GeneBe

KRT17

protein-coding

keratin 17, the group of Keratins, type I

Gene summary

This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. [provided by RefSeq, Aug 2008]

Previous symbols:
  • PCHC1

MANE transcript

NM_000422.3

Inheritance

AD

ClinVar variants

P:16U:80B:62

Top phenotype

Steatocystoma multiplex; Pachyonychia congenita 2

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr17:41,619,442-41,624,842

External References & Databases

Ensembl (ENSG00000128422)NCBI Gene (3872)OMIM (148069)HGNC:6427GenCCUniProt (Q04695)AlphaFoldClinVar (KRT17)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~5.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

sebocystomatosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008485

Submitter: PanelApp Australia

sebocystomatosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008485

Submitter: Labcorp Genetics (formerly Invitae)

sebocystomatosisDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008485

Submitter: G2P

pachyonychia congenita 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008174

Submitter: Genomics England PanelApp

pachyonychia congenita 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008174

Submitter: PanelApp Australia

sebocystomatosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008485

Submitter: Genomics England PanelApp

pachyonychia congenitaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016471

Submitter: Orphanet

pachyonychia congenita 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008174

Submitter: Labcorp Genetics (formerly Invitae)

sebocystomatosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008485

Submitter: Orphanet

Clinical Genomic Database (CGD)

Steatocystoma multiplex; Pachyonychia congenita 2AD

Manifestation: Dental; Dermatologic

Intervention: General

Rationale: 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

Refs: 7529318; 7539673; 9008238; 11886499; 20301457; 22264670Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT17 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 139
Inborn genetic diseasesTotal: 36
Pachyonychia congenita 2Total: 18
not specifiedTotal: 15
KRT17-related disorderTotal: 15
Steatocystoma multiplexTotal: 11
KRT17-related disordersTotal: 5
Nonsyndromic congenital nail disorder 4Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000422.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
27
clinvar
8
clinvar
 36
missense
11
clinvar
5
clinvar
75
clinvar
18
clinvar
8
clinvar
 117
nonsense
1
clinvar
1
clinvar
 2
start loss
1
clinvar
 1
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total115804616158

Highest pathogenic variant AF is 0.000026712183

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000422.3RefSeqNP_000413.18MANE Select
ENST00000311208.13EnsemblENSP00000308452.88MANE Select
ENST00000463128.5EnsemblENSP00000468672.13Standard
ENST00000577817.3EnsemblENSP00000467418.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Estrogen signaling pathway - Homo sapiens (human)
  • Keratinization
  • Developmental Biology
  • EGFR1
  • Glucocorticoid receptor regulatory network

Biological Process

  • cytoskeleton organization
  • signal transduction
  • epidermis development
  • hair follicle morphogenesis
  • keratinization

Molecular Function

  • structural constituent of cytoskeleton
  • protein binding
  • MHC class II receptor activity
  • MHC class II protein binding

Cellular Component

  • cytosol
  • intermediate filament
  • intermediate filament cytoskeleton
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000311208
Coding exons
8
Length
5406
Individuals with no LoFs
125612
Homozygous LoFs
0
Heterozygous LoFs
136
Defined
125748
p
0.000541
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.4922832611.090.00001872808
Missense (PolyPhen)6267.3230.92093892
Synonymous-1.191251091.140.00000710877
Loss of Function0.4011819.90.9030.00000106220

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.00110.0011notable
Ashkenazi Jewish0.000890.00089rare
East Asian0.000110.00011rare
Finnish0.000180.00018rare
European (Non-Finnish)0.000580.00058rare
South Asian0.000460.00046rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.228

Intolerance Scores

LoFtool
0.191
RVIS EVS
-0.24
RVIS percentile EVS
36.17

Essentials

Essential (CRISPR)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.931

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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