FLG2 filaggrin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FLG2provided by HGNC
Official Full Name: filaggrin 2provided by HGNC
Primary source: HGNC:HGNC:33276
See related: Ensembl:ENSG00000143520 MIM:616284; AllianceGenome:HGNC:33276
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IFPS; PSS6
Summary: 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 and E. coli. [provided by RefSeq, Jul 2020]
Expression: Restricted expression toward skin (RPKM 248.2) See more
Orthologs: all
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Genomic context

Location:: 1q21.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (152348735..152360006, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (151485285..151496556, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (152321211..152332482, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.
Title: Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.
Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort.
Title: Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort.
Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity.
Title: Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity.
Filaggrin and filaggrin 2 processing are linked together through skin aspartic acid protease activation.
Title: Filaggrin and filaggrin 2 processing are linked together through skin aspartic acid protease activation.
Data suggest that innate immunity of skin involves FLG2, which is expressed in high abundance in upper epidermis/eccrine sweat glands; C-terminal peptide fragments of FLG2 exhibit antimicrobial functions against replication of Pseudomonas aeruginosa and E. coli.
Title: Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication.
In a stop codon variant (rs12568784 G/T) in the FLG2 gene.
Title: Whole-exome sequencing indicates FLG2 variant associated with leg ulcers in Brazilian sickle cell anemia patients.
Study data demonstrate that FLG2 N-terminal part, including A-type repeats, is incorporated in cornified envelopes. Thus, FLG2 and FLG have overlapping roles in the homeostasis of the epidermal barrier.
Title: The Amino-Terminal Part of Human FLG2 Is a Component of Cornified Envelopes.
results demonstrate that GATA3 is involved in the regulation of filaggrin and filaggrin-2 expression during inflammatory conditions in the skin.
Title: GATA3 regulates FLG and FLG2 expression in human primary keratinocytes.
Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the peeling skin syndrome type A phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis.
Title: Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A.
sFGL2 levels are induced by HBV infection and correlated with the progression and clinical outcome of HBV-related liver diseases. Thus, sFGL2 may serve as a potential indicator for HBV-related liver diseases.
Title: Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Peeling skin syndrome 6 MedGen: C4748093 OMIM: 618084 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetic variants associated with disordered eating. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

D11S3114 (e-PCR)
- UniSTS:152207

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables structural molecule activity	IEA Inferred from Electronic Annotation more info
enables transition metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epidermis morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of skin barrier	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment of skin barrier	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
is_active_in cornified envelope	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in keratohyalin granule	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	HDA more info	PubMed
located_in tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: filaggrin-2

Names: filaggrin family member 2; ifapsoriasin; intermediate filament-associated and psoriasis susceptibility protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001014342.3 → NP_001014364.1 filaggrin-2

See identical proteins and their annotated locations for NP_001014364.1

Status: REVIEWED

Source sequence(s)

AL356504, AY827490, BC108269, BX095286

Consensus CDS

CCDS30861.1

UniProtKB/Swiss-Prot

Q5D862, Q9H4U1

Related

ENSP00000373370.4, ENST00000388718.5

Conserved Domains (1) summary

cd00213
Location:2 → 87

S-100; S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 ...