FLG2 (Filaggrin 2)
Gene encoding filaggrin family member 2, involved in skin barrier function and associated with atopic dermatitis and ichthyosis vulgaris.
Gene Information Card
| Symbol | FLG2 |
|---|---|
| Full Name | Filaggrin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 388698 ncbi.nlm.nih.gov/gene/388698 |
| Ensembl ID | ENSG00000143546 |
| UniProt ID | Q5D862 |
| OMIM ID | 616284 |
| HGNC ID | 33276 |
| Aliases | FLG2, filaggrin-2, IFPS, profilaggrin 2 |
Description
FLG2 encodes filaggrin 2, a member of the filaggrin family of proteins that are critical for epidermal differentiation and skin barrier function. Filaggrin 2 is expressed in the granular layer of the epidermis and contributes to the aggregation of keratin filaments, formation of the cornified envelope, and maintenance of skin hydration. Loss-of-function mutations in FLG2 are associated with ichthyosis vulgaris and atopic dermatitis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ichthyosis vulgaris | Loss-of-function mutations impair filaggrin 2 function, leading to defective skin barrier and scaling. | OMIM #146700; PMID: 24387990 |
| Atopic dermatitis | FLG2 mutations reduce filaggrin 2 expression, compromising epidermal barrier and increasing allergen penetration. | ClinVar; PMID: 24387990 |
| Psoriasis | Altered FLG2 expression observed in psoriatic skin, but direct causal mutations not established. | PMID: 22903689 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 56.3 | High |
| Esophagus | 12.1 | Medium |
| Oral mucosa | 8.5 | Medium |
| Vagina | 6.2 | Low |
| Other tissues | <1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 45.2 | High expression in differentiated keratinocytes |
| NHEK (normal human epidermal keratinocytes) | 38.7 | High expression upon calcium-induced differentiation |
| A431 (epidermoid carcinoma) | 22.1 | Moderate expression |
| HeLa | 0.5 | Negligible |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3321delA | Frameshift | Rare (0.1% in European populations) | Loss of function; associated with ichthyosis vulgaris |
| c.658C>T (p.Arg220*) | Nonsense | 0.05% in East Asian populations | Premature stop; loss of function; linked to atopic dermatitis |
| c.2282_2285del | Frameshift | 0.02% in African populations | Loss of function; reported in ichthyosis vulgaris |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in FLG2 lead to truncated or absent filaggrin 2 protein, impairing skin barrier integrity.
Gain of Function (GOF)
No gain-of-function mutations reported for FLG2.
Dominant Negative (DN)
No dominant-negative mutations described for FLG2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG: hsa04540 (Gap junction)
• Reactome: R-HSA-6809371 (Formation of the cornified envelope)
• Reactome: R-HSA-1266738 (Developmental biology)
Protein Summary
Filaggrin 2 is a 2481-amino acid protein (UniProt Q5D862) that undergoes proteolytic processing from profilaggrin 2 to active filaggrin 2. It contains multiple filaggrin repeats and a calcium-binding EF-hand domain. The protein aggregates keratin intermediate filaments in the stratum corneum, contributing to the mechanical strength and hydration of the skin. Loss of filaggrin 2 function disrupts the epidermal barrier, predisposing to inflammatory skin diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FLG2 Knockout HEK293 Cell Line | EDJ-KQ12741 | Human | 388698 | Details Get a Quote |
| FLG2 Knockout HeLa Cell Line | EDJ-KQ60046 | Human | 388698 | Details Get a Quote |
| FLG2 Knockout A-549 Cell Line | EDJ-KQ68509 | Human | 388698 | Details Get a Quote |
| FLG2 Knockout HCT 116 Cell Line | EDJ-KQ76884 | Human | 388698 | Details Get a Quote |
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