KRT6C

keratin 6C, the group of Keratins, type II

Basic information

Region (hg38): 12:52468516-52473805

Previous symbols: [ "KRT6E" ]

Links

ENSG00000170465 ∙ NCBI:286887 ∙ OMIM:612315 ∙ HGNC:20406 ∙ Uniprot:P48668 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• palmoplantar keratoderma, nonepidermolytic, focal or diffuse (Moderate), mode of inheritance: AD
• palmoplantar keratoderma, nonepidermolytic, focal or diffuse (Strong), mode of inheritance: AD
• palmoplantar keratoderma, nonepidermolytic, focal or diffuse (Strong), mode of inheritance: AD
• palmoplantar keratoderma, nonepidermolytic, focal or diffuse (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Palmoplantar keratoderma, nonepidermolytic, focal or diffuse	AD	General	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	Dermatologic	19609311; 21801157; 23662636

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT6C gene.

• Inborn_genetic_diseases (99 variants)
• not_provided (81 variants)
• KRT6C-related_disorder (9 variants)
• Palmoplantar_keratoderma,_nonepidermolytic,_focal_or_diffuse (2 variants)
• Focal_palmoplantar_keratoderma (2 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT6C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173086.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	11	36
missense		1	102	13	4	120
nonsense			2			2
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)						0
Total	0	1	106	38	15

Highest pathogenic variant AF is 0.0000020521325

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT6C	protein_coding	protein_coding	ENST00000252250	9	5270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125546	5	197	125748	0.000804

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.19	366	307	1.19	0.0000190	3630
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00608	0.00599
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00119	0.000761
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000490	0.000475
Middle Eastern	0.00119	0.000761
South Asian	0.000525	0.000523
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Pathway: Keratinization;Developmental Biology (Consensus)

Intolerance Scores

• loftool: 0.292
• rvis_EVS: -0.17
• rvis_percentile_EVS: 40.65

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.214

Gene Damage Prediction

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

Gene ontology

• Biological process: keratinization;intermediate filament cytoskeleton organization;cornification
• Cellular component: cytosol;intermediate filament;keratin filament;extracellular exosome
• Molecular function: structural molecule activity;protein binding