KRT17

keratin 17, the group of Keratins, type I

Basic information

Region (hg38): 17:41619442-41624842

Previous symbols: [ "PCHC1" ]

Links

ENSG00000128422 ∙ NCBI:3872 ∙ OMIM:148069 ∙ HGNC:6427 ∙ Uniprot:Q04695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pachyonychia congenita 2 (Strong), mode of inheritance: AD
• sebocystomatosis (Strong), mode of inheritance: AD
• sebocystomatosis (Strong), mode of inheritance: AD
• pachyonychia congenita 2 (Strong), mode of inheritance: AD
• pachyonychia congenita (Supportive), mode of inheritance: AD
• sebocystomatosis (Supportive), mode of inheritance: AD
• sebocystomatosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Steatocystoma multiplex; Pachyonychia congenita 2	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	Dental; Dermatologic	7529318; 7539673; 9008238; 11886499; 20301457; 22264670

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT17 gene.

• not provided (5 variants)
• Pachyonychia congenita 2 (4 variants)
• Pachyonychia congenita 2;Steatocystoma multiplex (1 variants)
• Abnormality of the skin (1 variants)
• Anonychia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT17 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				14	10	24
missense	5	1	32	13	8	59
nonsense			1	1		2
start loss			1			1
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region	1			5	5	11
non coding				4	5	9
Total	5	2	34	32	23

Highest pathogenic variant AF is 0.0000131

Variants in KRT17

This is a list of pathogenic ClinVar variants found in the KRT17 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-41619618-C-T			Benign (Jan 29, 2024)
17-41619619-T-C			Uncertain significance (Jun 23, 2023)
17-41619622-C-A			Benign (Sep 27, 2022)
17-41619622-C-T			Likely benign (Nov 19, 2022)
17-41619623-G-A			Likely benign (Dec 21, 2023)
17-41619654-T-C			Likely benign (Dec 31, 2019)
17-41619667-C-A			Uncertain significance (Nov 10, 2023)
17-41619677-G-A			Uncertain significance (Dec 27, 2022)
17-41619706-AA-GC			Likely benign (Jan 16, 2024)
17-41620536-G-A			Likely benign (Aug 17, 2023)
17-41620547-T-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
17-41620558-G-A		Inborn genetic diseases	Likely benign (Mar 07, 2024)
17-41620565-GA-G			Benign (Jan 25, 2024)
17-41620565-G-GA			Benign (Jan 20, 2024)
17-41620565-G-GAA		KRT17-related disorder	Likely benign (May 01, 2019)
17-41620677-A-G			not provided (-)
17-41620683-C-T			Uncertain significance (Jun 19, 2023)
17-41620713-C-T			Likely benign (Jul 27, 2023)
17-41620714-G-A			Likely benign (Mar 26, 2023)
17-41620728-A-G			not provided (-)
17-41620739-G-T			Uncertain significance (Jul 01, 2022)
17-41620779-G-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
17-41620795-C-T			Benign (Dec 23, 2023)
17-41620847-T-C			Likely benign (Jul 07, 2023)
17-41620876-C-T			Likely benign (Oct 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT17	protein_coding	protein_coding	ENST00000311208	8	5406

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-11	0.0884	125612	0	136	125748	0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.492	283	261	1.09	0.0000187	2808
Missense in Polyphen		62	67.323	0.92093		892
Synonymous	-1.19	125	109	1.14	0.00000710	877
Loss of Function	0.401	18	19.9	0.903	0.00000106	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00125	0.00125
Ashkenazi Jewish	0.000893	0.000893
East Asian	0.000110	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000585	0.000580
Middle Eastern	0.000110	0.000109
South Asian	0.000458	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state (By similarity). Modulates the function of TNF-alpha in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway (By similarity). Involved in tissue repair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial "stem cells". Acts as a promoter of epithelial proliferation by acting a regulator of immune response in skin: promotes Th1/Th17-dominated immune environment contributing to the development of basaloid skin tumors (By similarity). May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation. {ECO:0000250|UniProtKB:Q9QWL7, ECO:0000269|PubMed:10844551, ECO:0000269|PubMed:15795121, ECO:0000269|PubMed:16713453}.
• Disease: DISEASE: Pachyonychia congenita 2 (PC2) [MIM:167210]: An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma and hyperhidrosis, follicular hyperkeratosis, multiple epidermal cysts, absent/sparse eyebrow and body hair, and by the presence of natal teeth. {ECO:0000269|PubMed:10571744, ECO:0000269|PubMed:11348474, ECO:0000269|PubMed:11874497, ECO:0000269|PubMed:11886499, ECO:0000269|PubMed:15102078, ECO:0000269|PubMed:15795125, ECO:0000269|PubMed:16250206, ECO:0000269|PubMed:16620218, ECO:0000269|PubMed:16625196, ECO:0000269|PubMed:17719747, ECO:0000269|PubMed:18547302, ECO:0000269|PubMed:19470054, ECO:0000269|PubMed:21326300, ECO:0000269|PubMed:23278621, ECO:0000269|PubMed:23855588, ECO:0000269|PubMed:7539673, ECO:0000269|PubMed:9008238, ECO:0000269|PubMed:9767294}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Steatocystoma multiplex (SM) [MIM:184500]: Disease characterized by round or oval cystic tumors widely distributed on the back, anterior trunk, arms, scrotum, and thighs. {ECO:0000269|PubMed:16620218, ECO:0000269|PubMed:9008238, ECO:0000269|PubMed:9767294}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=KRT16 and KRT17 are coexpressed only in pathological situations such as metaplasias and carcinomas of the uterine cervix and in psoriasis vulgaris.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);Keratinization;Developmental Biology;EGFR1;Glucocorticoid receptor regulatory network (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.397
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt17
• Phenotype: digestive/alimentary phenotype; pigmentation phenotype; 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); cellular phenotype; craniofacial phenotype; growth/size/body region 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)

Gene ontology

• Biological process: cytoskeleton organization;signal transduction;epidermis development;hair follicle morphogenesis;keratinization;cornification
• Cellular component: cytosol;intermediate filament;intermediate filament cytoskeleton;extracellular exosome
• Molecular function: structural constituent of cytoskeleton;protein binding;MHC class II receptor activity;MHC class II protein binding