KRT8

keratin 8, the group of Keratins, type II

Basic information

Region (hg38): 12:52897187-52949954

Links

ENSG00000170421 ∙ NCBI:3856 ∙ OMIM:148060 ∙ HGNC:6446 ∙ Uniprot:P05787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cirrhosis, familial (Limited), mode of inheritance: Unknown
• cirrhosis, familial (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT8 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				5	3	8
missense			21	6	4	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	21	11	9

Variants in KRT8

This is a list of pathogenic ClinVar variants found in the KRT8 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-52897390-C-T			not provided (-)
12-52897397-G-A			not provided (-)
12-52897420-G-A			not provided (-)
12-52897442-C-T		KRT8-related disorder	Benign (Dec 31, 2019)
12-52897468-C-T		Hepatitis C virus, susceptibility to • not specified	Uncertain significance (Jan 02, 2024)
12-52897488-C-A		not specified	Uncertain significance (Dec 27, 2023)
12-52897520-G-A			not provided (-)
12-52897524-G-A			Likely benign (Dec 01, 2023)
12-52897540-G-A		Hepatitis C virus, susceptibility to	Likely benign (Sep 23, 2021)
12-52897546-G-C		not specified	Uncertain significance (Dec 14, 2022)
12-52897550-C-T		not specified	Uncertain significance (Jan 24, 2024)
12-52897575-G-A			Likely benign (Aug 28, 2018)
12-52897580-C-T		KRT8-related disorder	Benign (Dec 31, 2019)
12-52897592-G-T		not specified	Uncertain significance (Jul 09, 2024)
12-52897615-C-A			Uncertain significance (Jun 26, 2019)
12-52898441-C-T			not provided (-)
12-52898449-TG-T			not provided (-)
12-52898452-G-A			Benign (Dec 31, 2019)
12-52898633-T-A			not provided (-)
12-52898678-C-T			Uncertain significance (-)
12-52898707-T-C		not specified	Uncertain significance (Mar 31, 2023)
12-52898743-C-T			Likely benign (Apr 01, 2023)
12-52898744-G-A		not specified	Likely benign (Jul 02, 2024)
12-52898753-C-T			not provided (-)
12-52898776-G-A		not specified	Uncertain significance (Apr 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT8	protein_coding	protein_coding	ENST00000552150	9	52762

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.36e-8	0.710	125654	1	93	125748	0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.779	272	311	0.876	0.0000203	3354
Missense in Polyphen		36	49.37	0.72918		800
Synonymous	-0.872	145	132	1.10	0.00000871	1008
Loss of Function	1.32	15	21.6	0.693	0.00000106	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000581	0.000563
Middle Eastern	0.0000544	0.0000544
South Asian	0.000262	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle. {ECO:0000269|PubMed:16000376}.
• Disease: DISEASE: Cirrhosis (CIRRH) [MIM:215600]: A liver disease characterized by severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, and marked deposits of copper. Clinical features include abdomen swelling, jaundice and pulmonary hypertension. {ECO:0000269|PubMed:12724528}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;Keratinization;Developmental Biology;EGFR1;Signaling mediated by p38-alpha and p38-beta (Consensus)

Recessive Scores

• pRec: 0.832

Intolerance Scores

• loftool: 0.168
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.96

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.489
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.890

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt8
• Phenotype: immune system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system 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); liver/biliary system phenotype; embryo phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: viral process;keratinization;tumor necrosis factor-mediated signaling pathway;sarcomere organization;response to hydrostatic pressure;response to other organism;cell differentiation involved in embryonic placenta development;cornification;extrinsic apoptotic signaling pathway;hepatocyte apoptotic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;intermediate filament;cell-cell junction;dystrophin-associated glycoprotein complex;apicolateral plasma membrane;nuclear matrix;Z disc;sarcolemma;costamere;keratin filament;intermediate filament cytoskeleton;extracellular exosome
• Molecular function: structural molecule activity;protein binding;protein-containing complex binding;scaffold protein binding