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 (12 variants)
• Pachyonychia congenita 3 (5 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	10	37
missense	10	2	51	6	12	81
nonsense		1				1
start loss						0
frameshift		1	1			2
inframe indel	2					2
splice donor/acceptor (+/-2bp)			1			1
splice region			1	2	7	10
non coding			1	3	8	12
Total	12	4	54	36	30

Highest pathogenic variant AF is 0.00000657

Variants in KRT6A

This is a list of pathogenic ClinVar variants found in the KRT6A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-52487732-G-T			Uncertain significance (Dec 25, 2022)
12-52487755-T-C			Uncertain significance (Feb 01, 2022)
12-52487760-G-C			Benign (Jan 22, 2024)
12-52487765-C-A		Pachyonychia congenita 3	Uncertain significance (Dec 11, 2023)
12-52487782-C-T		Inborn genetic diseases	Likely benign (Mar 31, 2024)
12-52487809-C-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
12-52487811-A-G			Likely benign (Oct 05, 2022)
12-52487812-T-A			Uncertain significance (Sep 10, 2023)
12-52487848-C-A			Benign (Jan 22, 2024)
12-52487848-C-T		KRT6A-related disorder	Likely benign (Jan 12, 2024)
12-52487850-C-T		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
12-52487881-C-T		Inborn genetic diseases	Uncertain significance (May 17, 2023)
12-52487886-C-A		Pachyonychia congenita 3	Uncertain significance (-)
12-52487903-G-GC			not provided (-)
12-52487905-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
12-52487906-G-A			Likely benign (Jun 14, 2023)
12-52487912-A-G			Likely benign (Jan 12, 2024)
12-52487916-G-C		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
12-52487957-T-G		Pachyonychia congenita 3	Pathogenic (Jul 01, 2012)
12-52488052-C-T			Likely benign (Jun 26, 2023)
12-52488062-T-C			Benign (Sep 01, 2022)
12-52488065-T-A			Uncertain significance (Mar 21, 2023)
12-52488072-T-C			Benign (Jan 25, 2024)
12-52488079-T-C		KRT6A-related disorder	Likely benign (Oct 28, 2022)
12-52488087-C-T		Inborn genetic diseases	Uncertain significance (Nov 24, 2023)

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