The filaggrin-like protein encoded by this gene is upregulated by calcium, proteolyzed by calpain 1, and is involved in epithelial homeostasis. The encoded protein is required for proper cornification in skin, with defects in this gene being associated with skin diseases. This protein also has a function in skin barrier protection. In fact, in addition to providing a physical b... See more...

Aliases for FLG2 Gene

Aliases for FLG2 Gene

  • Filaggrin Family Member 2 2 3 5
  • Ifapsoriasin 3 4
  • Filaggrin-2 3 4
  • IFPS 3 4
  • Intermediate Filament-Associated And Psoriasis Susceptibility Protein 3
  • Intermediate Filament-Associated And Psoriasis-Susceptibility Protein 4
  • FLG-2 4
  • PSS6 3

External Ids for FLG2 Gene

Previous GeneCards Identifiers for FLG2 Gene

  • GC01M150588
  • GC01M123694

Summaries for FLG2 Gene

Entrez Gene Summary for FLG2 Gene

  • The filaggrin-like protein encoded by this gene is upregulated by calcium, proteolyzed by calpain 1, and is involved in epithelial homeostasis. The encoded protein is required for proper cornification in skin, with defects in this gene being associated with skin diseases. This protein also has a function in skin barrier protection. In fact, in addition to providing a physical barrier, C-terminal fragments of this protein display antimicrobial activity against P. aeruginosa. [provided by RefSeq, Dec 2015]

GeneCards Summary for FLG2 Gene

FLG2 (Filaggrin Family Member 2) is a Protein Coding gene. Diseases associated with FLG2 include Peeling Skin Syndrome 6 and Peeling Skin Syndrome Type A. Among its related pathways are Innate Immune System. Gene Ontology (GO) annotations related to this gene include calcium ion binding and structural molecule activity. An important paralog of this gene is FLG.

UniProtKB/Swiss-Prot Summary for FLG2 Gene

  • Essential for normal cell-cell adhesion in the cornified cell layers (PubMed:29758285). Important for proper integrity and mechanical strength of the stratum corneum of the epidermis (PubMed:29505760).

Additional gene information for FLG2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FLG2 Gene

Genomics for FLG2 Gene

GeneHancer (GH) Regulatory Elements for FLG2 Gene

Promoters and enhancers for FLG2 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
GH01J152392 Enhancer 1 Ensembl ENCODE 11.1 -33.1 -33091 1 ZNF217 KLF4 KLF7 CUX1 CHD1 ZNF662 GATAD2B CTBP1 ZNF148 OSR2 MRPL9 POGZ FLG HRNR FLG2 HMGN3P1 L13713-016 FLG-AS1
GH01J152458 Enhancer 0.6 ENCODE 10.1 -98.6 -98570 0.2 ZNF217 CTCF RAD21 TRIM22 SMC3 ZNF341 DEK PKNOX1 ZNF654 RFX5 FLG2 CRCT1 RPTN piR-61532-019 piR-61514-019
GH01J152446 Enhancer 0.4 dbSUPER 10.3 -88.9 -88915 5.4 CTCF RAD21 HNF4A ZNF579 MYC FLG S100A11 CRNN FLG2 HRNR FLG-AS1 piR-61514-019 piR-61532-019
GH01J152229 Enhancer 0.4 Ensembl ENCODE 9.6 +130.9 130909 0.2 FOS ENSG00000236427 FLG TCHH FLG2 HRNR piR-60031-008 FLG-AS1
GH01J152426 Enhancer 0.3 dbSUPER 10.7 -67.7 -67697 1.6 ZFX FOS FLG CRNN FLG2 HRNR RPTN piR-61514-019 piR-47176-001 FLG-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FLG2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FLG2

Top Transcription factor binding sites by QIAGEN in the FLG2 gene promoter:
  • AML1a
  • CBF(2)
  • CBF-A
  • CBF-B
  • CBF-C
  • CP1A
  • CP1C
  • ISGF-3
  • NF-Y
  • NF-YA

Genomic Locations for FLG2 Gene

Genomic Locations for FLG2 Gene
chr1:152,348,735-152,360,010
(GRCh38/hg38)
Size:
11,276 bases
Orientation:
Minus strand
chr1:152,321,211-152,332,482
(GRCh37/hg19)
Size:
11,272 bases
Orientation:
Minus strand

Genomic View for FLG2 Gene

Genes around FLG2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FLG2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FLG2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FLG2 Gene

Proteins for FLG2 Gene

  • Protein details for FLG2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5D862-FILA2_HUMAN
    Recommended name:
    Filaggrin-2
    Protein Accession:
    Q5D862
    Secondary Accessions:
    • Q9H4U1

    Protein attributes for FLG2 Gene

    Size:
    2391 amino acids
    Molecular mass:
    248073 Da
    Quaternary structure:
    No Data Available

neXtProt entry for FLG2 Gene

Post-translational modifications for FLG2 Gene

  • Deiminated by PADI1, PADI2 or PADI3 in vitro. The deiminated form is degraded by calpain-1/CAPN1 more quickly and into shorter peptides than the intact protein.
  • May be processed by calpain-1/CAPN1 in the uppermost epidermal layers.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FLG2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FLG2 Gene

Domains & Families for FLG2 Gene

Gene Families for FLG2 Gene

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

Protein Domains for FLG2 Gene

Blocks:
  • Serine protease, trypsin family
  • Calcium-binding protein, S-100/ICaBP type
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FLG2 Gene

GenScript: Design optimal peptide antigens:
  • Intermediate filament-associated and psoriasis-susceptibility protein (FILA2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5D862

UniProtKB/Swiss-Prot:

FILA2_HUMAN :
  • Belongs to the S100-fused protein family.
Family:
  • Belongs to the S100-fused protein family.
  • In the N-terminal section; belongs to the S-100 family.
genes like me logo Genes that share domains with FLG2: view

Function for FLG2 Gene

Molecular function for FLG2 Gene

UniProtKB/Swiss-Prot Function:
Essential for normal cell-cell adhesion in the cornified cell layers (PubMed:29758285). Important for proper integrity and mechanical strength of the stratum corneum of the epidermis (PubMed:29505760).
UniProtKB/Swiss-Prot Induction:
In cultured foreskin fibroblasts, up-regulated in response to Ca(2+) stimulation.

Phenotypes From GWAS Catalog for FLG2 Gene

Gene Ontology (GO) - Molecular Function for FLG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005198 structural molecule activity IEA --
GO:0005509 calcium ion binding IEA --
GO:0046872 metal ion binding IEA --
GO:0046914 transition metal ion binding IEA --
genes like me logo Genes that share ontologies with FLG2: view
genes like me logo Genes that share phenotypes with FLG2: view

Human Phenotype Ontology for FLG2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for FLG2 Gene

Localization for FLG2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FLG2 Gene

Cytoplasm. Cytoplasmic granule. Note=In the stratum corneum of the epidermis, dispersed diffusely throughout the cytoplasm, while in the stratum granulosum, localized within keratohyalin granules (PubMed:19384417) (PubMed:21531719). In granular keratinocytes and in lower corneocytes, colocalizes with calpain-1/CAPN1. {ECO:0000269 PubMed:19384417, 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 FLG2 gene
Compartment Confidence
plasma membrane 4
extracellular 4
nucleus 3
cytosol 3
cytoskeleton 2
mitochondrion 1
peroxisome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for FLG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001533 cornified envelope IBA 21873635
GO:0005576 extracellular region TAS --
GO:0005634 nucleus HDA 21630459
GO:0005737 cytoplasm IDA,IEA 19384417
GO:0036457 keratohyalin granule IBA 21873635
genes like me logo Genes that share ontologies with FLG2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for FLG2 Gene

Pathways & Interactions for FLG2 Gene

PathCards logo

SuperPathways for FLG2 Gene

genes like me logo Genes that share pathways with FLG2: view

Pathways by source for FLG2 Gene

3 Reactome pathways for FLG2 Gene

Gene Ontology (GO) - Biological Process for FLG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007155 cell adhesion IMP 29758285
GO:0043312 neutrophil degranulation TAS --
GO:0048730 epidermis morphogenesis IMP 29505760
GO:0061436 establishment of skin barrier IBA,IEP 23403047
genes like me logo Genes that share ontologies with FLG2: view

No data available for SIGNOR curated interactions for FLG2 Gene

Drugs & Compounds for FLG2 Gene

No Compound Related Data Available

Transcripts for FLG2 Gene

mRNA/cDNA for FLG2 Gene

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

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FLG2 Gene

No ASD Table

Relevant External Links for FLG2 Gene

GeneLoc Exon Structure for
FLG2

Expression for FLG2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FLG2 Gene

mRNA differential expression in normal tissues according to GTEx for FLG2 Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x30.8) and Skin - Not Sun Exposed (Suprapubic) (x21.8).

Protein differential expression in normal tissues from HIPED for FLG2 Gene

This gene is overexpressed in Urinary Bladder (33.3), Bone (8.6), and Cerebrospinal fluid (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FLG2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FLG2

SOURCE GeneReport for Unigene cluster for FLG2 Gene:

Hs.156124

mRNA Expression by UniProt/SwissProt for FLG2 Gene:

Q5D862-FILA2_HUMAN
Tissue specificity: Expressed in skin, thymus, stomach and placenta, but not detected in heart, brain, liver, lung, bone marrow, small intestine, spleen, prostate, colon, adrenal gland, kidney, pancreas, mammary gland, bladder, thyroid, salivary gland and trachea. Weakly expressed in esophagus, tonsils and testis (at protein level). In the skin, strongly expressed in the upper stratum granulosum and lower stratum corneum, but not detected in the upper stratum corneum (at protein level) (PubMed:19384417) (PubMed:21531719). In scalp hair follicles, mainly restricted within the granular and cornified cells surrounding the infundibular outer root sheath, with weak expression in central and proximal outer root sheath (at protein level). Tends to be down-regulated in sporiatic lesions compared to non-lesional skin inthe same patients (PubMed:19384417).

Evidence on tissue expression from TISSUES for FLG2 Gene

  • Skin(4.8)
  • Liver(4.1)
  • Intestine(2.3)
  • Stomach(2)
genes like me logo Genes that share expression patterns with FLG2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for FLG2 Gene

Orthologs for FLG2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FLG2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FLG2 31
  • 48 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 31 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 26 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Flg2 31
  • 25 (a)
OneToOne
dog
(Canis familiaris)
Mammalia FLG2 31
  • 21 (a)
OneToOne
cow
(Bos Taurus)
Mammalia FLG2 31
  • 17 (a)
OneToOne
chicken
(Gallus gallus)
Aves CRNN 31
  • 16 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 13 (a)
OneToMany
Species where no ortholog for FLG2 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)
  • 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)
  • 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 FLG2 Gene

ENSEMBL:
Gene Tree for FLG2 (if available)
TreeFam:
Gene Tree for FLG2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FLG2: view image

Paralogs for FLG2 Gene

Paralogs for FLG2 Gene

(11) SIMAP similar genes for FLG2 Gene using alignment to 2 proteins:

  • FILA2_HUMAN
  • L8E7D3_HUMAN
genes like me logo Genes that share paralogs with FLG2: view

Variants for FLG2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FLG2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
806217 Uncertain Significance: not provided 152,354,073(-) GT/G FRAMESHIFT_VARIANT
806218 Likely Pathogenic: not provided 152,354,228(-) TG/T NONSENSE
rs1050823116 Pathogenic: Peeling skin syndrome 6 152,357,154(-) G/C NONSENSE
rs1553219199 Pathogenic: Peeling skin syndrome 6 152,356,721(-) A/T NONSENSE
rs12411129 - p.Ser958Tyr

Additional dbSNP identifiers (rs#s) for FLG2 Gene

Structural Variations from Database of Genomic Variants (DGV) for FLG2 Gene

Variant ID Type Subtype PubMed ID
dgv200n106 CNV duplication 24896259
esv2043587 CNV deletion 18987734
esv2593579 CNV deletion 19546169
esv2663079 CNV deletion 23128226
esv2664011 CNV deletion 23128226
esv2718140 CNV deletion 23290073
esv2718151 CNV deletion 23290073
esv3540790 CNV deletion 23714750
esv3578178 CNV loss 25503493
nsv1014095 CNV gain 25217958
nsv1075398 CNV duplication 25765185
nsv1147169 CNV duplication 26484159

Variation tolerance for FLG2 Gene

Residual Variation Intolerance Score: 77.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 16.95; 97.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FLG2 Gene

Human Gene Mutation Database (HGMD)
FLG2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FLG2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FLG2 Gene

Disorders for FLG2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for FLG2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
peeling skin syndrome 6
  • pss6
peeling skin syndrome type a
  • generalized deciduous skin type a
peeling skin syndrome
  • exfoliation syndrome
amyloid tumor
  • amyloid neoplasm
intussusception
  • intussusception of intestine
- elite association - COSMIC cancer census association via MalaCards
Search FLG2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FILA2_HUMAN
  • Peeling skin syndrome 6 (PSS6) [MIM:618084]: A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS6 patients manifest generalized ichthyotic dry skin, and bullous peeling lesions on the trunk and limbs at sites of minor trauma. Skin symptoms are exacerbated by warmth and humidity. PSS6 inheritance is autosomal recessive. {ECO:0000269 PubMed:28884927, ECO:0000269 PubMed:29505760, ECO:0000269 PubMed:29758285}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for FLG2

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 FLG2: view

No data available for Genatlas for FLG2 Gene

Publications for FLG2 Gene

  1. Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family. (PMID: 19384417) Wu Z … Schröder JM (PloS one 2009) 2 3 4 23 54
  2. Generalized Ichthyotic Peeling Skin Syndrome due to FLG2 Mutations. (PMID: 29505760) Bolling MC … Jonkman MF (The Journal of investigative dermatology 2018) 3 4 54
  3. Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A. (PMID: 29758285) Mohamad J … Sprecher E (The Journal of investigative dermatology 2018) 3 4 54
  4. Deimination of human filaggrin-2 promotes its proteolysis by calpain 1. (PMID: 21531719) Hsu CY … Simon M (The Journal of biological chemistry 2011) 3 4 54
  5. Variation in genes of the epidermal differentiation complex in German atopic dermatitis patients. (PMID: 19601998) Stemmler S … Hoffjan S (International journal of immunogenetics 2009) 3 41 54

Products for FLG2 Gene

Sources for FLG2 Gene