KRT10

keratin 10, the group of Keratins, type I

Basic information

Region (hg38): 17:40818116-40822614

Previous symbols: [ "KPP" ]

Links

ENSG00000186395 ∙ NCBI:3858 ∙ OMIM:148080 ∙ HGNC:6413 ∙ Uniprot:P13645 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermolytic ichthyosis (Strong), mode of inheritance: AD
• congenital reticular ichthyosiform erythroderma (Strong), mode of inheritance: AD
• annular epidermolytic ichthyosis (Strong), mode of inheritance: AD
• annular epidermolytic ichthyosis (Strong), mode of inheritance: AD
• congenital reticular ichthyosiform erythroderma (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Strong), mode of inheritance: AR
• epidermolytic ichthyosis (Supportive), mode of inheritance: AD
• annular epidermolytic ichthyosis (Supportive), mode of inheritance: AD
• congenital reticular ichthyosiform erythroderma (Supportive), mode of inheritance: AD
• autosomal recessive epidermolytic ichthyosis (Supportive), mode of inheritance: AR
• ichthyosis, annular epidermolytic 1 (Strong), mode of inheritance: AD
• epidermolytic ichthyosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Erythroderma, ichthyosiform, congenital reticular; Aaru disease; Ichthyosis, annular epidermolytic, 1; Epidermolytic hyperkeratosis 1; Epidermolytic hyperkeratosis 2; Ichthyosis with confetti	AD/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	1381287; 1380725; 7682695; 9036939; 19443303; 19474805; 19689541; 20302579; 20798280; 21271994; 21463361; 21929535; 22035476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT10 gene.

• not provided (113 variants)
• Inborn genetic diseases (13 variants)
• Bullous ichthyosiform erythroderma (6 variants)
• not specified (4 variants)
• Congenital reticular ichthyosiform erythroderma (4 variants)
• Annular epidermolytic ichthyosis (2 variants)
• KRT10-related condition (2 variants)
• Bullous ichthyosiform erythroderma;Congenital reticular ichthyosiform erythroderma;Annular epidermolytic ichthyosis (2 variants)
• Annular epidermolytic ichthyosis;Congenital reticular ichthyosiform erythroderma;Bullous ichthyosiform erythroderma (2 variants)
• Congenital reticular ichthyosiform erythroderma;Bullous ichthyosiform erythroderma;Annular epidermolytic ichthyosis (1 variants)
• Epidermolytic acanthoma (1 variants)
• Epidermolytic nevus (1 variants)
• Congenital reticular ichthyosiform erythroderma;Porcupine man;Ichthyosis, annular epidermolytic 1;Bullous ichthyosiform erythroderma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT10 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	9	18
missense	8	3	27	10	8	56
nonsense		1				1
start loss						0
frameshift					1	1
inframe indel			9	9	8	26
splice donor/acceptor (+/-2bp)	3	1				4
splice region			1			1
non coding				1	10	11
Total	11	5	36	29	36

Variants in KRT10

This is a list of pathogenic ClinVar variants found in the KRT10 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-40818360-T-C			Benign (Mar 03, 2015)
17-40818411-T-C			Benign (May 21, 2021)
17-40818434-G-A			Benign (May 13, 2021)
17-40818492-T-C		Porcupine man;Congenital reticular ichthyosiform erythroderma;Bullous ichthyosiform erythroderma;Ichthyosis, annular epidermolytic 1	Likely benign (Oct 11, 2022)
17-40818497-GA-G			Benign (Mar 08, 2023)
17-40818497-G-GA			Benign (Aug 03, 2023)
17-40818811-C-A			Benign (Jan 12, 2024)
17-40818832-G-A		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
17-40818847-CT-GG			Uncertain significance (Feb 08, 2023)
17-40818851-A-AGCT			Uncertain significance (Feb 13, 2023)
17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCT		not specified • Annular epidermolytic ichthyosis;Congenital reticular ichthyosiform erythroderma;Bullous ichthyosiform erythroderma • KRT10-related disorder	Benign/Likely benign (Jan 29, 2024)
17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCT		Congenital reticular ichthyosiform erythroderma;Annular epidermolytic ichthyosis;Bullous ichthyosiform erythroderma	Uncertain significance (Jan 28, 2022)
17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCT		not specified	Conflicting classifications of pathogenicity (Aug 04, 2023)
17-40818859-C-CCGCCGTATCCGCCGCCGGAGCTGCTGCCTG			Likely benign (Aug 14, 2023)
17-40818867-TCCGCCGCCGGAGCTGCTG-T			Uncertain significance (Nov 08, 2022)
17-40818878-A-AGCT		KRT10-related disorder	Benign/Likely benign (Nov 24, 2023)
17-40818880-C-CGCTGCCGCCGCCGTATCCGCCGCCGGAGCT			Benign (Mar 03, 2015)
17-40818881-T-TGCTGCCGCCGCCGGA		KRT10-related disorder	Benign/Likely benign (Dec 07, 2023)
17-40818891-GCCGGAGCTGCCGCCC-G		KRT10-related disorder	Benign (Aug 29, 2019)
17-40818895-G-T			Benign (Oct 24, 2022)
17-40818897-G-T			Benign/Likely benign (Oct 19, 2022)
17-40818899-T-C			Benign/Likely benign (Oct 19, 2022)
17-40818901-C-T			Uncertain significance (Feb 27, 2022)
17-40818903-G-T			Benign/Likely benign (Jan 24, 2024)
17-40818906-C-G			Likely benign (Oct 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT10	protein_coding	protein_coding	ENST00000269576	8	4479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00253	0.997	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.253	280	292	0.958	0.0000160	3704
Missense in Polyphen		94	118.62	0.79242		1548
Synonymous	-1.56	141	119	1.18	0.00000619	1210
Loss of Function	3.00	9	25.3	0.356	0.00000132	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.000163	0.000163
South Asian	0.000265	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the establishment of the epidermal barrier on plantar skin. {ECO:0000250|UniProtKB:P02535}.
• 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:10201536, ECO:0000269|PubMed:1380725, ECO:0000269|PubMed:1381287, ECO:0000269|PubMed:21271994, ECO:0000269|PubMed:7507150, ECO:0000269|PubMed:7507152, ECO:0000269|PubMed:7508181, ECO:0000269|PubMed:7512983, ECO:0000269|PubMed:7526210, ECO:0000269|Ref.7}. 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:9036939, ECO:0000269|PubMed:9856845}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Erythroderma, ichthyosiform, congenital reticular (CRIE) [MIM:609165]: A rare skin condition characterized by slowly enlarging islands of normal skin surrounded by erythematous ichthyotic patches in a reticulated pattern. The condition starts in infancy as a lamellar ichthyosis, with small islands of normal skin resembling confetti appearing in late childhood and at puberty. Histopathologic findings include band-like parakeratosis, psoriasiform acanthosis, and vacuolization of keratinocytes with binucleated cells in the upper epidermis, sometimes associated with amyloid deposition in the dermis. Ultrastructural abnormalities include perinuclear shells formed from a network of fine filaments in the upper epidermis. {ECO:0000269|PubMed:20798280}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Staphylococcus aureus infection - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Hair Follicle Development- Induction (Part 1 of 3);Keratinization;Developmental Biology (Consensus)

Recessive Scores

• pRec: 0.540

Intolerance Scores

• loftool: 0.0859
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.38

Haploinsufficiency Scores

• pHI: 0.541
• hipred: N
• hipred_score: 0.471
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.734

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt10
• 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; neoplasm; endocrine/exocrine gland phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; immune 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)

Gene ontology

• Biological process: peptide cross-linking;keratinocyte differentiation;keratinization;positive regulation of epidermis development;protein heterotetramerization;cornification
• Cellular component: cornified envelope;extracellular space;nucleus;cytoplasm;cytosol;intermediate filament;membrane;extracellular exosome
• Molecular function: structural constituent of epidermis;protein heterodimerization activity