KRT6A

keratin 6A, the group of Keratins, type II

Basic information

Region (hg38): 12:52487176-52493257

Previous symbols: [ "KRT6C", "KRT6D" ]

Links

ENSG00000205420 ∙ NCBI:3853 ∙ OMIM:148041 ∙ HGNC:6443 ∙ Uniprot:P02538 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pachyonychia congenita 3 (Strong), mode of inheritance: AD
• pachyonychia congenita 3 (Strong), mode of inheritance: AD
• pachyonychia congenita (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pachyonychia congenita 3	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	7545493; 11886499; 20301457; 22098151; 22264670; 22668561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT6A gene.

• not_provided (147 variants)
• Inborn_genetic_diseases (94 variants)
• Pachyonychia_congenita_3 (28 variants)
• KRT6A-related_disorder (18 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT6A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005554.4. 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				31	12	43
missense	14	7	131	11	11	174
nonsense		1	2			3
start loss						0
frameshift		1	2			3
splice donor/acceptor (+/-2bp)		4	4			8
Total	14	13	139	42	23

Highest pathogenic variant AF is 0.0000068158047

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT6A	protein_coding	protein_coding	ENST00000330722	9	6084

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.948	367	319	1.15	0.0000203	3663
Missense in Polyphen		119	101.99	1.1668		1396
Synonymous	-3.34	183	134	1.37	0.00000852	1165
Loss of Function	2.09	10	20.1	0.497	8.97e-7	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Epidermis-specific type I keratin involved in wound healing. Involved in the activation of follicular keratinocytes after wounding, while it does not play a major role in keratinocyte proliferation or migration. Participates in the regulation of epithelial migration by inhibiting the activity of SRC during wound repair. {ECO:0000250|UniProtKB:P50446}.
• Pathway: Ectoderm Differentiation;Keratinization;Developmental Biology;EGFR1 (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.0244
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.82

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.920

Gene Damage Prediction

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

Gene ontology

• Biological process: negative regulation of cytolysis by symbiont of host cells;morphogenesis of an epithelium;cytoskeleton organization;positive regulation of cell population proliferation;cell differentiation;keratinization;wound healing;defense response to Gram-positive bacterium;cytolysis in other organism involved in symbiotic interaction;antimicrobial humoral immune response mediated by antimicrobial peptide;cornification;negative regulation of entry of bacterium into host cell
• Cellular component: nucleus;cytosol;membrane;keratin filament;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding