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 (137 variants)
• Inborn_genetic_diseases (88 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				30	12	42
missense	13	7	121	12	10	163
nonsense		1	2			3
start loss						0
frameshift		1	2			3
splice donor/acceptor (+/-2bp)		4	4			8
Total	13	13	129	42	22

Highest pathogenic variant AF is 0.0000068158

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
0.0000703	0.981	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

Haploinsufficiency Scores

• pHI: 0.311
• hipred: Y
• hipred_score: 0.507
• ghis: 0.402

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

Mouse Genome Informatics

• Gene name: Krt6b
• Phenotype: digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

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