KRT16

keratin 16, the group of Keratins, type I

Basic information

Region (hg38): 17:41609777-41615899

Links

ENSG00000186832 ∙ NCBI:3868 ∙ OMIM:148067 ∙ HGNC:6423 ∙ Uniprot:P08779 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pachyonychia congenita 1 (Strong), mode of inheritance: AD
• palmoplantar keratoderma, nonepidermolytic, focal 1 (Strong), mode of inheritance: AD
• pachyonychia congenita 1 (Strong), mode of inheritance: AD
• palmoplantar keratoderma, nonepidermolytic, focal 1 (Moderate), mode of inheritance: AD
• pachyonychia congenita (Supportive), mode of inheritance: AD
• isolated focal non-epidermolytic palmoplantar keratoderma (Supportive), mode of inheritance: AD
• pachyonychia congenita 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Palmoplantar keratoderma, nonepidermolytic, focal 1; Pachyonychia congenita 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	7544664; 8595410; 10521820; 10839714; 11359398; 11886499; 20301457; 21160496; 21326300; 22098151; 22668561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT16 gene.

• not provided (85 variants)
• Inborn genetic diseases (15 variants)
• Pachyonychia congenita 1 (12 variants)
• Palmoplantar keratoderma, nonepidermolytic, focal 1 (6 variants)
• Pachyonychia congenita 1;Palmoplantar keratoderma, nonepidermolytic, focal 1 (4 variants)
• Palmoplantar keratoderma, nonepidermolytic, focal 1;Pachyonychia congenita 1 (3 variants)
• KRT16-related condition (1 variants)
• Epidermolytic palmoplantar keratoderma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT16 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				13	9	22
missense	6	4	24	10	8	52
nonsense			2	1		3
start loss						0
frameshift		1	1	1		3
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1	1	3	5
Total	7	5	28	26	20

Highest pathogenic variant AF is 0.00000657

Variants in KRT16

This is a list of pathogenic ClinVar variants found in the KRT16 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-41609984-A-G		Palmoplantar keratoderma, nonepidermolytic, focal 1	Uncertain significance (Feb 02, 2021)
17-41610000-G-A			Likely benign (Aug 27, 2023)
17-41610014-G-A			Benign (Nov 17, 2021)
17-41610044-AGAG-A			Likely benign (Aug 04, 2023)
17-41610193-C-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
17-41610195-C-T		Inborn genetic diseases	Uncertain significance (Nov 23, 2022)
17-41610220-C-T		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
17-41610252-A-G		Pachyonychia congenita 1 • Palmoplantar keratoderma, nonepidermolytic, focal 1	Benign (Jan 31, 2024)
17-41610332-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2022)
17-41610340-TC-T			not provided (-)
17-41610341-CGCCCTCCAGCAGGCGGCGGTAGGTGG-GCC		Palmoplantar keratoderma, nonepidermolytic, focal 1	Pathogenic (Jun 01, 2000)
17-41610356-G-A			Likely benign (Aug 04, 2023)
17-41610359-G-A		KRT16-related disorder	Benign (Jan 19, 2024)
17-41610443-G-A		KRT16-related disorder	Benign/Likely benign (Dec 25, 2023)
17-41610449-G-A			Uncertain significance (Jun 15, 2022)
17-41610494-A-C		Inborn genetic diseases	Likely benign (Mar 28, 2023)
17-41610514-C-T			Likely benign (Jul 20, 2020)
17-41610525-C-A			Uncertain significance (Mar 04, 2022)
17-41610545-A-G			Uncertain significance (May 08, 2023)
17-41610549-T-A		Pachyonychia congenita 1 • not specified	Conflicting classifications of pathogenicity (Jan 29, 2024)
17-41610556-A-C			Likely benign (Jan 24, 2023)
17-41610924-C-A			Benign (May 31, 2023)
17-41610924-C-T			Uncertain significance (Jun 02, 2017)
17-41610944-G-A			Likely benign (Jul 29, 2022)
17-41610987-A-G			Likely benign (May 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT16	protein_coding	protein_coding	ENST00000301653	8	6122

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-14	0.00697	125605	0	143	125748	0.000569

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.313	294	279	1.05	0.0000190	3060
Missense in Polyphen		63	75.768	0.83148		1059
Synonymous	-2.22	153	122	1.26	0.00000846	969
Loss of Function	-0.458	20	17.9	1.12	8.02e-7	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00532	0.00493
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000368	0.000316
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.000507	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Epidermis-specific type I keratin that plays a key role in skin. Acts as a regulator of innate immunity in response to skin barrier breach: required for some inflammatory checkpoint for the skin barrier maintenance. {ECO:0000250|UniProtKB:Q9Z2K1}.
• Disease: DISEASE: Pachyonychia congenita 1 (PC1) [MIM:167200]: An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma, follicular hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the hands and feet is usually present. {ECO:0000269|PubMed:10521820, ECO:0000269|PubMed:10606845, ECO:0000269|PubMed:10839714, ECO:0000269|PubMed:11359398, ECO:0000269|PubMed:11886499, ECO:0000269|PubMed:16250206, ECO:0000269|PubMed:17719747, ECO:0000269|PubMed:21160496, ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:22668561, ECO:0000269|PubMed:24118415, ECO:0000269|PubMed:7539673}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratoderma, palmoplantar, non-epidermolytic, focal 1 (FNEPPK1) [MIM:613000]: A dermatological disorder characterized by non-epidermolytic palmoplantar keratoderma limited to the pressure points on the balls of the feet, with later mild involvement on the palms. Oral, genital and follicular keratotic lesions are often present. {ECO:0000269|PubMed:8595410}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=KRT16 and KRT17 are coexpressed only in pathological situations such as metaplasias and carcinomas of the uterine cervix and in psoriasis vulgaris.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);Vitamin D Receptor Pathway;Keratinization;Developmental Biology (Consensus)

Recessive Scores

• pRec: 0.479

Intolerance Scores

• loftool: 0.120
• rvis_EVS: 0.64
• rvis_percentile_EVS: 84.1

Haploinsufficiency Scores

• pHI: 0.170
• hipred: N
• hipred_score: 0.297

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt16
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); digestive/alimentary 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; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: morphogenesis of an epithelium;inflammatory response;cytoskeleton organization;aging;cell population proliferation;epidermis development;keratinocyte differentiation;negative regulation of cell migration;keratinization;hair cycle;innate immune response;intermediate filament cytoskeleton organization;keratinocyte migration;establishment of skin barrier;cornification
• Cellular component: nucleus;cytosol;cytoskeleton;intermediate filament;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding