This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. This protein is thought to have a role in the assembly of extracellular membranes. Also, this gene is down-regulated during transformation of n... See more...

Aliases for FHL2 Gene

Aliases for FHL2 Gene

  • Four And A Half LIM Domains 2 2 3 5
  • SLIM3 2 3 4
  • DRAL 2 3 4
  • Four And A Half LIM Domains Protein 2 3 4
  • Skeletal Muscle LIM-Protein 3 3 4
  • LIM Domain Protein DRAL 3 4
  • SLIM-3 3 4
  • FHL-2 3 4
  • Down-Regulated In Rhabdomyosarcoma LIM Protein 3
  • Aging-Associated Gene 11 3
  • AAG11 3
  • FHL2 5

External Ids for FHL2 Gene

Previous GeneCards Identifiers for FHL2 Gene

  • GC02M103841
  • GC02M104429
  • GC02M105574
  • GC02M105598
  • GC02M105590
  • GC02M105435
  • GC02M105343
  • GC02M105974
  • GC02M099745

Summaries for FHL2 Gene

Entrez Gene Summary for FHL2 Gene

  • This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. This protein is thought to have a role in the assembly of extracellular membranes. Also, this gene is down-regulated during transformation of normal myoblasts to rhabdomyosarcoma cells and the encoded protein may function as a link between presenilin-2 and an intracellular signaling pathway. Multiple alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2016]

GeneCards Summary for FHL2 Gene

FHL2 (Four And A Half LIM Domains 2) is a Protein Coding gene. Diseases associated with FHL2 include Familial Isolated Dilated Cardiomyopathy and Rhabdomyosarcoma. Among its related pathways are Androgen receptor signaling pathway and RANK Signaling in Osteoclasts. Gene Ontology (GO) annotations related to this gene include identical protein binding and transcription coactivator activity. An important paralog of this gene is FHL5.

UniProtKB/Swiss-Prot Summary for FHL2 Gene

  • May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:28717008).

Gene Wiki entry for FHL2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FHL2 Gene

Genomics for FHL2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FHL2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FHL2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FHL2

Top Transcription factor binding sites by QIAGEN in the FHL2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • CREB
  • deltaCREB

Genomic Locations for FHL2 Gene

Latest Assembly
chr2:105,357,712-105,438,529
(GRCh38/hg38)
Size:
80,818 bases
Orientation:
Minus strand

Previous Assembly
chr2:105,974,169-106,054,986
(GRCh37/hg19 by Entrez Gene)
Size:
80,818 bases
Orientation:
Minus strand

chr2:105,974,169-106,054,970
(GRCh37/hg19 by Ensembl)
Size:
80,802 bases
Orientation:
Minus strand

Genomic View for FHL2 Gene

Genes around FHL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FHL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FHL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FHL2 Gene

Proteins for FHL2 Gene

  • Protein details for FHL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14192-FHL2_HUMAN
    Recommended name:
    Four and a half LIM domains protein 2
    Protein Accession:
    Q14192
    Secondary Accessions:
    • Q13229
    • Q13644
    • Q2I5I4
    • Q5TM15
    • Q9P294

    Protein attributes for FHL2 Gene

    Size:
    279 amino acids
    Molecular mass:
    32193 Da
    Quaternary structure:
    • Interacts with ZNF638 and TTN/titin (PubMed:11813260, PubMed:12432079). Interacts with E4F1 (PubMed:16652157). Interacts with GRB7 (PubMed:18853468). Interacts with SIRT1 and FOXO1 (PubMed:15692560). Interacts with CEFIP (PubMed:28717008). Interacts with calcineurin (By similarity). Interacts with FOXK1 (By similarity).

    Three dimensional structures from OCA and Proteopedia for FHL2 Gene

    Alternative splice isoforms for FHL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FHL2 Gene

Post-translational modifications for FHL2 Gene

  • Ubiquitination at Lys167
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for FHL2 Gene

Domains & Families for FHL2 Gene

Gene Families for FHL2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for FHL2 Gene

InterPro:
Blocks:
  • Zn-binding protein, LIM

Suggested Antigen Peptide Sequences for FHL2 Gene

GenScript: Design optimal peptide antigens:
  • Skeletal muscle LIM-protein 3 (FHL2_HUMAN)
  • Four and a half LIM-domain protein 2 (Q2I5I4_HUMAN)
  • Aging-associated gene 11 (Q2TSB7_HUMAN)
  • cDNA, FLJ94468, Homo sapiens four and a half LIM domains 2 (FHL2), mRNA (Q6I9R8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14192

UniProtKB/Swiss-Prot:

FHL2_HUMAN :
  • The third LIM zinc-binding mediates interaction with E4F1.
Domain:
  • The third LIM zinc-binding mediates interaction with E4F1.
genes like me logo Genes that share domains with FHL2: view

Function for FHL2 Gene

Molecular function for FHL2 Gene

UniProtKB/Swiss-Prot Function:
May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:28717008).
GENATLAS Biochemistry:
four and a half LIM domain protein 2,heart specific form,tissue specific coactivator of the androgen receptor,downregulated in rhabdomyosarcoma

Phenotypes From GWAS Catalog for FHL2 Gene

Gene Ontology (GO) - Molecular Function for FHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003712 transcription coregulator activity IBA 21873635
GO:0003714 transcription corepressor activity ISS --
GO:0005515 protein binding IPI 14550570
GO:0008134 transcription factor binding IPI 15692560
GO:0042802 identical protein binding IPI 10906324
genes like me logo Genes that share ontologies with FHL2: view
genes like me logo Genes that share phenotypes with FHL2: view

Human Phenotype Ontology for FHL2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FHL2 Gene

MGI Knock Outs for FHL2:

miRNA for FHL2 Gene

miRTarBase miRNAs that target FHL2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FHL2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for FHL2 Gene

Localization for FHL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FHL2 Gene

Cytoplasm. Nucleus. Cytoplasm, myofibril, sarcomere, Z line.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FHL2 gene
Compartment Confidence
nucleus 5
cytosol 4
cytoskeleton 3
plasma membrane 2
extracellular 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (4)
  • Focal adhesion sites (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS,IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005925 focal adhesion HDA 21423176
GO:0030018 Z disc IBA 21873635
genes like me logo Genes that share ontologies with FHL2: view

Pathways & Interactions for FHL2 Gene

genes like me logo Genes that share pathways with FHL2: view

SIGNOR curated interactions for FHL2 Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for FHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 15692560
GO:0001649 osteoblast differentiation IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0009725 response to hormone IMP 17975004
GO:0019216 regulation of lipid metabolic process TAS --
genes like me logo Genes that share ontologies with FHL2: view

Drugs & Compounds for FHL2 Gene

(4) Drugs for FHL2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with FHL2: view

Transcripts for FHL2 Gene

mRNA/cDNA for FHL2 Gene

12 REFSEQ mRNAs :
29 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FHL2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for FHL2 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3a · 3b · 3c · 3d ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b · 11c · 11d
SP1: - - -
SP2: - - - -
SP3: - - - - -
SP4: - - - - - -
SP5: - - - - - -
SP6: - - - - -
SP7: - - - - - - - - - - - -
SP8: - - - - - - - - - - - - - -
SP9: - - -
SP10: - - - - - - -
SP11: - -
SP12: - - - - - - - - - - -
SP13: - - - - - - - -

Relevant External Links for FHL2 Gene

GeneLoc Exon Structure for
FHL2

Expression for FHL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FHL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FHL2 Gene

This gene is overexpressed in Heart - Left Ventricle (x18.3) and Ovary (x5.9).

Protein differential expression in normal tissues from HIPED for FHL2 Gene

This gene is overexpressed in Heart (34.2), Fetal heart (11.1), and Amniocyte (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FHL2 Gene



Protein tissue co-expression partners for FHL2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FHL2

SOURCE GeneReport for Unigene cluster for FHL2 Gene:

Hs.443687

mRNA Expression by UniProt/SwissProt for FHL2 Gene:

Q14192-FHL2_HUMAN
Tissue specificity: Expressed in skeletal muscle and heart.

Evidence on tissue expression from TISSUES for FHL2 Gene

  • Heart(4.8)
  • Muscle(4.7)
  • Blood(4.5)
  • Bone marrow(4.4)
  • Kidney(2.4)
  • Intestine(2.4)
  • Stomach(2.3)
  • Skin(2.3)
  • Liver(2.2)
  • Nervous system(2.2)
  • Gall bladder(2.1)
  • Spleen(2.1)
  • Adrenal gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FHL2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
  • heart valve
  • lung
Limb:
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • coagulation system
  • red blood cell
  • spinal cord
genes like me logo Genes that share expression patterns with FHL2: view

Primer products for research

Orthologs for FHL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for FHL2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FHL2 29 30
  • 96.52 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia FHL2 29 30
  • 90.32 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia FHL2 30
  • 90 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Fhl2 29
  • 87.81 (n)
Mouse
(Mus musculus)
Mammalia Fhl2 29 16 30
  • 87.22 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia FHL2 29 30
  • 86.62 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia FHL2 30
  • 70 (a)
OneToOne
Chicken
(Gallus gallus)
Aves FHL2 29 30
  • 81.96 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia FHL2 30
  • 90 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia fhl2 29
  • 79.21 (n)
Zebrafish
(Danio rerio)
Actinopterygii fhl2a 29 30
  • 81.12 (n)
OneToMany
fhl2b 30
  • 81 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Lmpt 29 31
  • 64.47 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005400 29
  • 63.74 (n)
Worm
(Caenorhabditis elegans)
Secernentea lim-9 29 30
  • 57.13 (n)
OneToMany
F25H5.1a 31
  • 55 (a)
F25H5.1b 31
  • 54 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 39 (a)
OneToMany
Species where no ortholog for FHL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for FHL2 Gene

ENSEMBL:
Gene Tree for FHL2 (if available)
TreeFam:
Gene Tree for FHL2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FHL2: view image
Alliance of Genome Resources:
Additional Orthologs for FHL2

Paralogs for FHL2 Gene

Paralogs for FHL2 Gene

(15) SIMAP similar genes for FHL2 Gene using alignment to 11 proteins:

  • FHL2_HUMAN
  • C9J3S8_HUMAN
  • E9PKF4_HUMAN
  • F8WDA8_HUMAN
  • I0CE67_HUMAN
  • J3KNW4_HUMAN
  • Q53QP3_HUMAN
  • Q53T40_HUMAN
  • Q5TM15_HUMAN
  • Q6I9R8_HUMAN
  • U3KQT4_HUMAN
genes like me logo Genes that share paralogs with FHL2: view

Variants for FHL2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FHL2 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1002657 Uncertain Significance: Primary dilated cardiomyopathy 105,367,584(-) C/T
NM_001318895.3(FHL2):c.487G>A (p.Val163Ile)
MISSENSE
1005806 Uncertain Significance: Primary dilated cardiomyopathy 105,386,443(-) C/CT
NM_001318895.3(FHL2):c.73dup (p.Ser25fs)
FRAMESHIFT_VARIANT,FIVE_PRIME_UTR
1007875 Uncertain Significance: Primary dilated cardiomyopathy 105,373,609(-) G/A
NM_001318895.3(FHL2):c.281C>T (p.Ser94Phe)
MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON
1013659 Uncertain Significance: Primary dilated cardiomyopathy 105,361,436(-) T/C
NM_001318895.3(FHL2):c.689-2A>G
SPLICE_ACCEPTOR
1015549 Uncertain Significance: Primary dilated cardiomyopathy 105,367,683(-) G/A
NM_001318895.3(FHL2):c.388C>T (p.His130Tyr)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for FHL2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for FHL2 Gene

Residual Variation Intolerance Score: 35.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.91; 48.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FHL2 Gene

Human Gene Mutation Database (HGMD)
FHL2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FHL2
Leiden Open Variation Database (LOVD)
FHL2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for FHL2 Gene

Disorders for FHL2 Gene

MalaCards: The human disease database

(23) MalaCards diseases for FHL2 Gene - From: ORP, COP, and GCD

Disorder Aliases PubMed IDs
familial isolated dilated cardiomyopathy
  • familial or idiopathic dilated cardiomyopathy
rhabdomyosarcoma
hemophagocytic lymphohistiocytosis, familial, 1
  • fhl1
hemophagocytic lymphohistiocytosis
  • haemophagocytic syndrome
deafness, autosomal recessive 65
  • dfnb65
- elite association - COSMIC cancer census association via MalaCards
Search FHL2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FHL2

genes like me logo Genes that share disorders with FHL2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FHL2 Gene

Publications for FHL2 Gene

  1. Slim defines a novel family of LIM-proteins expressed in skeletal muscle. (PMID: 8753811) Morgan MJ … Madgwick AJ (Biochemical and biophysical research communications 1996) 2 3 4 22
  2. Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy. (PMID: 17416352) Arimura T … Kimura A (Biochemical and biophysical research communications 2007) 3 22 72
  3. Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220. (PMID: 11813260) Ng EK … Fung KP (Journal of cellular biochemistry 2002) 3 4 22
  4. Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein. (PMID: 11001931) Tanahashi H … Tabira T (Human molecular genetics 2000) 3 4 22
  5. Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart. (PMID: 9573400) Chan KK … Lee CY (Gene 1998) 3 4 22

Products for FHL2 Gene

Sources for FHL2 Gene