350 These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction
24114807 Data indicate that four-and-a-half LIM domain 1 gene FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.
23975679 Data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations.
23965743 This study demonistrated that the expand the morphologic features of reducing body myopathy , clearly demonstrate the localization of FHL1 in skeletal muscles.
23456229 mutation of FHL1 confers a complex phenotype through both gain- and loss-of-function mechanisms
23169582 performed a clinical, muscle MRI, and histopathological characterization and immunoblot and genetic analysis of the FHL1 protein in a family with 4 individuals affected by reducing body myopathy. Identified a novel missense mutation in FHL1
23123766 FHL1 downregulation is associated with oral squamous cell carcinoma.
22923418 C224W mutation of FHLi protein had slightly elevated pulmonary artery pressure
22778266 A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics.
22689052 FHL1 is a methylation-silenced tumor-suppressor gene on chromosome X in gastrointestinal cancers, and that its silencing contributes to the formation of an epigenetic field for cancerization.
22541254 A mother, daughter, and son suffering from FHL1 myopathy have a mutation in the second LIM domain of fhl1 with musculoskeletal involvement.
22523091 FHL1 is a novel disease gene for hypertrophic cardiomyopathy.
22219185 FHL1-3 inhibit HIF-1 transcriptional activity and HIF-1alpha transactivation domain function by oxygen-independent mechanisms.
22143536 The decrease in or loss of FHL1 expression may be related to the incidence, progression, invasiveness, and metastatic potential of gastric cancer.
22094483 FHL1 dystrophies are associated with myofibrillar myopathies pathology; mutations in the LIM2 domain are associated with reducing bodies composed of distinct tubulofilaments.
22094188 FHL-1 may regulate estrogen receptor signaling function through regulation of AKT activation besides the physical and functional interaction with Estrogen receptor alpha.
22053194 In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed.
21702045 reduced expression of FHL1 may play an important role in the development and progression of lung cancer.
21629301 We report on three British families with a heterogeneous myopathy clinical presentation segregating a single FHL1 gene mutation and haplotype, suggesting that this represents a founder mutation.
21310615 This review will profile each of the FHL1, with a comprehensive analysis of mutations, a comparison of the clinical and histopathological features and will present several hypotheses for the possible disease mechanism(s)--{REVIEW}
21219870 These results indicate that USP15 is involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of SLIM1.
21126853 FHL1 protein expression is downregulated in thoracic aortic dissection.
20969868 FHL1B/PP2A(Cbeta) interaction may illustrate a novel cell-cycle regulatory pathway.
20633900 A novel missense mutation in the LIM2 domain of FHL1 co-segregated with X-linked scapuloperoneal myopathy in the family
20596604 Expression levels of FHL1 mRNA increased in all cell lines tested, as shown by RT-PCR. The methylation index of FHL1 in our samples was significantly higher in 70 BC specimens than in 10 normal bladder epithelium specimens.
20571991 This study reported a novel LIM2 domain mutation in FHL1 in a family with Reducing body myopathy with cytoplasmic bodies and spinal rigidity.
20186852 Our finding expands the phenotypic spectrum of the recently identified FHL1-associated myopathies and widens the differential diagnosis of Emery-Dreifuss-like syndromes.
19850343 The pH-regulated antigen 1 (Pra1) protein was identified as a novel Factor H and FHL-1 binding protein.
19716112 FHL1 should be considered as a gene associated with the X-linked Emery-Dreifuss muscular dystrophy phenotype, as well as with hypertrophic cardiomyopathy.
19687455 As a consequence of C terminal FHL1 gene mutations, the X-linked myopathy characterized by postural muscle atrophy (XMPMA) phenotype and morphotype with cytoplasmic bodies are found.
19401155 The results presented here suggested the cooperative transcriptional regulation of estrogen signaling by FHL1 and RIP140.
19181672 The mutations detected were exclusive to the second LIM domain of FHL1 and were found in both sporadic as well as familial cases of reducing body myopathy.
19171836 Four novel mutations are identified in FHL1: heterozygous missense mutations in patients 1 and 2 (fatal infantile form), in-frame deletion in patient 3, and hemizygous mutation in patient 4. All mutations are located in the second LIM domain of FHL1.
19139564 Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.
19075112 FHL1 appears to modulate muscle mass and strength enhancement.
18758158 Hoxd13 and Fhl1 were expressed in the interdigital tissues of E12.5 rat embryo. Luciferase assay and EMSA identified a novel promoter region of Fhl1 that directly interacts with Hoxd13
18725486 upregulated in various forms of PH, including idiopathic pulmonary arterial hypertension
18465173 Fhl1 gene was underexpressed in clinical gastric cancer.
18281375 Results support a role of FHL1 as a key molecular component in the I(Kur) complex in human atrium, where it likely regulates functional expression of KCNA5.
18274675 a novel laser microdissection/proteomics approach has helped identify both inherited and de novo mutations in FHL1, thereby defining a new X-linked protein aggregation disorder of muscle.
18244901 The results shows that HOXD13 gene mutation was not involved in outbreak in idiopathic congenital talipes equinovarus, but changes of HOXD13 and FHL1 gene expression related to the development of talipes equinovarus malformation.
18179901 In a large Italian-American pedigree with dominant Scapuloperoneal syndrome all of the affected individuals have a missense change (c.365G-->C) in the FHL1 gene encoding FHL1.
18179888 Study characterized a new disorder, X-linked myopathy with postural muscle atrophy (XMPMA), and identified FHL1 as the causative gene.
18073142 These results characterize TLX1 as a dual function regulator whose activity in respect to FHL1 is critically dependent upon its cellular concentration, as well as cell type and promoter context.
17589823 Fasting insulin and insulin sensitivity index responses to exercise training were associated with DNA sequence variation in FHL1 in white men.
17589823 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
16407297 FHL1 is a novel regulator of myosin-binding protein C activity that may have a role in sarcomere assembly
12917103 SLIM1 may play an important role during the early stages of skeletal muscle differentiation, specifically in alpha5beta1-integrin-mediated signaling pathways

AA Sequence


Text Mined References (83)

PMID Year Title
27234031 2016 Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.
26551678 2015 Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies.
26146054 2015 [FHL1 knockdown mediated by lentiviral shRNA promotes the growth of HeLa and HepG2 cells].
26017856 2015 FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest.
25724586 2015 A novel single nucleotide splice site mutation in FHL1 confirms an Emery-Dreifuss plus phenotype with pulmonary artery hypoplasia and facial dysmorphology.
25695429 2015 FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1).
25305316 2014 Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration.
25272045 2014 MiR-410 is overexpressed in liver and colorectal tumors and enhances tumor cell growth by silencing FHL1 via a direct/indirect mechanism.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
24952875 2014 FHL1C induces apoptosis in Notch1-dependent T-ALL cells through an interaction with RBP-J.
24634512 2014 FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation.
24516350 2014 Up-regulated FHL1 expression maybe involved in the prognosis of Hirschsprung's disease.
24114807 2013 Isolated X-linked hypertrophic cardiomyopathy caused by a novel mutation of the four-and-a-half LIM domain 1 gene.
23975679 2014 Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice.
23965743 2013 Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders.
23456229 2013 Dysregulation of FHL1 spliceforms due to an indel mutation produces an Emery-Dreifuss muscular dystrophy plus phenotype.
23169582 2013 Novel FHL1 mutation in a family with reducing body myopathy.
23123766 2013 High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer.
22923418 2012 Spongious hypertrophic cardiomyopathy in patients with mutations in the four-and-a-half LIM domain 1 gene.
22778266 2012 A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics.
22689052 2013 FHL1 on chromosome X is a single-hit gastrointestinal tumor-suppressor gene and contributes to the formation of an epigenetic field defect.
22541254 2012 Selective muscle involvement in a family affected by a second LIM domain mutation of fhl1: an imaging study using computed tomography.
22523091 2012 Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy.
22219185 2012 Four-and-a-half LIM domain proteins inhibit transactivation by hypoxia-inducible factor 1.
22143536 2012 Expression of FHL1 in gastric cancer tissue and its correlation with the invasion and metastasis of gastric cancer.
22094483 2011 Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy.
22094188 2012 Four-and-a-half-LIM protein 1 down-regulates estrogen receptor ? activity through repression of AKT phosphorylation in human breast cancer cell.
22053194 2011 Four and a half LIM protein 1C (FHL1C): a binding partner for voltage-gated potassium channel K(v1.5).
21702045 2012 Downregulation and growth inhibitory role of FHL1 in lung cancer.
21629301 2011 Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene.
21423176 2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for ?-Pix in negative regulation of focal adhesion maturation.
21310615 2011 Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features.
21269460 2011 Initial characterization of the human central proteome.
21219870 2011 Transgenic overexpression of USP15 in the heart induces cardiac remodeling in mice.
21126853 2011 Downregulation of FHL1 expression in thoracic aortic dissection: implications in aortic wall remodeling and pathogenesis of thoracic aortic dissection.
20969868 2010 LIM domain protein FHL1B interacts with PP2A catalytic ? subunit--a novel cell cycle regulatory pathway.
20633900 2010 A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations.
20596604 2010 CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer.
20571991 2010 Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1.
20186852 2010 Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.
19850343 2009 Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein.
19716112 2009 Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.
19687455 2009 Consequences of mutations within the C terminus of the FHL1 gene.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19401155 2009 Four and a half LIM domains 1 (FHL1) and receptor interacting protein of 140kDa (RIP140) interact and cooperate in estrogen signaling.
19181672 2009 Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.
19171836 2009 Novel FHL1 mutations in fatal and benign reducing body myopathy.
19139564 2009 Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.
19075112 2008 Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy.
18758158 2008 HOXD13 may play a role in idiopathic congenital clubfoot by regulating the expression of FHL1.
18725486 2008 Fhl-1, a new key protein in pulmonary hypertension.
18482256 2009 Protein microarray analysis identifies human cellular prion protein interactors.
18465173 2008 Clinical significance of loss of Fhl1 expression in human gastric cancer.
18281375 2008 Four and a half LIM protein 1: a partner for KCNA5 in human atrium.
18274675 2008 Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.
18244901 2008 [Research of HOXD13 and FHL1 in idiopathic congenital talipes equinovarus].
18179901 2008 X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1.
18179888 2008 An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.
18073142 2008 Transcriptional regulation of FHL1 by TLX1/HOX11 is dosage, cell-type and promoter context-dependent.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17589823 2007 Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise.
16407297 2006 Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin filament formation and sarcomere assembly.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15772651 2005 The DNA sequence of the human X chromosome.
15710417 2005 The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2.
15610731 2004 The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14999091 2004 RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12917103 2003 Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces alpha 5 beta 1-integrin-dependent myocyte elongation.
12665801 2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12432079 2002 Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2.
11400158 2001 Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1).
10524257 1999 Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1.
10480922 1999 Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.
10352231 1999 Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1.
10049693 1999 The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle.
9929984 1999 Chromosomal mapping of two RBP-J-related genes: Kyo-T and RBP-L.
9714789 1998 Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1).
8753811 1996 Slim defines a novel family of LIM-proteins expressed in skeletal muscle.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7626119 1995 The developmental regulation of a novel muscle LIM-protein.