FLG2

Summary

FLG2 (filaggrin 2, HGNC:33276) is a protein-coding gene on chromosome 1q21.3, encoding Filaggrin-2 (Q5D862). Essential for normal cell-cell adhesion in the cornified cell layers.

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.

Source: NCBI Gene 388698 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peeling skin syndrome 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 36 total — 1 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• MANE Select transcript: NM_001014342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33276
Approved symbol	FLG2
Name	filaggrin 2
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFPS
Ensembl gene	ENSG00000143520
Ensembl biotype	protein_coding
OMIM	616284
Entrez	388698

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000388718

RefSeq mRNA: 1 — MANE Select: NM_001014342 NM_001014342

CCDS: CCDS30861

Canonical transcript exons

ENST00000388718 — 3 exons

Exon	Start	End
ENSE00001447972	152359956	152360006
ENSE00001503744	152348735	152357647
ENSE00001512764	152358747	152358906

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9434 / max 848.1511, expressed in 30 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14540	0.9434	30

Top tissues by expression

232 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.96	gold quality
skin of hip	UBERON:0001554	99.93	gold quality
penis	UBERON:0000989	99.61	gold quality
mammalian vulva	UBERON:0000997	99.61	gold quality
nipple	UBERON:0002030	99.19	gold quality
zone of skin	UBERON:0000014	97.40	gold quality
skin of leg	UBERON:0001511	97.39	gold quality
skin of abdomen	UBERON:0001416	96.77	gold quality
gingival epithelium	UBERON:0001949	69.48	gold quality
gingiva	UBERON:0001828	66.89	gold quality
amniotic fluid	UBERON:0000173	65.60	gold quality
buccal mucosa cell	CL:0002336	65.09	silver quality
lower lobe of lung	UBERON:0008949	56.55	silver quality
esophagus squamous epithelium	UBERON:0006920	56.35	silver quality
deltoid	UBERON:0001476	53.38	gold quality
gastrocnemius	UBERON:0001388	52.69	gold quality
bone marrow cell	CL:0002092	52.04	gold quality
lower esophagus mucosa	UBERON:0035834	51.77	gold quality
esophagus mucosa	UBERON:0002469	51.38	gold quality
heart left ventricle	UBERON:0002084	50.60	gold quality
cardiac ventricle	UBERON:0002082	50.24	gold quality
muscle of leg	UBERON:0001383	49.43	gold quality
palpebral conjunctiva	UBERON:0001812	48.65	gold quality
sural nerve	UBERON:0015488	48.32	gold quality
right atrium auricular region	UBERON:0006631	48.08	gold quality
popliteal artery	UBERON:0002250	48.01	gold quality
tibial artery	UBERON:0007610	47.95	gold quality
cardiac atrium	UBERON:0002081	47.88	gold quality
heart	UBERON:0000948	47.38	gold quality
epithelium of nasopharynx	UBERON:0001951	47.35	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting FLG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-1206	99.30	69.32	1016

Literature-anchored findings (GeneRIF, showing 16)

• FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors (PMID:19384417)
• calpain 1 is essential for the proteolytic processing of FLG2 and that deimination accelerates this process. (PMID:21531719)
• In an African American cohort with Atopic dermatitis (AD), FLG2 mutations were associated with more persistent AD. (PMID:24184149)
• These findings suggest that filaggrin-2 may play an overlapping role with filaggrin in epithelial cornification; however, it may also have a partially distinct role in the molecular processes of cornification. (PMID:24813994)
• 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. (PMID:26371476)
• results indicate that filaggrin-2 was expressed in the oral mucosa under certain pathological conditions ( lichen planus, leukokeratosis and leukoplakia), demonstrating that an aberrant protein expression, together with filaggrin, indicates the altered differentiation program including hyperkeratosis that occurs in these diseases. (PMID:26858109)
• Levels of FLG, FLG2 and SPRR3 mRNAs and proteins were reduced in AD skin. (PMID:27304082)
• results demonstrate that GATA3 is involved in the regulation of filaggrin and filaggrin-2 expression during inflammatory conditions in the skin. (PMID:28928464)
• 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. (PMID:29758285)
• 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. (PMID:30419833)
• 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. (PMID:30528829)
• In a stop codon variant (rs12568784 G/T) in the FLG2 gene. (PMID:31079484)
• Filaggrin and filaggrin 2 processing are linked together through skin aspartic acid protease activation. (PMID:32437351)
• Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity. (PMID:34543471)
• Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort. (PMID:34984527)
• Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization. (PMID:36930145)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Flg2	ENSMUSG00000049133
rattus_norvegicus		ENSRNOG00000064129

Paralogs (3): FLG (ENSG00000143631), HRNR (ENSG00000197915), RPTN (ENSG00000215853)

Protein

Protein identifiers

Filaggrin-2 — Q5D862 (reviewed: Q5D862)

Alternative names: Intermediate filament-associated and psoriasis-susceptibility protein

All UniProt accessions (1): Q5D862

UniProt curated annotations — full annotation on UniProt →

Function. Essential for normal cell-cell adhesion in the cornified cell layers. Important for proper integrity and mechanical strength of the stratum corneum of the epidermis.

Subcellular location. Cytoplasm. Cytoplasmic granule.

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). 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.

Post-translational modifications. 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.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. In cultured foreskin fibroblasts, up-regulated in response to Ca(2+) stimulation.

Similarity. Belongs to the S100-fused protein family. In the N-terminal section; belongs to the S-100 family.

RefSeq proteins (1): NP_001014364* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR003303	Filaggrin	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR034325	S-100_dom	Domain
IPR052503	S100-fused_Epidermal_Struct	Family

Pfam: PF01023

UniProt features (114 total): compositionally biased region 63, sequence variant 15, modified residue 14, repeat 10, binding site 5, region of interest 4, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5D862-F1	33.09	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 62; 64; 66; 68; 73

Post-translational modifications (14): 1276, 1427, 1428, 1504, 1505, 1579, 1656, 1657, 1800, 1807, 1883, 1884, 1959, 2034

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 60 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_EPIDERMIS_MORPHOGENESIS, GOCC_SECRETORY_GRANULE, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_SKIN_DEVELOPMENT, GOBP_TISSUE_MORPHOGENESIS, GOCC_SECRETORY_VESICLE, chr1q21, GOCC_CORNIFIED_ENVELOPE, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOCC_TERTIARY_GRANULE, GOCC_TERTIARY_GRANULE_LUMEN, REACTOME_NEUTROPHIL_DEGRANULATION

GO Biological Process (3): cell adhesion (GO:0007155), epidermis morphogenesis (GO:0048730), establishment of skin barrier (GO:0061436)

GO Molecular Function (4): structural molecule activity (GO:0005198), calcium ion binding (GO:0005509), transition metal ion binding (GO:0046914), metal ion binding (GO:0046872)

GO Cellular Component (6): cornified envelope (GO:0001533), extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), keratohyalin granule (GO:0036457), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metal ion binding	2
cellular process	1
morphogenesis of an epithelium	1
epidermis development	1
skin epidermis development	1
molecular_function	1
cation binding	1
plasma membrane	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

2351 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLG2	LORICRIN	P23490	997
FLG2	IVL	P07476	995
FLG2	KRT1	P04264	942
FLG2	KRT10	P13645	916
FLG2	CASP14	P31944	874
FLG2	SPINK5	Q9NQ38	872
FLG2	PADI3	Q9ULW8	846
FLG2	DSG1	Q02413	815
FLG2	TGM1	P22735	810
FLG2	KLK7	P49862	776
FLG2	TSLP	Q969D9	716
FLG2	ING1	Q9UK53	705
FLG2	TGM3	Q08188	705
FLG2	SPRR1A	P35321	703
FLG2	KRT5	P13647	699

IntAct

90 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
GMCL1	A2ML1	psi-mi:“MI:0914”(association)	0.530
E6	CASK	psi-mi:“MI:0914”(association)	0.520
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
YWHAE	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.400
JAK1	DSP	psi-mi:“MI:0914”(association)	0.350
Ckap5	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Ddb1	COPS6	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
CDK1	RBMXL2	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
VDAC1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
MAPT	NCAN	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS), FLG2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1M6T247, B3A0P1, C0J7L8, C4NZN9, H2A0K8, H2A0K9, H2A0M6, O18740, P02674, P04459, P05685, P05995, P06649, P07856, P08827, P08828, P08915, P08917, P0C8Z4, P12796, P13396, P19469, P19470, P27781, P50438, P54681, P86797, P86798, P86857, P86949, P86950, P86951, P86985, Q28201, Q42626, Q54GV8, Q54M35, Q5D862, Q6F4C6, Q6JHY2

Diamond homologs: A6QP92, P20930, P37709, P97347, Q07283, Q2VIS4, Q5D862, Q5QJ38, Q6XPR3, Q9D3P1, Q9UBG3, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05942, P05964, P06702, P06703, P07091, P10462, P14069, P23297, P24480, P25815, P26447, P27003, P28318, P28783, P29034, P29377, P30801, P33763, P33764

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	6	21.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	30
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4849429	NM_001014342.3(FLG2):c.58A>T (p.Lys20Ter)	Likely pathogenic

SpliceAI

212 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152358741:TCTCA:T	donor_loss	1.0000
1:152358742:CTCAC:C	donor_loss	1.0000
1:152358744:CAC:C	donor_loss	1.0000
1:152358746:C:CA	donor_loss	1.0000
1:152358902:TGAAC:T	acceptor_gain	1.0000
1:152358903:GAAC:G	acceptor_gain	1.0000
1:152358904:AAC:A	acceptor_gain	1.0000
1:152358905:AC:A	acceptor_gain	1.0000
1:152358906:CC:C	acceptor_gain	1.0000
1:152358907:C:CA	acceptor_loss	1.0000
1:152358907:C:CC	acceptor_gain	1.0000
1:152358912:C:CT	acceptor_gain	1.0000
1:152358914:C:CT	acceptor_gain	1.0000
1:152358915:A:T	acceptor_gain	1.0000
1:152357411:ATGT:A	donor_gain	0.9900
1:152358745:A:AC	donor_gain	0.9900
1:152358746:C:CC	donor_gain	0.9900
1:152358746:CCTT:C	donor_gain	0.9900
1:152358905:ACC:A	acceptor_gain	0.9900
1:152358906:CCT:C	acceptor_gain	0.9900
1:152358907:C:T	acceptor_gain	0.9900
1:152357414:T:TA	donor_gain	0.9800
1:152358904:AACC:A	acceptor_gain	0.9800
1:152358907:C:A	acceptor_gain	0.9800
1:152359950:TCTCA:T	donor_loss	0.9700
1:152359951:CTCA:C	donor_loss	0.9700
1:152359952:TCA:T	donor_loss	0.9700
1:152359953:CAC:C	donor_loss	0.9700
1:152359954:A:AT	donor_loss	0.9700
1:152359955:C:A	donor_loss	0.9700

AlphaMissense

15278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152357564:A:C	F74L	0.998
1:152357564:A:T	F74L	0.998
1:152357566:A:G	F74L	0.998
1:152357544:A:G	L81P	0.997
1:152357565:A:G	F74S	0.997
1:152358840:G:C	F15L	0.997
1:152358840:G:T	F15L	0.997
1:152358842:A:G	F15L	0.997
1:152358778:A:G	L36P	0.996
1:152358787:A:G	L33P	0.996
1:152357562:A:G	L75P	0.995
1:152357573:A:C	F71L	0.995
1:152357573:A:T	F71L	0.995
1:152357574:A:G	F71S	0.995
1:152357575:A:G	F71L	0.995
1:152358775:A:G	L37P	0.992
1:152357616:A:C	I57S	0.991
1:152357616:A:T	I57N	0.991
1:152358751:A:G	L45P	0.991
1:152357553:A:T	I78K	0.990
1:152357574:A:C	F71C	0.990
1:152357604:A:G	L61P	0.990
1:152358841:A:G	F15S	0.990
1:152358862:A:T	V8D	0.990
1:152357549:G:C	F79L	0.989
1:152357549:G:T	F79L	0.989
1:152357551:A:G	F79L	0.989
1:152357550:A:G	F79S	0.988
1:152358864:A:C	S7R	0.988
1:152358864:A:T	S7R	0.988

dbSNP variants (sampled 300 via entrez): RS1000153531 (1:152357218 A>G), RS1000312776 (1:152352531 G>C,T), RS1000690796 (1:152361453 A>G), RS1000757210 (1:152358788 G>A), RS1000774803 (1:152353016 G>A,T), RS1000895041 (1:152350974 T>C), RS1002057793 (1:152359776 C>T), RS1002429842 (1:152359416 G>A), RS1002887761 (1:152361513 C>G,T), RS1002995167 (1:152361116 T>C), RS1003026168 (1:152361437 G>A), RS1003267288 (1:152361921 T>C), RS1003467958 (1:152361895 T>A,C), RS1003593504 (1:152349848 C>T), RS1004306738 (1:152359718 T>C,G)

Disease associations

OMIM: gene MIM:616284 | disease phenotypes: MIM:618084

GenCC curated gene-disease

Disease	Classification	Inheritance
peeling skin syndrome 6	Strong	Autosomal recessive
peeling skin syndrome type A	Supportive	Autosomal recessive

Mondo (2): peeling skin syndrome 6 (MONDO:0054852), peeling skin syndrome type A (MONDO:0014555)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000958	Dry skin
HP:0000989	Pruritus
HP:0001036	Parakeratosis
HP:0001047	Atopic dermatitis
HP:0003577	Congenital onset
HP:0040162	Orthokeratosis
HP:0040189	Scaling skin

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001960_3	Eating disorders	2.000000e-06
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST007994_25	Asthma (age of onset)	8.000000e-27
GCST007995_26	Asthma (childhood onset)	2.000000e-65
GCST008916_75	Asthma	2.000000e-08
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST009798_76	Asthma	1.000000e-22
GCST011709_2	Systemic sclerosis	2.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724685 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
hydroquinone	increases expression	1
avobenzone	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Furaldehyde	affects cotreatment, affects localization, decreases expression, increases expression	1
Sodium Chloride	affects cotreatment, affects localization, increases expression, decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Volatile Organic Compounds	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697474	Binding	Inhibition of FLG2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.