GeneBe

KRT16

protein-coding

keratin 16, the group of Keratins, type I

Gene summary

The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region of chromosome 17q12-q21. This keratin has been coexpressed with keratin 14 in a number of epithelial tissues, including esophagus, tongue, and hair follicles. Mutations in this gene are associated with type 1 pachyonychia congenita, non-epidermolytic palmoplantar keratoderma and unilateral palmoplantar verrucous nevus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005557.4

Inheritance

AD

ClinVar variants

P:19U:77B:67

Top phenotype

Palmoplantar keratoderma, nonepidermolytic, focal 1; Pachyonychia congenita 1

gnomAD constraint

pLI —, LoF o/e 1.12

Max pathogenic AF

—

Genomic locus

chr17:41,609,778-41,615,899

External References & Databases

Ensembl (ENSG00000186832)NCBI Gene (3868)OMIM (148067)HGNC:6423GenCCUniProt (P08779)AlphaFoldClinVar (KRT16)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pachyonychia congenita 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008173

Submitter: Ambry Genetics

isolated focal non-epidermolytic palmoplantar keratodermaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014622

Submitter: Orphanet

pachyonychia congenita 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008173

Submitter: Ambry Genetics

pachyonychia congenita 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008173

Submitter: Genomics England PanelApp

pachyonychia congenita 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008173

Submitter: Labcorp Genetics (formerly Invitae)

palmoplantar keratoderma, nonepidermolytic, focal 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013073

Submitter: PanelApp Australia

palmoplantar keratoderma, nonepidermolytic, focal 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013073

Submitter: Ambry Genetics

palmoplantar keratoderma, nonepidermolytic, focal 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013073

Submitter: Genomics England PanelApp

pachyonychia congenitaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016471

Submitter: Orphanet

pachyonychia congenita 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008173

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Palmoplantar keratoderma, nonepidermolytic, focal 1; Pachyonychia congenita 1AD

Manifestation: 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: 7544664; 8595410; 10521820; 10839714; 11359398; 11886499; 20301457; 21160496; 21326300; 22098151; 22668561Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT16 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 130
Inborn genetic diseasesTotal: 43
Pachyonychia congenita 1Total: 23
KRT16-related disorderTotal: 17
Palmoplantar keratoderma, nonepidermolytic, focal 1Total: 15
not specifiedTotal: 14
EBV-positive nodal T- and NK-cell lymphomaTotal: 1
Palmoplantar keratoderma, epidermolyticTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005557.4. 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
26
clinvar
6
clinvar
 32
missense
13
clinvar
4
clinvar
70
clinvar
25
clinvar
6
clinvar
 118
nonsense
4
clinvar
2
clinvar
 6
start loss
0
frameshift
2
clinvar
3
clinvar
1
clinvar
 6
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total136775512163

Highest pathogenic variant AF is 0.00000743476

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005557.4RefSeqNP_005548.28MANE Select
ENST00000301653.9EnsemblENSP00000301653.38MANE Select
ENST00000590990.1EnsemblENSP00000467105.11Standard
ENST00000593067.1EnsemblENSP00000467124.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Estrogen signaling pathway - Homo sapiens (human)
  • Vitamin D Receptor Pathway
  • Keratinization
  • Developmental Biology

Biological Process

  • morphogenesis of an epithelium
  • inflammatory response
  • cytoskeleton organization
  • aging
  • cell population proliferation

Molecular Function

  • structural constituent of cytoskeleton
  • protein binding

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000301653
Coding exons
8
Length
6122
Individuals with no LoFs
125605
Homozygous LoFs
0
Heterozygous LoFs
143
Defined
125748
p
0.000569
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3132942791.050.00001903060
Missense (PolyPhen)6375.7680.831481059
Synonymous-2.221531221.260.00000846969
Loss of Function-0.4582017.91.128.02e-7213

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00430.0039notable
Latino/Admixed American0.000980.00095rare
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000370.00032rare
South Asian0.0000330.000033rare
Other0.000510.00049rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.479

Intolerance Scores

LoFtool
0.120
RVIS EVS
0.64
RVIS percentile EVS
84.1

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.584

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.