FLG Gene (Protein Coding)

Filaggrin

GC01M152274
GIFtS:
42
The protein encoded by this gene is an intermediate filament-associated protein that aggregates keratin intermediate filaments in mammalian epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of multiple filaggrin units of 324 aa each), which is localized in keratohyalin granules, and is subsequently proteolytically processed into individ... See more...

Aliases for FLG Gene

Aliases for FLG Gene

  • Filaggrin 2 3 4 5
  • Epidermal Filaggrin 3
  • ATOD2 3

External Ids for FLG Gene

Previous GeneCards Identifiers for FLG Gene

  • GC01M150115
  • GC01M148057
  • GC01M149049
  • GC01M149491
  • GC01M149089
  • GC01M150541
  • GC01M123649

Summaries for FLG Gene

Entrez Gene Summary for FLG Gene

  • The protein encoded by this gene is an intermediate filament-associated protein that aggregates keratin intermediate filaments in mammalian epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of multiple filaggrin units of 324 aa each), which is localized in keratohyalin granules, and is subsequently proteolytically processed into individual functional filaggrin molecules. Mutations in this gene are associated with ichthyosis vulgaris.[provided by RefSeq, Dec 2009]

GeneCards Summary for FLG Gene

FLG (Filaggrin) is a Protein Coding gene. Diseases associated with FLG include Ichthyosis Vulgaris and Dermatitis, Atopic, 2. Among its related pathways are Developmental Biology and Keratinization. Gene Ontology (GO) annotations related to this gene include calcium ion binding and structural molecule activity. An important paralog of this gene is HRNR.

UniProtKB/Swiss-Prot Summary for FLG Gene

  • Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.

Additional gene information for FLG Gene

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

Genomics for FLG Gene

GeneHancer (GH) Regulatory Elements for FLG Gene

Promoters and enhancers for FLG Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH01J152325 Promoter 0.3 EPDnew 750.6 0.0 -2 0.1 FLG piR-61354 FLG-AS1
GH01J152188 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas 13.3 +135.8 135767 2.1 CTCF MAX RAD21 POLR2A CBFA2T2 ELF1 ZSCAN21 PKNOX1 RFX1 REST FLG-AS1 HRNR FLG piR-48918 PUDPP2
GH01J151508 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 6.8 +812.1 812138 8.9 SREBF1 MLX FOXA1 RBPJ TCF7L2 USF2 ZNF217 CREB1 MIXL1 NFYC CGN lnc-POGZ-1 lnc-POGZ-2 SETDB1 PIP5K1A ARNT PI4KB UBE2D3P3 MRPL9 GABPB2
GH01J152392 Enhancer 1 Ensembl ENCODE 17.6 -67.8 -67844 1 GATA3 TCF7L2 ZNF217 ZNF362 TEAD4 NFIB BCL6B NCOA3 SP7 ZSCAN21 MRPL9 POGZ FLG HRNR ENSG00000223861 FLG2 PSMB4 HMGN3P1 L13713-016 FLG-AS1
GH01J151822 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 5 +497.6 497635 12 LCORL FOXA1 MLX RBPJ POLR2A HLF MNT MTA3 NFIB ZNF148 RORC AB372574 ZNF687 PIP5K1A SETDB1 LYSMD1 LINGO4 FLG-AS1 THEM4 ENSG00000269621
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FLG on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the FLG gene promoter:
  • AML1a
  • C/EBPalpha
  • CUTL1
  • E47
  • Lmo2
  • Pax-3
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • STAT5A
  • Tal-1

Genomic Locations for FLG Gene

Genomic Locations for FLG Gene
chr1:152,302,163-152,325,257
(GRCh38/hg38)
Size:
23,095 bases
Orientation:
Minus strand
chr1:152,274,651-152,297,679
(GRCh37/hg19)
Size:
23,029 bases
Orientation:
Minus strand

Genomic View for FLG Gene

Genes around FLG on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for FLG Gene

Proteins for FLG Gene

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

    Protein Symbol:
    P20930-FILA_HUMAN
    Recommended name:
    Filaggrin
    Protein Accession:
    P20930
    Secondary Accessions:
    • Q01720
    • Q5T583
    • Q9UC71

    Protein attributes for FLG Gene

    Size:
    4061 amino acids
    Molecular mass:
    435170 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for FLG Gene

neXtProt entry for FLG Gene

Protein Expression for FLG Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FLG Gene

  • Filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 AA, which are not separated by large linker sequences. During terminal differentiation it is dephosphorylated and proteolytically cleaved. The N-terminal of the mature protein is heterogeneous, and is blocked by the formation of pyroglutamate.
  • Undergoes deimination of some arginine residues (citrullination).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FLG Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for FLG Gene

Domains & Families for FLG Gene

Gene Families for FLG Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for FLG Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FLG Gene

GenScript: Design optimal peptide antigens:
  • Filaggrin (FILA_HUMAN)
  • Profilaggrin (Q03837_HUMAN)
  • Profilaggrin (Q03838_HUMAN)
  • Profilaggrin (Q03839_HUMAN)
  • Profilaggrin (Q15206_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P20930

UniProtKB/Swiss-Prot:

FILA_HUMAN :
  • Belongs to the S100-fused protein family.
Family:
  • Belongs to the S100-fused protein family.
genes like me logo Genes that share domains with FLG: view

Function for FLG Gene

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  2. CRISPR
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Molecular function for FLG Gene

UniProtKB/Swiss-Prot Function:
Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.
UniProtKB/Swiss-Prot Induction:
In cultured foreskin fibroblasts, up-regulated in response to Ca(2+) stimulation.
GENATLAS Biochemistry:
filaggrin,44kDa,intermediate filament associated protein (IFAP,type I),expressed in the horny layer of stratified epithelia,aggregating keratin filaments and promoting disulfite-bonding,component of the epidermal differentiation complex (EDC@)

Phenotypes From GWAS Catalog for FLG Gene

Gene Ontology (GO) - Molecular Function for FLG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005198 structural molecule activity NAS 2740331
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 23629652
GO:0030280 structural constituent of epidermis IBA,IDA 7543090
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with FLG: view
genes like me logo Genes that share phenotypes with FLG: view

Human Phenotype Ontology for FLG Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

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miRNA for FLG Gene

miRTarBase miRNAs that target FLG

Clone Products

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

Localization for FLG Gene

Subcellular locations from UniProtKB/Swiss-Prot for FLG Gene

Cytoplasmic granule. Note=In the stratum granulosum of the epidermis, localized within keratohyalin granules (PubMed:1429717). In granular keratinocytes and in lower corneocytes, colocalizes with calpain-1/CAPN1 (PubMed:21531719). {ECO:0000269 PubMed:1429717, ECO:0000269 PubMed:21531719}.

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 FLG gene
Compartment Confidence
cytoskeleton 5
plasma membrane 4
cytosol 4
nucleus 3
extracellular 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FLG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001533 cornified envelope IDA 7543090
GO:0005634 nucleus HDA 21630459
GO:0005829 cytosol TAS --
GO:0005882 intermediate filament NAS 2740331
GO:0036457 keratohyalin granule IDA,IBA 1429717
genes like me logo Genes that share ontologies with FLG: view

Pathways & Interactions for FLG Gene

PathCards logo

SuperPathways for FLG Gene

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

Pathways by source for FLG Gene

SIGNOR curated interactions for FLG Gene

Is activated by:

Gene Ontology (GO) - Biological Process for FLG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development NAS 2740331
GO:0018149 peptide cross-linking IDA 7543090
GO:0030216 keratinocyte differentiation TAS 17704059
GO:0061436 establishment of skin barrier IBA,IEP 23403047
GO:0070268 cornification TAS --
genes like me logo Genes that share ontologies with FLG: view

Drugs & Compounds for FLG Gene

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(20) Drugs for FLG Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(10) Additional Compounds for FLG Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FLG: view

Transcripts for FLG Gene

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for FLG Gene

(1) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(7) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

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

No ASD Table

Relevant External Links for FLG Gene

GeneLoc Exon Structure for
FLG
ECgene alternative splicing isoforms for
FLG

Expression for FLG Gene

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  1. Primer
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FLG Gene

mRNA expression in normal human tissues for FLG Gene
mRNA expression by GTEx for FLG GenemRNA expression by BioGPS for FLG Gene

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

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x31.1) and Skin - Not Sun Exposed (Suprapubic) (x17.7).

Protein differential expression in normal tissues from HIPED for FLG Gene

This gene is overexpressed in Urinary Bladder (31.0) and Skin (12.5).

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



NURSA nuclear receptor signaling pathways regulating expression of FLG Gene:

FLG

SOURCE GeneReport for Unigene cluster for FLG Gene:

Hs.654510

mRNA Expression by UniProt/SwissProt for FLG Gene:

P20930-FILA_HUMAN
Tissue specificity: Expressed in skin, thymus, stomach, tonsils, testis, placenta, kidney, pancreas, mammary gland, bladder, thyroid, salivary gland and trachea, but not detected in heart, brain, liver, lung, bone marrow, small intestine, spleen, prostate, colon, or adrenal gland (PubMed:19384417). In the skin, mainly expressed in stratum granulosum of the epidermis (PubMed:1429717) (PubMed:19384417).

Evidence on tissue expression from TISSUES for FLG Gene

  • Skin(4.7)
  • Liver(4.1)
  • Blood(2)

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

Germ Layers:
  • ectoderm
Systems:
  • integumentary
Regions:
General:
  • skin
genes like me logo Genes that share expression patterns with FLG: view

No data available for Protein tissue co-expression partners for FLG Gene

Orthologs for FLG Gene

This gene was present in the common ancestor of chordates.

Orthologs for FLG Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia FLG 33 32
  • 92.7 (n)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 33
  • 22 (a)
 OneToMany
oppossum
(Monodelphis domestica)
 Mammalia FLG 33
  • 19 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves CRNN 33
  • 16 (a)
 OneToMany
lizard
(Anolis carolinensis)
 Reptilia -- 33
  • 13 (a)
 OneToMany
Species where no ortholog for FLG was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • cow (Bos Taurus)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • mouse (Mus musculus)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for FLG Gene

ENSEMBL:
Gene Tree for FLG (if available)
TreeFam:
Gene Tree for FLG (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FLG: view image

Paralogs for FLG Gene

Paralogs for FLG Gene

(10) SIMAP similar genes for FLG Gene using alignment to 14 proteins:

  • FILA_HUMAN
  • I0B0K3_HUMAN
  • I0B0K4_HUMAN
  • I0B0K5_HUMAN
  • I0B0K6_HUMAN
  • I0B0K7_HUMAN
  • I0B0K8_HUMAN
  • L8E7P6_HUMAN
  • Q03837_HUMAN
  • Q03838_HUMAN
  • Q03839_HUMAN
  • Q15206_HUMAN
  • Q16824_HUMAN
  • Q4JFL9_HUMAN
genes like me logo Genes that share paralogs with FLG: view

Variants for FLG Gene

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Sequence variations from dbSNP and Humsavar for FLG Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1060499587 likely-pathogenic, Ichthyosis vulgaris 152,313,983(-) CCTGTCCTG/CCTG coding_sequence_variant, frameshift
rs114733570 pathogenic, not provided, Ichthyosis vulgaris 152,315,363(-) C/A coding_sequence_variant, stop_gained
rs1214424848 pathogenic, not provided, Dermatitis, atopic, 2, Ichthyosis vulgaris 152,314,399(-) C/A/T coding_sequence_variant, missense_variant, stop_gained
rs1218912272 pathogenic, Abnormality of salivation, Abnormality of the skin, Congenital cerebellar hypoplasia, Dry skin, Feeding difficulties, Ichthyosis, Microcephaly, Paroxysmal dystonia 152,314,342(-) T/A coding_sequence_variant, stop_gained
rs121909626 pathogenic, risk-factor, Ichthyosis vulgaris, Dermatitis, atopic, 2, susceptibility to 152,307,225(-) G/C/T coding_sequence_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for FLG Gene

Variant ID Type Subtype PubMed ID
esv1003613 OTHER inversion 20482838
esv1330223 CNV deletion 17803354
esv25681 CNV loss 19812545
esv2665362 CNV deletion 23128226
esv2669572 CNV deletion 23128226
esv2671163 CNV deletion 23128226
esv2718117 CNV deletion 23290073
esv2718128 CNV deletion 23290073
esv3394198 CNV duplication 20981092
esv3587546 CNV gain 21293372
nsv1014095 CNV gain 25217958
nsv1110152 CNV duplication 24896259
nsv1115370 CNV duplication 24896259
nsv1152559 CNV duplication 26484159
nsv159623 CNV deletion 16902084
nsv471348 CNV gain 19718026
nsv7183 OTHER inversion 18451855
nsv821364 CNV duplication 20802225
nsv824653 CNV loss 20364138
nsv952208 CNV deletion 24416366
nsv998298 CNV loss 25217958

Variation tolerance for FLG Gene

Residual Variation Intolerance Score: 100% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 27.35; 99.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FLG Gene

Human Gene Mutation Database (HGMD)
FLG
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FLG

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FLG Gene

Disorders for FLG Gene

MalaCards: The human disease database

(57) MalaCards diseases for FLG Gene - From: HGMD, OMIM, ClinVar, GTR, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ichthyosis vulgaris
  • ichthyosis simplex
dermatitis, atopic, 2
  • dermatitis, atopic
dermatitis, atopic
  • atod
paroxysmal dystonia
cerebellar hypoplasia
  • cerebellar hypoplasia-tapetoretinal degeneration syndrome
- elite association - COSMIC cancer census association via MalaCards
Search FLG in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FILA_HUMAN
  • Ichthyosis vulgaris (VI) [MIM:146700]: The most common form of ichthyosis inherited as an autosomal dominant trait. It is characterized by palmar hyperlinearity, keratosis pilaris and a fine scale that is most prominent over the lower abdomen, arms, and legs. Ichthyosis vulgaris is characterized histologically by absent or reduced keratohyalin granules in the epidermis and mild hyperkeratosis. The disease can be associated with frequent asthma, eczema or hay fever. {ECO:0000269 PubMed:16444271}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Dermatitis atopic 2 (ATOD2) [MIM:605803]: Atopic dermatitis is a complex, inflammatory disease with multiple alleles at several loci thought to be involved in the pathogenesis. It commonly begins in infancy or early childhood and is characterized by a chronic relapsing form of skin inflammation, a disturbance of epidermal barrier function that culminates in dry skin, and IgE-mediated sensitization to food and environmental allergens. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. {ECO:0000269 PubMed:16550169, ECO:0000269 PubMed:16815158, ECO:0000269 PubMed:17030239, ECO:0000269 PubMed:17291859}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for FLG

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FLG: view

No data available for Genatlas for FLG Gene

Publications for FLG Gene

  1. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. (PMID: 17291859) Nomura T … Shimizu H (The Journal of allergy and clinical immunology 2007) 3 4 23 43 56
  2. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. (PMID: 16815158) Weidinger S … Novak N (The Journal of allergy and clinical immunology 2006) 3 4 23 43 56
  3. Human leukocyte antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral responses to early food allergens in children. (PMID: 20016199) Savilahti EM … Savilahti E (International archives of allergy and immunology 2010) 3 23 43 56
  4. Chromosome 11q13.5 variant associated with childhood eczema: an effect supplementary to filaggrin mutations. (PMID: 20109745) O'Regan GM … Brown SJ (The Journal of allergy and clinical immunology 2010) 3 23 43 56
  5. Elder siblings enhance the effect of filaggrin mutations on childhood eczema: results from the 2 birth cohort studies LISAplus and GINIplus. (PMID: 20513523) Cramer C … LISAplus Study Group and the GINIplus Study Group (The Journal of allergy and clinical immunology 2010) 3 23 43 56

ExternalLinks

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