GeneBe

FLG2

protein-coding

filaggrin 2, the group of S100 fused type protein family|EF-hand domain containing

Gene 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]

MANE transcript

NM_001014342.3

Inheritance

AR

ClinVar variants

P:7U:330B:81

Top phenotype

Peeling skin syndrome 6

gnomAD constraint

pLI —, LoF o/e 1.38

Max pathogenic AF

—

Genomic locus

chr1:152,348,735-152,360,006

External References & Databases

Ensembl (ENSG00000143520)NCBI Gene (388698)OMIM (616284)HGNC:33276GenCCUniProt (Q5D862)AlphaFoldClinVar (FLG2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

peeling skin syndrome 6LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054852

Submitter: Ambry Genetics

peeling skin syndrome type ASUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014555

Submitter: Orphanet

peeling skin syndrome 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054852

Submitter: PanelApp Australia

peeling skin syndrome 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054852

Submitter: Labcorp Genetics (formerly Invitae)

peeling skin syndrome 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054852

Submitter: Genomics England PanelApp

peeling skin syndrome 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054852

Submitter: G2P

Clinical Genomic Database (CGD)

Peeling skin syndrome 6AR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28884927; 29505760; 29758285Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FLG2 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 371
not providedTotal: 55
Peeling skin syndrome 6Total: 9
FLG2-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001014342.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
32
clinvar
2
clinvar
 35
missense
323
clinvar
42
clinvar
5
clinvar
 370
nonsense
1
clinvar
3
clinvar
1
clinvar
 5
start loss
0
frameshift
3
clinvar
5
clinvar
 8
splice donor/acceptor (+/-2bp)
0
Total16330747418

Highest pathogenic variant AF is 0.0009932352

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001014342.3RefSeqNP_001014364.12MANE Select
ENST00000388718.5EnsemblENSP00000373370.42MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Neutrophil degranulation
  • Innate Immune System
  • Immune System

Biological Process

  • neutrophil degranulation
  • establishment of skin barrier

Molecular Function

  • calcium ion binding
  • structural constituent of epidermis
  • transition metal ion binding

Cellular Component

  • cornified envelope
  • extracellular region
  • nucleus
  • cytoplasm
  • keratohyalin granule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000388718
Coding exons
2
Length
11272
Individuals with no LoFs
125595
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125598
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.1912601.15e+31.100.000055215111
Missense (PolyPhen)121112.151.07891435
Synonymous-3.045234421.180.00002254939
Loss of Function-0.42721.451.386.00e-821

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool
0.982
RVIS EVS
2.28
RVIS percentile EVS
98.27

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0380

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
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