GeneBe

KRT2

protein-coding

keratin 2, the group of Keratins, type II

Gene summary

The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is expressed largely in the upper spinous layer of epidermal keratinocytes and mutations in this gene have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

Previous symbols:
  • KRT2A

MANE transcript

NM_000423.3

Inheritance

AD

ClinVar variants

P:12U:120B:77

Top phenotype

Ichthyosis bullosa of Siemens; Ichthyosis exfoliativa

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr12:52,644,558-52,652,211

External References & Databases

Ensembl (ENSG00000172867)NCBI Gene (3849)OMIM (600194)HGNC:6439GenCCUniProt (P35908)AlphaFoldClinVar (KRT2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

superficial epidermolytic ichthyosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007813

Submitter: Ambry Genetics

superficial epidermolytic ichthyosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007813

Submitter: Orphanet

superficial epidermolytic ichthyosisDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007813

Submitter: G2P

superficial epidermolytic ichthyosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007813

Submitter: Labcorp Genetics (formerly Invitae)

superficial epidermolytic ichthyosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007813

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ichthyosis bullosa of Siemens; Ichthyosis exfoliativaAD

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: 2138447; 2004005; 8077693; 7524919; 7521372; 9833038; 10084318; 10233323; 10620137; 11167982; 15949009Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT2 variants in ClinVar

7 Conditions Cataloged
Inborn genetic diseasesTotal: 99
not providedTotal: 92
Ichthyosis bullosa of SiemensTotal: 61
KRT2-related disorderTotal: 22
not specifiedTotal: 17
Palmoplantar keratodermasTotal: 1
Exfoliative ichthyosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000423.3. 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
4
clinvar
21
clinvar
13
clinvar
 38
missense
6
clinvar
6
clinvar
116
clinvar
26
clinvar
14
clinvar
 168
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total661205027209

Highest pathogenic variant AF is 6.840666e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000423.3RefSeqNP_000414.29MANE Select
ENST00000309680.4EnsemblENSP00000310861.39MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Keratinization
  • Developmental Biology

Biological Process

  • keratinocyte development
  • epidermis development
  • peptide cross-linking
  • keratinization
  • keratinocyte activation

Molecular Function

  • structural constituent of cytoskeleton
  • protein binding
  • cytoskeletal protein binding
  • structural constituent of epidermis

Cellular Component

  • cornified envelope
  • extracellular space
  • nucleus
  • cytosol
  • intermediate filament

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000309680
Coding exons
9
Length
7607
Individuals with no LoFs
125723
Homozygous LoFs
0
Heterozygous LoFs
25
Defined
125748
p
0.0000994
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.7614003591.110.00002184105
Missense (PolyPhen)113117.380.962671543
Synonymous-2.771841421.300.000009051332
Loss of Function2.77923.40.3840.00000119306

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000140.00014rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.000150.00015rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Probably contributes to terminal cornification (PubMed:1380918). Associated with keratinocyte activation, proliferation and keratinization (PubMed:12598329). Plays a role in the establishment of the epidermal barrier on plantar skin (By similarity). {ECO:0000250|UniProtKB:Q3TTY5, ECO:0000269|PubMed:12598329, ECO:0000269|PubMed:1380918}.;
Disease
DISEASE: Ichthyosis bullosa of Siemens (IBS) [MIM:146800]: A rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints. {ECO:0000269|PubMed:10084318, ECO:0000269|PubMed:10233323, ECO:0000269|PubMed:10564334, ECO:0000269|PubMed:10620137, ECO:0000269|PubMed:10688369, ECO:0000269|PubMed:11167982, ECO:0000269|PubMed:11531804, ECO:0000269|PubMed:15949009, ECO:0000269|PubMed:7521371, ECO:0000269|PubMed:7524919, ECO:0000269|PubMed:8077693, ECO:0000269|PubMed:9036938, ECO:0000269|PubMed:9204966, ECO:0000269|PubMed:9804344, ECO:0000269|PubMed:9833038}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.110

Intolerance Scores

LoFtool
0.0905
RVIS EVS
0.29
RVIS percentile EVS
71.6

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.304

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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