FERMT1

FERM domain containing kindlin 1, the group of Fermitins|Pleckstrin homology domain containing|FERM domain containing

Basic information

Region (hg38): 20:6074844-6123214

Previous symbols: [ "C20orf42" ]

Links

ENSG00000101311 ∙ NCBI:55612 ∙ OMIM:607900 ∙ HGNC:15889 ∙ Uniprot:Q9BQL6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Kindler syndrome (Strong), mode of inheritance: AR
• Kindler syndrome (Strong), mode of inheritance: AR
• Kindler syndrome (Definitive), mode of inheritance: AR
• Kindler syndrome (Strong), mode of inheritance: AR
• Kindler syndrome (Supportive), mode of inheritance: AR
• Kindler syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kindler syndrome	AR	Dermatologic; Oncologic	Individuals have an increased risk of squamous cell carcinoma and surveillance for premalignant keratoses/early malignancy may allow early diagnosis and treatment	Dermatologic; Oncologic	13149722; 8910840; 9301588; 10809978; 12472544; 12668616; 12789646; 17460733; 17854379; 17916195; 17989907; 18410424; 18835760; 19292718; 19945624; 21336475; 21936020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FERMT1 gene.

• not provided (358 variants)
• Kindler syndrome (166 variants)
• Inborn genetic diseases (20 variants)
• not specified (18 variants)
• Abnormality of the skin (1 variants)
• FERMT1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FERMT1 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			5	50	14	69
missense	1		134	3	9	147
nonsense	11	1				12
start loss						0
frameshift	7	1				8
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	3	4				7
splice region	1		11	7	4	23
non coding			54	36	82	172
Total	23	6	194	89	105

Highest pathogenic variant AF is 0.000118

Variants in FERMT1

This is a list of pathogenic ClinVar variants found in the FERMT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-6074879-A-C		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6074923-G-A		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6074946-G-A		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6074952-T-C		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6074969-A-G		Kindler syndrome	Likely benign (Jan 12, 2018)
20-6075045-G-GT		Kindler syndrome	Uncertain significance (Jun 14, 2016)
20-6075047-TTG-T		Kindler syndrome	Uncertain significance (Jun 14, 2016)
20-6075048-TG-T		Kindler syndrome	Uncertain significance (Jun 14, 2016)
20-6075049-G-T		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075049-G-GT		Kindler syndrome	Uncertain significance (Jun 14, 2016)
20-6075055-T-C		Kindler syndrome	Likely benign (Jan 13, 2018)
20-6075064-TG-T		Kindler syndrome	Uncertain significance (Jun 14, 2016)
20-6075100-T-A		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075104-A-G		Kindler syndrome	Benign (Jan 13, 2018)
20-6075105-T-C		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075115-G-A		Kindler syndrome	Benign (Jan 12, 2018)
20-6075157-A-T		Kindler syndrome	Benign (Jan 13, 2018)
20-6075288-C-T		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075330-G-T		Kindler syndrome	Uncertain significance (Jan 15, 2018)
20-6075395-T-TA		Kindler syndrome	Benign (Jun 14, 2016)
20-6075399-C-T		Kindler syndrome	Uncertain significance (Jan 12, 2018)
20-6075642-C-T		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075701-C-T		Kindler syndrome	Uncertain significance (Jan 13, 2018)
20-6075709-G-A		Kindler syndrome	Benign (Jan 13, 2018)
20-6075715-G-A		Kindler syndrome	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FERMT1	protein_coding	protein_coding	ENST00000217289	14	48700

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.92e-11	0.974	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.780	322	364	0.885	0.0000205	4474
Missense in Polyphen		101	130.73	0.77259		1683
Synonymous	0.507	133	141	0.946	0.00000870	1238
Loss of Function	2.28	23	38.2	0.602	0.00000192	444

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000843	0.000843
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000163	0.000163
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000352	0.000325
Middle Eastern	0.000163	0.000163
South Asian	0.000392	0.000392
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites. May mediate TGF-beta 1 signaling in tumor progression. {ECO:0000269|PubMed:14634021, ECO:0000269|PubMed:17012746, ECO:0000269|PubMed:19804783}.
• Disease: DISEASE: Kindler syndrome (KNDLRS) [MIM:173650]: An autosomal recessive skin disorder characterized by skin blistering, photosensitivity, progressive poikiloderma, and extensive skin atrophy. Additional clinical features include gingival erosions, ocular, esophageal, gastrointestinal and urogenital involvement, and an increased risk of mucocutaneous malignancy. {ECO:0000269|PubMed:12668616, ECO:0000269|PubMed:12789646, ECO:0000269|PubMed:21936020}. Note=The disease is caused by mutations affecting the gene represented in this entry. Although most FERMT1 mutations are predicted to lead to premature termination of translation, and to loss of FERMT1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications (PubMed:21936020). {ECO:0000269|PubMed:21936020}.

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.471
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.79

Haploinsufficiency Scores

• pHI: 0.0751
• hipred: N
• hipred_score: 0.443
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.217

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fermt1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: fermt1
• Affected structure: median fin
• Phenotype tag: abnormal
• Phenotype quality: ruffled

Gene ontology

• Biological process: positive regulation of cell-matrix adhesion;cell adhesion;integrin-mediated signaling pathway;negative regulation of gene expression;positive regulation of transforming growth factor beta receptor signaling pathway;positive regulation of cell adhesion mediated by integrin;negative regulation of protein import into nucleus;keratinocyte proliferation;keratinocyte migration;negative regulation of timing of anagen;basement membrane organization;negative regulation of canonical Wnt signaling pathway;establishment of epithelial cell polarity;negative regulation of stem cell proliferation;positive regulation of transforming growth factor-beta secretion
• Cellular component: cytosol;cytoskeleton;focal adhesion;cell junction;ruffle membrane
• Molecular function: actin filament binding