FLG
Filaggrin
Also known as: FILA_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P20930
- Gene
- FLG
- Ensembl
- ENSG00000143631
- Chromosome
- 1
- Canonical length
- 4061 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Cytoplasmic bodies
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
4061 residues, UniProt reviewed canonical sequence.
>P20930|FLG
1 MSTLLENIFA IINLFKQYSK KDKNTDTLSK KELKELLEKE FRQILKNPDD PDMVDVFMDH
61 LDIDHNKKID FTEFLLMVFK LAQAYYESTR KENLPISGHK HRKHSHHDKH EDNKQEENKE
121 NRKRPSSLER RNNRKGNKGR SKSPRETGGK RHESSSEKKE RKGYSPTHRE EEYGKNHHNS
181 SKKEKNKTEN TRLGDNRKRL SERLEEKEDN EEGVYDYENT GRMTQKWIQS GHIATYYTIQ
241 DEAYDTTDSL LEENKIYERS RSSDGKSSSQ VNRSRHENTS QVPLQESRTR KRRGSRVSQD
301 RDSEGHSEDS ERHSGSASRN HHGSAWEQSR DGSRHPRSHD EDRASHGHSA DSSRQSGTRH
361 AETSSRGQTA SSHEQARSSP GERHGSGHQQ SADSSRHSAT GRGQASSAVS DRGHRGSSGS
421 QASDSEGHSE NSDTQSVSGH GKAGLRQQSH QESTRGRSGE RSGRSGSSLY QVSTHEQPDS
481 AHGRTGTSTG GRQGSHHEQA RDSSRHSASQ EGQDTIRGHP GSSRGGRQGS HHEQSVNRSG
541 HSGSHHSHTT SQGRSDASHG QSGSRSASRQ TRNEEQSGDG TRHSGSRHHE ASSQADSSRH
601 SQVGQGQSSG PRTSRNQGSS VSQDSDSQGH SEDSERWSGS ASRNHHGSAQ EQSRDGSRHP
661 RSHHEDRAGH GHSADSSRKS GTRHTQNSSS GQAASSHEQA RSSAGERHGS RHQLQSADSS
721 RHSGTGHGQA SSAVRDSGHR GSSGSQATDS EGHSEDSDTQ SVSGHGQAGH HQQSHQESAR
781 DRSGERSRRS GSFLYQVSTH KQSESSHGWT GPSTGVRQGS HHEQARDNSR HSASQDGQDT
841 IRGHPGSSRR GRQGSHHEQS VDRSGHSGSH HSHTTSQGRS DASRGQSGSR SASRTTRNEE
901 QSRDGSRHSG SRHHEASSHA DISRHSQAGQ GQSEGSRTSR RQGSSVSQDS DSEGHSEDSE
961 RWSGSASRNH RGSAQEQSRH GSRHPRSHHE DRAGHGHSAD SSRQSGTPHA ETSSGGQAAS
1021 SHEQARSSPG ERHGSRHQQS ADSSRHSGIP RRQASSAVRD SGHWGSSGSQ ASDSEGHSEE
1081 SDTQSVSGHG QDGPHQQSHQ ESARDWSGGR SGRSGSFIYQ VSTHEQSESA HGRTRTSTGR
1141 RQGSHHEQAR DSSRHSASQE GQDTIRAHPG SRRGGRQGSH HEQSVDRSGH SGSHHSHTTS
1201 QGRSDASHGQ SGSRSASRQT RKDKQSGDGS RHSGSRHHEA ASWADSSRHS QVGQEQSSGS
1261 RTSRHQGSSV SQDSDSERHS DDSERLSGSA SRNHHGSSRE QSRDGSRHPG FHQEDRASHG
1321 HSADSSRQSG THHTESSSHG QAVSSHEQAR SSPGERHGSR HQQSADSSRH SGIGHRQASS
1381 AVRDSGHRGS SGSQVTNSEG HSEDSDTQSV SAHGQAGPHQ QSHKESARGQ SGESSGRSRS
1441 FLYQVSSHEQ SESTHGQTAP STGGRQGSRH EQARNSSRHS ASQDGQDTIR GHPGSSRGGR
1501 QGSYHEQSVD RSGHSGYHHS HTTPQGRSDA SHGQSGPRSA SRQTRNEEQS GDGSRHSGSR
1561 HHEPSTRAGS SRHSQVGQGE SAGSKTSRRQ GSSVSQDRDS EGHSEDSERR SESASRNHYG
1621 SAREQSRHGS RNPRSHQEDR ASHGHSAESS RQSGTRHAET SSGGQAASSQ EQARSSPGER
1681 HGSRHQQSAD SSTDSGTGRR QDSSVVGDSG NRGSSGSQAS DSEGHSEESD TQSVSAHGQA
1741 GPHQQSHQES TRGQSGERSG RSGSFLYQVS THEQSESAHG RTGPSTGGRQ RSRHEQARDS
1801 SRHSASQEGQ DTIRGHPGSS RGGRQGSHYE QSVDSSGHSG SHHSHTTSQE RSDVSRGQSG
1861 SRSVSRQTRN EKQSGDGSRH SGSRHHEASS RADSSRHSQV GQGQSSGPRT SRNQGSSVSQ
1921 DSDSQGHSED SERWSGSASR NHLGSAWEQS RDGSRHPGSH HEDRAGHGHS ADSSRQSGTR
1981 HTESSSRGQA ASSHEQARSS AGERHGSHHQ LQSADSSRHS GIGHGQASSA VRDSGHRGYS
2041 GSQASDSEGH SEDSDTQSVS AQGKAGPHQQ SHKESARGQS GESSGRSGSF LYQVSTHEQS
2101 ESTHGQSAPS TGGRQGSHYD QAQDSSRHSA SQEGQDTIRG HPGPSRGGRQ GSHQEQSVDR
2161 SGHSGSHHSH TTSQGRSDAS RGQSGSRSAS RKTYDKEQSG DGSRHSGSHH HEASSWADSS
2221 RHSLVGQGQS SGPRTSRPRG SSVSQDSDSE GHSEDSERRS GSASRNHHGS AQEQSRDGSR
2281 HPRSHHEDRA GHGHSAESSR QSGTHHAENS SGGQAASSHE QARSSAGERH GSHHQQSADS
2341 SRHSGIGHGQ ASSAVRDSGH RGSSGSQASD SEGHSEDSDT QSVSAHGQAG PHQQSHQEST
2401 RGRSAGRSGR SGSFLYQVST HEQSESAHGR TGTSTGGRQG SHHKQARDSS RHSTSQEGQD
2461 TIHGHPGSSS GGRQGSHYEQ LVDRSGHSGS HHSHTTSQGR SDASHGHSGS RSASRQTRND
2521 EQSGDGSRHS GSRHHEASSR ADSSGHSQVG QGQSEGPRTS RNWGSSFSQD SDSQGHSEDS
2581 ERWSGSASRN HHGSAQEQLR DGSRHPRSHQ EDRAGHGHSA DSSRQSGTRH TQTSSGGQAA
2641 SSHEQARSSA GERHGSHHQQ SADSSRHSGI GHGQASSAVR DSGHRGYSGS QASDNEGHSE
2701 DSDTQSVSAH GQAGSHQQSH QESARGRSGE TSGHSGSFLY QVSTHEQSES SHGWTGPSTR
2761 GRQGSRHEQA QDSSRHSASQ DGQDTIRGHP GSSRGGRQGY HHEHSVDSSG HSGSHHSHTT
2821 SQGRSDASRG QSGSRSASRT TRNEEQSGDG SRHSGSRHHE ASTHADISRH SQAVQGQSEG
2881 SRRSRRQGSS VSQDSDSEGH SEDSERWSGS ASRNHHGSAQ EQLRDGSRHP RSHQEDRAGH
2941 GHSADSSRQS GTRHTQTSSG GQAASSHEQA RSSAGERHGS HHQQSADSSR HSGIGHGQAS
3001 SAVRDSGHRG YSGSQASDNE GHSEDSDTQS VSAHGQAGSH QQSHQESARG RSGETSGHSG
3061 SFLYQVSTHE QSESSHGWTG PSTRGRQGSR HEQAQDSSRH SASQYGQDTI RGHPGSSRGG
3121 RQGYHHEHSV DSSGHSGSHH SHTTSQGRSD ASRGQSGSRS ASRTTRNEEQ SGDSSRHSVS
3181 RHHEASTHAD ISRHSQAVQG QSEGSRRSRR QGSSVSQDSD SEGHSEDSER WSGSASRNHR
3241 GSVQEQSRHG SRHPRSHHED RAGHGHSADR SRQSGTRHAE TSSGGQAASS HEQARSSPGE
3301 RHGSRHQQSA DSSRHSGIPR GQASSAVRDS RHWGSSGSQA SDSEGHSEES DTQSVSGHGQ
3361 AGPHQQSHQE SARDRSGGRS GRSGSFLYQV STHEQSESAH GRTRTSTGRR QGSHHEQARD
3421 SSRHSASQEG QDTIRGHPGS SRRGRQGSHY EQSVDRSGHS GSHHSHTTSQ GRSDASRGQS
3481 GSRSASRQTR NDEQSGDGSR HSWSHHHEAS TQADSSRHSQ SGQGQSAGPR TSRNQGSSVS
3541 QDSDSQGHSE DSERWSGSAS RNHRGSAQEQ SRDGSRHPTS HHEDRAGHGH SAESSRQSGT
3601 HHAENSSGGQ AASSHEQARS SAGERHGSHH QQSADSSRHS GIGHGQASSA VRDSGHRGSS
3661 GSQASDSEGH SEDSDTQSVS AHGQAGPHQQ SHQESTRGRS AGRSGRSGSF LYQVSTHEQS
3721 ESAHGRAGPS TGGRQGSRHE QARDSSRHSA SQEGQDTIRG HPGSRRGGRQ GSYHEQSVDR
3781 SGHSGSHHSH TTSQGRSDAS HGQSGSRSAS RETRNEEQSG DGSRHSGSRH HEASTQADSS
3841 RHSQSGQGES AGSRRSRRQG SSVSQDSDSE AYPEDSERRS ESASRNHHGS SREQSRDGSR
3901 HPGSSHRDTA SHVQSSPVQS DSSTAKEHGH FSSLSQDSAY HSGIQSRGSP HSSSSYHYQS
3961 EGTERQKGQS GLVWRHGSYG SADYDYGESG FRHSQHGSVS YNSNPVVFKE RSDICKASAF
4021 GKDHPRYYAT YINKDPGLCG HSSDISKQLG FSQSQRYYYY ELocalizationUniProt · AlphaFold · HPA
Whether an antibody against FLG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0
- Highest tissue expression
- 433 nTPM
Expression across tissuesHPA
Tissue
- skin: 433 nTPM
- breast: 15 nTPM
- esophagus: 12 nTPM
- cervix: 8.4 nTPM
- vagina: 3.7 nTPM
- salivary gland: 2.7 nTPM
Single-cell type
- esophageal apical cells: 1,978 nCPM
- cardiomyocytes: 40 nCPM
- esophageal suprabasal cells: 32 nCPM
- epicardial cells: 25 nCPM
- suprabasal keratinocytes: 25 nCPM
- retinal ganglion cells: 7.7 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- medulla oblongata: 6.1 nTPM
- hypothalamus: 5.5 nTPM
- pons: 5.1 nTPM
- midbrain: 4.5 nTPM
- thalamus: 4.3 nTPM
- spinal cord: 4.2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about FLG.
Disease | AllUniProt
Conditions FLG is implicated in, by any mechanism.
- Ichthyosis vulgaris (VI) MIM:146700
- Dermatitis atopic 2 (ATOD2) MIM:605803
Disease | GeneticClinVar
246 pathogenic / likely-pathogenic of 2,170 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Ichthyosis vulgaris
- Dermatitis, atopic, 2
- Inborn genetic diseases
- FLG-related disorder
- Autosomal dominant ichthyosis vulgaris
Disease | ImmuneIEDB
Conditions an epitope on FLG was assayed in.
- rheumatoid arthritis B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against FLG are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for FLG from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
50 publications
- The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin.
2001 · J Immunol · RCR 12 · 524 citations - The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues.
1999 · J Immunol · RCR 8.4 · 368 citations - The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.
1995 · J Clin Invest · RCR 7.1 · 259 citations - Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset.
2000 · Arthritis Res · RCR 6.8 · 271 citations - Prognostic factors in early rheumatoid arthritis.
2000 · Rheumatology (Oxford) · RCR 3.8 · 130 citations
Show 20 more of 50 total
- In the rheumatoid pannus, anti-filaggrin autoantibodies are produced by local plasma cells and constitute a higher proportion of IgG than in synovial fluid and serum.
2000 · Clin Exp Immunol · RCR 3.7 · 166 citations - Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies.
2001 · Arthritis Rheum · RCR 3.2 · 137 citations - Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis.
2002 · Arthritis Rheum · RCR 3.1 · 125 citations - High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis.
2003 · Scand J Rheumatol · RCR 3.1 · 120 citations - Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis.
2016 · Arthritis Res Ther · RCR 2.7 · 66 citations - Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases.
2004 · Ann Rheum Dis · RCR 2.5 · 86 citations - Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis.
2004 · Clin Exp Immunol · RCR 2.1 · 69 citations - Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis.
2005 · Ann N Y Acad Sci · RCR 2.1 · 71 citations - Detection of antibodies to deiminated recombinant rat filaggrin by enzyme-linked immunosorbent assay: a highly effective test for the diagnosis of rheumatoid arthritis.
2002 · Arthritis Rheum · RCR 1.9 · 75 citations - Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis.
1998 · J Rheumatol · RCR 1.8 · 64 citations - Anti-perinuclear factor compared with the so called "antikeratin" antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides.
1999 · Ann Rheum Dis · RCR 1.7 · 63 citations - Identification of citrullinated rheumatoid arthritis-specific epitopes in natural filaggrin relevant for antifilaggrin autoantibody detection by line immunoassay.
2002 · Arthritis Rheum · RCR 1.7 · 66 citations - Antifilaggrin antibodies within "normal" range predict rheumatoid arthritis in a linear fashion.
2000 · J Rheumatol · RCR 1.6 · 71 citations - Antifilaggrin antibodies in recent-onset arthritis.
1999 · Scand J Rheumatol · RCR 1.4 · 35 citations - Anti-citrullinated protein antibodies in rheumatoid arthritis: as good as it gets?
2008 · Clin Rev Allergy Immunol · RCR 1.4 · 55 citations - Abnormal distribution of epidermal protein antigens in psoriatic epidermis.
1991 · J Dermatol · RCR 1.4 · 49 citations - Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibodies in sera from patients with rheumatoid arthritis by an enzyme-linked immunosorbent assay.
1998 · Int Arch Allergy Immunol · RCR 1.3 · 43 citations - Association of rheumatoid factors and anti-filaggrin antibodies with severity of erosions in rheumatoid arthritis.
2000 · Rheumatology (Oxford) · RCR 1.1 · 43 citations - Performance of two ELISAs for antifilaggrin autoantibodies, using either affinity purified or deiminated recombinant human filaggrin, in the diagnosis of rheumatoid arthritis.
2001 · Ann Rheum Dis · RCR 1 · 41 citations - Cytokine and chemokine receptor profile of peripheral blood mononuclear cells during treatment with infliximab in patients with active rheumatoid arthritis.
2004 · Ann Rheum Dis · RCR 1 · 41 citations
Reference: B cellIEDB
1 publication
- Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.96
- gnomAD pLI
- 0
- gnomAD missense Z
- -19
- DepMap mean gene effect
- 0.02
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FLG as an antibody target. Whether an autoantibody or antibody against FLG could matter depends on whether native FLG is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FLG is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label FLG as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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