FLG2

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

Basic information

Region (hg38): 1:152348734-152360006

Links

ENSG00000143520 ∙ NCBI:388698 ∙ OMIM:616284 ∙ HGNC:33276 ∙ Uniprot:Q5D862 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peeling skin syndrome 6 (Strong), mode of inheritance: AR
• peeling skin syndrome 6 (Limited), mode of inheritance: AR
• peeling skin syndrome 6 (Strong), mode of inheritance: AR
• peeling skin syndrome 6 (Strong), mode of inheritance: AR
• peeling skin syndrome type A (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peeling skin syndrome 6	AR	General	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	Dermatologic	28884927; 29505760; 29758285

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLG2 gene.

• Inborn genetic diseases (98 variants)
• not provided (34 variants)
• Peeling skin syndrome 6 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLG2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	6	15
missense			91	11	8	110
nonsense			1		1	2
start loss						0
frameshift		1	2			3
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					3	3
Total	0	1	94	20	19

Variants in FLG2

This is a list of pathogenic ClinVar variants found in the FLG2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-152350656-G-T			Benign (May 04, 2021)
1-152350700-C-T			Likely benign (Nov 01, 2023)
1-152350848-C-T		not specified	Uncertain significance (May 09, 2023)
1-152350951-C-T		not specified	Uncertain significance (Oct 17, 2023)
1-152350968-C-T		not specified	Uncertain significance (Feb 10, 2022)
1-152351107-C-T		not specified	Likely benign (Mar 23, 2023)
1-152351121-G-A		not specified	Uncertain significance (Jan 18, 2022)
1-152351139-T-A		not specified	Uncertain significance (Nov 28, 2023)
1-152351142-C-T			Likely benign (Jul 01, 2022)
1-152351153-T-C			Likely benign (Jul 01, 2022)
1-152351166-C-G		not specified	Uncertain significance (Mar 02, 2023)
1-152351169-G-A		not specified	Uncertain significance (Nov 09, 2021)
1-152351174-G-A			Likely benign (Jul 01, 2023)
1-152351271-G-T		not specified	Uncertain significance (Jun 16, 2023)
1-152351280-C-G		not specified	Uncertain significance (Mar 01, 2024)
1-152351331-C-A		not specified	Uncertain significance (Apr 27, 2022)
1-152351362-C-T			Uncertain significance (Feb 01, 2024)
1-152351437-C-A		not specified	Uncertain significance (Apr 17, 2023)
1-152351437-C-G		not specified	Uncertain significance (Jan 03, 2024)
1-152351526-T-C			Benign (Oct 01, 2023)
1-152351623-C-T			Benign (May 05, 2021)
1-152351643-C-T		not specified	Uncertain significance (May 27, 2022)
1-152351688-T-G		not specified	Likely benign (Apr 28, 2022)
1-152351718-G-A		not specified	Uncertain significance (Jan 31, 2024)
1-152351726-G-T			Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLG2	protein_coding	protein_coding	ENST00000388718	2	11272

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0180	0.506	125595	0	3	125598	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.19	1260	1.15e+3	1.10	0.0000552	15111
Missense in Polyphen		121	112.15	1.0789		1435
Synonymous	-3.04	523	442	1.18	0.0000225	4939
Loss of Function	-0.427	2	1.45	1.38	6.00e-8	21

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Intolerance Scores

• loftool: 0.982
• rvis_EVS: 2.28
• rvis_percentile_EVS: 98.27

Haploinsufficiency Scores

• pHI: 0.104
• hipred: N
• hipred_score: 0.112
• ghis: 0.433

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0380

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Flg2

Gene ontology

• Biological process: neutrophil degranulation;establishment of skin barrier
• Cellular component: cornified envelope;extracellular region;nucleus;cytoplasm;keratohyalin granule;tertiary granule lumen
• Molecular function: calcium ion binding;structural constituent of epidermis;transition metal ion binding