KRT1
keratin 1, the group of Keratins, type II
Basic information
Region (hg38): 12:52674736-52680407
Previous symbols: [ "EHK1" ]
Links
Phenotypes
GenCC
Source:
- 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
- annular epidermolytic ichthyosis (Definitive), mode of inheritance: AD
- ichthyosis hystrix of Curth-Macklin (Definitive), mode of inheritance: AD
- ichthyosis, annular epidermolytic, 2 (Strong), mode of inheritance: AD
- autosomal recessive congenital ichthyosis 11 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- not_provided (148 variants)
- Inborn_genetic_diseases (64 variants)
- Epidermolytic_ichthyosis (38 variants)
- Diffuse_nonepidermolytic_palmoplantar_keratoderma (34 variants)
- KRT1-related_disorder (22 variants)
- Epidermolytic_hyperkeratosis_1 (6 variants)
- Ichthyosis_hystrix_of_Curth-Macklin (5 variants)
- Annular_epidermolytic_ichthyosis (4 variants)
- Palmoplantar_keratoderma,_epidermolytic,_2 (3 variants)
- Ichthyosis,_annular_epidermolytic,_2 (3 variants)
- not_specified (3 variants)
- Keratosis_palmoplantaris_striata_3 (2 variants)
- Ichthyosis,_annular_epidermolytic_1 (1 variants)
- Abnormality_of_the_skin (1 variants)
- Ichthyosis (1 variants)
- Prostate_cancer (1 variants)
- Palmoplantar_keratoderma,_epidermolytic (1 variants)
- Congenital_reticular_ichthyosiform_erythroderma (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. These statistics are base on transcript: NM_000006121.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 22 | 30 | ||||
| missense | 16 | 15 | 125 | 11 | 171 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 12 | |||||
| splice donor/acceptor (+/-2bp) | 8 | |||||
| Total | 27 | 19 | 133 | 33 | 9 |
Highest pathogenic variant AF is 0.00000205213
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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