KRT13

protein-coding

keratin 13, 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. This type I cytokeratin is paired with keratin 4 and expressed in the suprabasal layers of non-cornified stratified epithelia. Mutations in this gene and keratin 4 have been associated with the autosomal dominant disorder White Sponge Nevus. The type I cytokeratins are clustered in a region of chromosome 17q21.2. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_153490.3

Inheritance

ClinVar variants

P:2U:75B:45

Top phenotype

White sponge nevus 2

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr17:41,500,981-41,505,705

External References & Databases

Ensembl (ENSG00000171401)

Transcript & Mutation Effects

hg38 • Region Span ~4.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

white sponge nevus 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014346

Submitter: Ambry Genetics

white sponge nevus 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014346

Submitter: PanelApp Australia

hereditary mucosal leukokeratosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015748

Submitter: Orphanet

white sponge nevus 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014346

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

White sponge nevus 2AD

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: 7493031

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT13 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 70

White sponge nevus 2Total: 42

not providedTotal: 26

KRT13-related disorderTotal: 13

not specifiedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153490.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	10 clinvar	5 clinvar	19
missense	2 clinvar		70 clinvar	11 clinvar	17 clinvar	100
nonsense				1 clinvar		1
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	75	22	23	122

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153490.3	RefSeq	NP_705694.3	8	MANE Select
ENST00000246635.8	Ensembl	ENSP00000246635.3	8	MANE Select
NM_002274.4	RefSeq	NP_002265.3	7	Standard
ENST00000336861.7	Ensembl	ENSP00000336604.3	7	Standard

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

cytoskeleton organization
keratinization
cornification

Molecular Function

structural molecule activity
protein binding

Cellular Component

nucleus
cytosol
keratin filament
intermediate filament cytoskeleton
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246635
Coding exons: 8
Length: 4725
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.516	303	279	1.09	0.0000190	2962
Missense (PolyPhen)		129	116.23	1.1098		1367
Synonymous	-0.938	124	111	1.11	0.00000755	945
Loss of Function	2.06	8	17.2	0.465	7.55e-7	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: White sponge nevus 2 (WSN2) [MIM:615785]: A rare disorder characterized by the presence of soft, white, and spongy plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. {ECO:0000269|PubMed:10561721, ECO:0000269|PubMed:11379896, ECO:0000269|PubMed:14600690, ECO:0000269|PubMed:7493031}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.0615
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: 0.936

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium