KRT1

keratin 1, the group of Keratins, type II

Basic information

Region (hg38): 12:52674735-52680407

Previous symbols: [ "EHK1" ]

Links

ENSG00000167768 ∙ NCBI:3848 ∙ OMIM:139350 ∙ HGNC:6412 ∙ Uniprot:P04264 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diffuse nonepidermolytic palmoplantar keratoderma (Strong), mode of inheritance: AD
• ichthyosis hystrix of Curth-Macklin (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Strong), mode of inheritance: AD
• annular epidermolytic ichthyosis (Strong), mode of inheritance: AD
• annular epidermolytic ichthyosis (Strong), mode of inheritance: AD
• ichthyosis hystrix of Curth-Macklin (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Supportive), mode of inheritance: AD
• striate palmoplantar keratoderma (Supportive), mode of inheritance: AD
• ichthyosis hystrix of Curth-Macklin (Supportive), mode of inheritance: AD
• annular epidermolytic ichthyosis (Supportive), mode of inheritance: AD
• congenital reticular ichthyosiform erythroderma (Supportive), mode of inheritance: AD
• diffuse nonepidermolytic palmoplantar keratoderma (Supportive), mode of inheritance: AD
• epidermolytic ichthyosis (Moderate), mode of inheritance: AD
• ichthyosis, annular epidermolytic 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keratosis palmoplantaris striata III; Ichthyosis, cyclic, with epidermolytic hyperkeratosis; Ichthyosis, annular epidermolytic, 2; Ichthyosis histrix, Curth-Macklin type; Palmoplantar keratoderma, epidermolytic 2; Palmoplantar keratoderma, nonepidermolytic; Epidermolytic hyperkeratosis 1	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	14349943; 1381288; 1380725; 7682695; 7528239; 7512983; 10053007; 11286630; 11286616; 12406346; 11982762; 12648226; 16361731; 16417221; 16439967; 16487115; 16677804; 17255957; 18795921; 19470048; 21271994; 21496707; 22250628; 22834809; 30152556

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT1 gene.

• not provided (119 variants)
• Bullous ichthyosiform erythroderma (44 variants)
• Diffuse nonepidermolytic palmoplantar keratoderma (41 variants)
• Inborn genetic diseases (18 variants)
• KRT1-related condition (4 variants)
• not specified (3 variants)
• Annular epidermolytic ichthyosis (3 variants)
• Palmoplantar keratoderma, epidermolytic, 2 (2 variants)
• Ichthyosis, annular epidermolytic, 2 (2 variants)
• Epidermolytic hyperkeratosis 1 (2 variants)
• Abnormality of the skin (1 variants)
• Ichthyosis (1 variants)
• Hereditary angioedema with normal C1Inh (1 variants)
• 6 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT1 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	11	8	21
missense	7	14	45	7	7	80
nonsense						0
start loss						0
frameshift		1	2			3
inframe indel			4		3	7
splice donor/acceptor (+/-2bp)	3	2	1			6
splice region				1	2	3
non coding			3	2	12	17
Total	10	17	57	20	30

Variants in KRT1

This is a list of pathogenic ClinVar variants found in the KRT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-52674821-C-T		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma	Uncertain significance (Jan 12, 2018)
12-52674849-G-A		Diffuse nonepidermolytic palmoplantar keratoderma • Bullous ichthyosiform erythroderma	Benign (Jan 13, 2018)
12-52674918-C-T		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma	Uncertain significance (Jan 12, 2018)
12-52674996-A-C		Hereditary angioedema with normal C1Inh	not provided (Feb 01, 2020)
12-52675098-C-T		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma	Benign (Jan 12, 2018)
12-52675102-A-G		Diffuse nonepidermolytic palmoplantar keratoderma • Bullous ichthyosiform erythroderma	Benign (Jan 13, 2018)
12-52675121-C-A		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma	Uncertain significance (Jan 12, 2018)
12-52675216-T-A		Epidermolytic hyperkeratosis 1	Uncertain significance (Sep 22, 2023)
12-52675216-T-C		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 12, 2021)
12-52675230-T-C		Bullous ichthyosiform erythroderma • Diffuse nonepidermolytic palmoplantar keratoderma	Benign (Jan 29, 2024)
12-52675234-C-T		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
12-52675262-ACC-A			Uncertain significance (Jan 13, 2024)
12-52675262-A-AC		Congenital reticular ichthyosiform erythroderma	Pathogenic (Mar 16, 2015)
12-52675267-C-CA		Ichthyosis hystrix of Curth-Macklin	Pathogenic (Nov 30, 2023)
12-52675275-G-A		Inborn genetic diseases	Uncertain significance (Nov 29, 2021)
12-52675277-T-A			Likely benign (Dec 03, 2018)
12-52675281-C-T		Ichthyosis, annular epidermolytic 1	Uncertain significance (Sep 22, 2020)
12-52675282-G-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
12-52675282-GGCCTCCTATGGAGCCTCCAGAGCTCCCGCCGCCAGAGCCCCGGCCGCCAGAGCT-G			Uncertain significance (May 09, 2023)
12-52675304-G-C		KRT1-related disorder	Uncertain significance (Dec 22, 2023)
12-52675312-C-T			Uncertain significance (Nov 15, 2021)
12-52675330-C-A		Inborn genetic diseases	Uncertain significance (Aug 11, 2022)
12-52675339-C-T			Uncertain significance (May 09, 2023)
12-52675340-GCCGCCGCC-G			Likely pathogenic (Aug 01, 2018)
12-52675346-G-A		KRT1-related disorder	Likely benign (Sep 19, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT1	protein_coding	protein_coding	ENST00000252244	9	5672

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.736	0.264	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.252	349	363	0.963	0.0000222	4178
Missense in Polyphen		96	118.95	0.80708		1589
Synonymous	0.0494	142	143	0.995	0.00000929	1333
Loss of Function	3.85	5	26.3	0.190	0.00000156	288

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK. {ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:21544310}.
• Disease: DISEASE: Epidermolytic hyperkeratosis (EHK) [MIM:113800]: An autosomal dominant skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. {ECO:0000269|PubMed:10232403, ECO:0000269|PubMed:10688370, ECO:0000269|PubMed:10844506, ECO:0000269|PubMed:11531804, ECO:0000269|PubMed:12406348, ECO:0000269|PubMed:1380725, ECO:0000269|PubMed:1381288, ECO:0000269|PubMed:21271994, ECO:0000269|PubMed:7507151, ECO:0000269|PubMed:7507152, ECO:0000269|PubMed:7512983, ECO:0000269|PubMed:9856846}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ichthyosis hystrix, Curth-Macklin type (IHCM) [MIM:146590]: A genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmoplantar keratoderma and keratoses on the lips, ears, nipples and buttocks. {ECO:0000269|PubMed:11286616}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratoderma, palmoplantar, non-epidermolytic (NEPPK) [MIM:600962]: A dermatological disorder characterized by well- demarcated hyperkeratosis is present over the palms and soles. A red band is frequently present at the periphery of the keratosis. It is usually non-transgredient, with a sharp demarcation of the lesions at the wrists. {ECO:0000269|PubMed:11286630, ECO:0000269|PubMed:7528239}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ichthyosis annular epidermolytic (AEI) [MIM:607602]: A skin disorder resembling bullous congenital ichthyosiform erythroderma. Affected individuals present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. The feature that distinguishes AEI from BCIE is dramatic episodes of flares of annular polycyclic plaques with scale, which coalesce to involve most of the body surface and can persist for several weeks or even months. {ECO:0000269|PubMed:10053007, ECO:0000269|PubMed:10597140}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratoderma, palmoplantar, striate 3 (SPPK3) [MIM:607654]: A dermatological disorder characterized by thickening of the stratum corneum and epidermal layers on palms and soles. There is no involvement of non-palmoplantar skin, and both hair and nails are normal. {ECO:0000269|PubMed:11982762}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Corticotropin-releasing hormone signaling pathway;Keratinization;Developmental Biology;Neutrophil degranulation;Innate Immune System;Immune System;Regulation of nuclear beta catenin signaling and target gene transcription (Consensus)

Recessive Scores

• pRec: 0.610

Intolerance Scores

• loftool: 0.0564
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.68

Haploinsufficiency Scores

• pHI: 0.799
• hipred: Y
• hipred_score: 0.537
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.509

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt1
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; homeostasis/metabolism 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)

Gene ontology

• Biological process: complement activation, lectin pathway;retina homeostasis;response to oxidative stress;peptide cross-linking;keratinization;fibrinolysis;neutrophil degranulation;regulation of angiogenesis;negative regulation of inflammatory response;protein heterotetramerization;establishment of skin barrier;cornification
• Cellular component: cornified envelope;extracellular region;extracellular space;nucleus;cytosol;cytoskeleton;membrane;keratin filament;collagen-containing extracellular matrix;extracellular exosome;blood microparticle;ficolin-1-rich granule lumen
• Molecular function: protein binding;carbohydrate binding;structural constituent of epidermis;signaling receptor activity;protein heterodimerization activity