GeneBe

KRT17

keratin 17, the group of Keratins, type I

Basic information

Region (hg38): 17:41619442-41624842

Previous symbols: [ "PCHC1" ]

Links

ENSG00000128422 ∙ NCBI:3872 ∙ OMIM:148069 ∙ HGNC:6427 ∙ Uniprot:Q04695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • pachyonychia congenita 2 (Strong), mode of inheritance: AD
  • sebocystomatosis (Strong), mode of inheritance: AD
  • sebocystomatosis (Strong), mode of inheritance: AD
  • pachyonychia congenita 2 (Strong), mode of inheritance: AD
  • pachyonychia congenita (Supportive), mode of inheritance: AD
  • sebocystomatosis (Supportive), mode of inheritance: AD
  • sebocystomatosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Steatocystoma multiplex; Pachyonychia congenita 2ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental; Dermatologic7529318; 7539673; 9008238; 11886499; 20301457; 22264670

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT17 gene.

  • not_provided (115 variants)
  • Inborn_genetic_diseases (32 variants)
  • Pachyonychia_congenita_2 (18 variants)
  • Steatocystoma_multiplex (11 variants)
  • KRT17-related_disorder (11 variants)
  • not_specified (1 variants)
  • Anonychia (1 variants)
  • Abnormality_of_the_skin (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT17 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000422.3. 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
1
clinvar
14
clinvar
12
clinvar
 27
missense
12
clinvar
2
clinvar
63
clinvar
15
clinvar
8
clinvar
 100
nonsense
1
clinvar
1
clinvar
 2
start loss
1
 1
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total 12 2 67 30 20

Highest pathogenic variant AF is 0.0000124039

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KRT17protein_codingprotein_codingENST00000311208 85406
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.10e-110.088412561201361257480.000541
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4922832611.090.00001872808
Missense in Polyphen6267.3230.92093892
Synonymous-1.191251091.140.00000710877
Loss of Function0.4011819.90.9030.00000106220

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001250.00125
Ashkenazi Jewish0.0008930.000893
East Asian0.0001100.000109
Finnish0.0001850.000185
European (Non-Finnish)0.0005850.000580
Middle Eastern0.0001100.000109
South Asian0.0004580.000457
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state (By similarity). Modulates the function of TNF-alpha in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway (By similarity). Involved in tissue repair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial "stem cells". Acts as a promoter of epithelial proliferation by acting a regulator of immune response in skin: promotes Th1/Th17-dominated immune environment contributing to the development of basaloid skin tumors (By similarity). May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation. {ECO:0000250|UniProtKB:Q9QWL7, ECO:0000269|PubMed:10844551, ECO:0000269|PubMed:15795121, ECO:0000269|PubMed:16713453}.;
Disease
DISEASE: Pachyonychia congenita 2 (PC2) [MIM:167210]: An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma and hyperhidrosis, follicular hyperkeratosis, multiple epidermal cysts, absent/sparse eyebrow and body hair, and by the presence of natal teeth. {ECO:0000269|PubMed:10571744, ECO:0000269|PubMed:11348474, ECO:0000269|PubMed:11874497, ECO:0000269|PubMed:11886499, ECO:0000269|PubMed:15102078, ECO:0000269|PubMed:15795125, ECO:0000269|PubMed:16250206, ECO:0000269|PubMed:16620218, ECO:0000269|PubMed:16625196, ECO:0000269|PubMed:17719747, ECO:0000269|PubMed:18547302, ECO:0000269|PubMed:19470054, ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:23278621, ECO:0000269|PubMed:23855588, ECO:0000269|PubMed:7539673, ECO:0000269|PubMed:9008238, ECO:0000269|PubMed:9767294}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Steatocystoma multiplex (SM) [MIM:184500]: Disease characterized by round or oval cystic tumors widely distributed on the back, anterior trunk, arms, scrotum, and thighs. {ECO:0000269|PubMed:16620218, ECO:0000269|PubMed:9008238, ECO:0000269|PubMed:9767294}. 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);Keratinization;Developmental Biology;EGFR1;Glucocorticoid receptor regulatory network (Consensus)

Recessive Scores

pRec
0.228

Intolerance Scores

loftool
0.191
rvis_EVS
-0.24
rvis_percentile_EVS
36.17

Haploinsufficiency Scores

pHI
hipred
N
hipred_score
0.397
ghis
0.456

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.931

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Krt17
Phenotype
digestive/alimentary phenotype; pigmentation 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); cellular phenotype; craniofacial 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
cytoskeleton organization;signal transduction;epidermis development;hair follicle morphogenesis;keratinization;cornification
Cellular component
cytosol;intermediate filament;intermediate filament cytoskeleton;extracellular exosome
Molecular function
structural constituent of cytoskeleton;protein binding;MHC class II receptor activity;MHC class II protein binding