KRT6C

protein-coding

keratin 6C, the group of Keratins, type II

Gene summary

Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. The type II keratins are clustered in a region of chromosome 12q13. [provided by RefSeq, Jul 2009]

Previous symbols:

KRT6E

MANE transcript

NM_173086.5

Inheritance

ClinVar variants

P:2U:112B:60

Top phenotype

Palmoplantar keratoderma, nonepidermolytic, focal or diffuse

gnomAD constraint

pLI —, LoF o/e 1.4

Max pathogenic AF

—

Genomic locus

chr12:52,468,516-52,473,805

External References & Databases

Ensembl (ENSG00000170465)

Transcript & Mutation Effects

hg38 • Region Span ~5.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

palmoplantar keratoderma, nonepidermolytic, focal or diffuseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014327

Submitter: Genomics England PanelApp

palmoplantar keratoderma, nonepidermolytic, focal or diffuseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014327

Submitter: Labcorp Genetics (formerly Invitae)

palmoplantar keratoderma, nonepidermolytic, focal or diffuseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014327

Submitter: PanelApp Australia

palmoplantar keratoderma, nonepidermolytic, focal or diffuseSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014327

Submitter: Orphanet

palmoplantar keratoderma, nonepidermolytic, focal or diffuseMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014327

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Palmoplantar keratoderma, nonepidermolytic, focal or diffuseAD

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: 19609311; 21801157; 23662636

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT6C variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 103

not providedTotal: 84

not specifiedTotal: 19

KRT6C-related disorderTotal: 10

Palmoplantar keratoderma, nonepidermolytic, focal or diffuseTotal: 2

Focal palmoplantar keratodermaTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

KRT6C-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173086.5. 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				34 clinvar	9 clinvar	43
missense	1 clinvar	1 clinvar	107 clinvar	13 clinvar	4 clinvar	126
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	1	1	112	47	13	174

Highest pathogenic variant AF is 0.0000020521325

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173086.5	RefSeq	NP_775109.2	9	MANE Select
ENST00000252250.7	Ensembl	ENSP00000252250.6	9	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology

Biological Process

keratinization
intermediate filament cytoskeleton organization
cornification

Molecular Function

structural molecule activity
protein binding

Cellular Component

cytosol
intermediate filament
keratin filament
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252250
Coding exons: 9
Length: 5270
Individuals with no LoFs: 125546
Homozygous LoFs: 5
Heterozygous LoFs: 197
Defined: 125748
p: 0.000804

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.19	366	307	1.19	0.0000190	3630
Missense (PolyPhen)		131	111.12	1.1789		1440
Synonymous	-2.30	160	127	1.26	0.00000770	1145
Loss of Function	-1.67	28	19.9	1.40	8.77e-7	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0053	0.0052	notable
Latino/Admixed American	0.00081	0.00078	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0012	0.00076	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00049	0.00047	rare
South Asian	0.00052	0.00052	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.292
RVIS EVS: -0.17
RVIS percentile EVS: 40.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.214

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High