KRT2

keratin 2, the group of Keratins, type II

Basic information

Region (hg38): 12:52644557-52652211

Previous symbols: [ "KRT2A" ]

Links

ENSG00000172867 ∙ NCBI:3849 ∙ OMIM:600194 ∙ HGNC:6439 ∙ Uniprot:P35908 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• superficial epidermolytic ichthyosis (Strong), mode of inheritance: AD
• superficial epidermolytic ichthyosis (Strong), mode of inheritance: AD
• superficial epidermolytic ichthyosis (Strong), mode of inheritance: AD
• superficial epidermolytic ichthyosis (Supportive), mode of inheritance: AD
• superficial epidermolytic ichthyosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis bullosa of Siemens; Ichthyosis exfoliativa	AD	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	2138447; 2004005; 8077693; 7524919; 7521372; 9833038; 10084318; 10233323; 10620137; 11167982; 15949009

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT2 gene.

• Ichthyosis bullosa of Siemens (73 variants)
• not provided (68 variants)
• Inborn genetic diseases (25 variants)
• not specified (1 variants)
• Exfoliative ichthyosis (1 variants)
• KRT2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT2 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			2	8	15	25
missense	2	1	35	8	15	61
nonsense						0
start loss						0
frameshift				1		1
inframe indel			2		2	4
splice donor/acceptor (+/-2bp)						0
splice region			1		4	5
non coding			11	2	19	32
Total	2	1	50	19	51

Variants in KRT2

This is a list of pathogenic ClinVar variants found in the KRT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-52644572-G-A		Ichthyosis bullosa of Siemens	Benign (Jan 13, 2018)
12-52644581-T-C		Ichthyosis bullosa of Siemens	Uncertain significance (Feb 02, 2018)
12-52644608-G-A		Ichthyosis bullosa of Siemens	Benign (Jan 13, 2018)
12-52644665-G-A		Ichthyosis bullosa of Siemens	Benign (Jan 13, 2018)
12-52644673-T-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 13, 2018)
12-52644684-T-C		Ichthyosis bullosa of Siemens	Benign (Jan 12, 2018)
12-52644695-G-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)
12-52644697-C-G		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)
12-52644717-A-G		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)
12-52644718-C-T		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 13, 2018)
12-52644719-A-G		Ichthyosis bullosa of Siemens	Benign (Jan 12, 2018)
12-52644730-G-T		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 13, 2018)
12-52644740-A-G		Ichthyosis bullosa of Siemens	Benign (Jan 12, 2018)
12-52644756-G-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)
12-52644771-G-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 13, 2018)
12-52644803-C-T		Ichthyosis bullosa of Siemens	Likely benign (Jan 13, 2018)
12-52644804-G-A		Ichthyosis bullosa of Siemens	Benign (Jan 12, 2018)
12-52644894-A-C		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 13, 2018)
12-52644977-A-G		Ichthyosis bullosa of Siemens	Benign (Jan 12, 2018)
12-52645027-A-G			Uncertain significance (Sep 09, 2020)
12-52645034-G-T			Likely benign (Mar 12, 2022)
12-52645039-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 17, 2023)
12-52645066-T-C		Inborn genetic diseases	Likely benign (Jan 16, 2024)
12-52645070-C-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)
12-52645110-C-A		Ichthyosis bullosa of Siemens	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT2	protein_coding	protein_coding	ENST00000309680	9	7607

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00129	0.997	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.761	400	359	1.11	0.0000218	4105
Missense in Polyphen		113	117.38	0.96267		1543
Synonymous	-2.77	184	142	1.30	0.00000905	1332
Loss of Function	2.77	9	23.4	0.384	0.00000119	306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably contributes to terminal cornification (PubMed:1380918). Associated with keratinocyte activation, proliferation and keratinization (PubMed:12598329). Plays a role in the establishment of the epidermal barrier on plantar skin (By similarity). {ECO:0000250|UniProtKB:Q3TTY5, ECO:0000269|PubMed:12598329, ECO:0000269|PubMed:1380918}.
• Disease: DISEASE: Ichthyosis bullosa of Siemens (IBS) [MIM:146800]: A rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints. {ECO:0000269|PubMed:10084318, ECO:0000269|PubMed:10233323, ECO:0000269|PubMed:10564334, ECO:0000269|PubMed:10620137, ECO:0000269|PubMed:10688369, ECO:0000269|PubMed:11167982, ECO:0000269|PubMed:11531804, ECO:0000269|PubMed:15949009, ECO:0000269|PubMed:7521371, ECO:0000269|PubMed:7524919, ECO:0000269|PubMed:8077693, ECO:0000269|PubMed:9036938, ECO:0000269|PubMed:9204966, ECO:0000269|PubMed:9804344, ECO:0000269|PubMed:9833038}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Keratinization;Developmental Biology (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.0905
• rvis_EVS: 0.29
• rvis_percentile_EVS: 71.6

Haploinsufficiency Scores

• pHI: 0.158
• hipred: N
• hipred_score: 0.422
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.304

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Krt2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial 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); growth/size/body region phenotype; immune system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); pigmentation phenotype

Gene ontology

• Biological process: keratinocyte development;epidermis development;peptide cross-linking;keratinization;keratinocyte activation;keratinocyte proliferation;intermediate filament organization;positive regulation of epidermis development;keratinocyte migration;cornification
• Cellular component: cornified envelope;extracellular space;nucleus;cytosol;intermediate filament;membrane;keratin filament;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding;cytoskeletal protein binding;structural constituent of epidermis