GeneBe

KRT16

keratin 16, the group of Keratins, type I

Basic information

Region (hg38): 17:41609778-41615899

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
  • pachyonychia congenita 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Palmoplantar keratoderma, nonepidermolytic, focal 1; Pachyonychia congenita 1ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic7544664; 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 (108 variants)
  • Inborn_genetic_diseases (38 variants)
  • Pachyonychia_congenita_1 (23 variants)
  • KRT16-related_disorder (15 variants)
  • Palmoplantar_keratoderma,_nonepidermolytic,_focal_1 (14 variants)
  • not_specified (2 variants)
  • EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
  • Palmoplantar_keratoderma,_epidermolytic (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. These statistics are base on transcript: NM_000005557.4. 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.

EffectPLPVUSLBBSum
synonymous
21
clinvar
8
clinvar
 29
missense
14
clinvar
4
clinvar
57
clinvar
18
clinvar
7
clinvar
 100
nonsense
4
clinvar
1
clinvar
 5
start loss
0
frameshift
1
clinvar
3
clinvar
1
clinvar
 5
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total 14 5 64 42 15

Highest pathogenic variant AF is 0.00000743476

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KRT16protein_codingprotein_codingENST00000301653 86122
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.50e-140.0069712560501431257480.000569
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.3132942791.050.00001903060
Missense in Polyphen6375.7680.831481059
Synonymous-2.221531221.260.00000846969
Loss of Function-0.4582017.91.128.02e-7213

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.005320.00493
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.0001390.000139
European (Non-Finnish)0.0003680.000316
Middle Eastern0.0001630.000163
South Asian0.00003270.0000327
Other0.0005070.000489

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
ghis

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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