KRT8

protein-coding

keratin 8, the group of Keratins, type II

Gene summary

This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

MANE transcript

NM_002273.4

Inheritance

AR, AD

ClinVar variants

U:64B:19

Top phenotype

KRT8-related disorder

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr12:52,897,187-52,949,954

External References & Databases

Ensembl (ENSG00000170421)

Transcript & Mutation Effects

hg38 • Region Span ~52.8 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)

cirrhosis, familialLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007329

Submitter: PanelApp Australia

cirrhosis, familialLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007329

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT8 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 26

KRT8-related disorderTotal: 8

Hepatitis C virus, susceptibility toTotal: 5

Cirrhosis, cryptogenicTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Inflammatory bowel diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002273.4. 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			2 clinvar	7 clinvar	1 clinvar	10
missense			60 clinvar	9 clinvar	2 clinvar	71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	64	16	3	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002273.4	RefSeq	NP_002264.1	8	MANE Select
ENST00000692008.1	Ensembl	ENSP00000509398.1	8	MANE Select
NM_001256282.2	RefSeq	NP_001243211.1	9	Standard
NM_001256293.2	RefSeq	NP_001243222.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Primary Focal Segmental Glomerulosclerosis FSGS
Keratinization
Developmental Biology
EGFR1
Signaling mediated by p38-alpha and p38-beta

Biological Process

viral process
keratinization
tumor necrosis factor-mediated signaling pathway
sarcomere organization
response to hydrostatic pressure

Molecular Function

structural molecule activity
protein binding
protein-containing complex binding
scaffold protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
intermediate filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000552150
Coding exons: 9
Length: 52762
Individuals with no LoFs: 125654
Homozygous LoFs: 1
Heterozygous LoFs: 93
Defined: 125748
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.779	272	311	0.876	0.0000203	3354
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.0014	0.0014	notable
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00058	0.00056	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.832

Intolerance Scores

LoFtool: 0.168
RVIS EVS: 0.53
RVIS percentile EVS: 80.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.890

Gene Damage Prediction

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