KRT18

keratin 18, the group of Keratins, type I

Basic information

Region (hg38): 12:52948871-52952906

Links

ENSG00000111057 ∙ NCBI:3875 ∙ OMIM:148070 ∙ HGNC:6430 ∙ Uniprot:P05783 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT18 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT18 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				1		1
missense			18	1		19
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	18	2	1

Variants in KRT18

This is a list of pathogenic ClinVar variants found in the KRT18 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-52949159-C-T			not provided (-)
12-52949184-C-T		not specified	Uncertain significance (Jun 11, 2021)
12-52949230-C-T			Likely benign (Mar 01, 2022)
12-52949256-C-T		not specified	Uncertain significance (Nov 27, 2023)
12-52949280-A-C		not specified	Uncertain significance (Nov 12, 2021)
12-52949307-G-C		Hepatitis C virus, susceptibility to	not provided (-)
12-52949347-G-GA		not specified	Benign (Jan 02, 2020)
12-52949365-CACCGGGATAGCCGGGGGTCTGGCA-C			not provided (-)
12-52949379-G-C		Cirrhosis, familial	Uncertain significance (Nov 27, 2019)
12-52949441-C-T		not specified	Benign (-)
12-52949447-G-C		not specified	Benign (-)
12-52949455-C-T		Hepatitis C virus, susceptibility to	not provided (-)
12-52949473-C-G		not specified	Benign (-)
12-52949480-A-G			not provided (-)
12-52949529-A-G		not specified	Uncertain significance (Mar 24, 2023)
12-52949556-A-T		Cirrhosis, cryptogenic • Cirrhosis, noncryptogenic, susceptibility to	Pathogenic; risk factor (May 13, 2003)
12-52950324-C-G			not provided (-)
12-52950358-A-G			not provided (-)
12-52950448-G-A			not provided (-)
12-52950767-C-G		not specified	Uncertain significance (Jun 03, 2024)
12-52950790-G-A		Cirrhosis, familial	Uncertain significance (Jun 03, 2020)
12-52950802-C-T		not specified	Uncertain significance (Jun 22, 2021)
12-52950806-G-A		not specified	Uncertain significance (Nov 03, 2022)
12-52950810-G-T		not specified	Uncertain significance (Dec 15, 2023)
12-52950848-A-G		Cirrhosis, familial	Uncertain significance (Mar 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KRT18	protein_coding	protein_coding	ENST00000388835	7	4031

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.735	0.265	125697	0	3	125700	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	202	248	0.815	0.0000152	2776
Missense in Polyphen		14	22.33	0.62696		429
Synonymous	-0.488	109	103	1.06	0.00000595	870
Loss of Function	3.21	3	17.5	0.171	9.46e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection. {ECO:0000250, ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113}.
• 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, ECO:0000269|PubMed:9011570}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathogenic Escherichia coli infection;Keratinization;Developmental Biology;EGFR1;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.0333
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.809
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.948

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Krt18
• 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; growth/size/body region phenotype

Gene ontology

• Biological process: cell cycle;anatomical structure morphogenesis;viral process;keratinization;tumor necrosis factor-mediated signaling pathway;Golgi to plasma membrane CFTR protein transport;negative regulation of apoptotic process;intermediate filament cytoskeleton organization;cornification;extrinsic apoptotic signaling pathway;hepatocyte apoptotic process;cell-cell adhesion
• Cellular component: nucleolus;cytoplasm;microtubule organizing center;cytosol;intermediate filament;cell-cell adherens junction;centriolar satellite;keratin filament;perinuclear region of cytoplasm;extracellular exosome;cell periphery
• Molecular function: RNA binding;structural molecule activity;protein binding;scaffold protein binding;cadherin binding involved in cell-cell adhesion