KRT18

protein-coding

keratin 18, the group of Keratins, type I

Gene summary

KRT18 encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000224.3

Inheritance

ClinVar variants

P:1U:52B:3

Top phenotype

Hepatitis C virus, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr12:52,948,871-52,952,906

External References & Databases

Ensembl (ENSG00000111057)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cirrhosis, familialLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007329

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT18 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 18

Hepatitis C virus, susceptibility toTotal: 3

Cirrhosis, familialTotal: 3

Cirrhosis, noncryptogenic, susceptibility toTotal: 1

Cirrhosis, cryptogenicTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000224.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	1 clinvar		6
missense	1 clinvar		46 clinvar	1 clinvar		48
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	52	2	1	56

Highest pathogenic variant AF is 0.00032159002

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000224.3	RefSeq	NP_000215.1	7	MANE Select
ENST00000388835.4	Ensembl	ENSP00000373487.3	7	MANE Select
NM_199187.2	RefSeq	NP_954657.1	7	Standard
ENST00000388837.6	Ensembl	ENSP00000373489.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Estrogen signaling pathway - Homo sapiens (human)
Pathogenic Escherichia coli infection - Homo sapiens (human)
Pathogenic Escherichia coli infection
Keratinization
Developmental Biology

Biological Process

cell cycle
anatomical structure morphogenesis
viral process
keratinization
tumor necrosis factor-mediated signaling pathway

Molecular Function

RNA binding
structural molecule activity
protein binding
scaffold protein binding
cadherin binding involved in cell-cell adhesion

Cellular Component

nucleolus
cytoplasm
microtubule organizing center
cytosol
intermediate filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000388835
Coding exons: 7
Length: 4031
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125700
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	202	248	0.815	0.0000152	2776
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.0333
RVIS EVS: -0.27
RVIS percentile EVS: 34.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.948

Gene Damage Prediction

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