EPPK1

protein-coding

epiplakin 1, the group of Plakins

Gene summary

The protein encoded by this gene belongs to the plakin family of proteins, which play a role in the organization of cytoskeletal architecture. This family member is composed of several highly homologous plakin repeats. It may function to maintain the integrity of keratin intermediate filament networks in epithelial cells. Studies of the orthologous mouse protein suggest that it accelerates keratinocyte migration during wound healing. [provided by RefSeq, Oct 2013]

MANE transcript

NM_031308.4

Inheritance

—

ClinVar variants

U:356B:226

Top phenotype

EPPK1-related disorder

Max pathogenic AF

—

Genomic locus

chr8:143,857,324-143,878,467

External References & Databases

Ensembl (ENSG00000261150)

Transcript & Mutation Effects

hg38 • Region Span ~21.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPPK1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 390

EPPK1-related disorderTotal: 196

not providedTotal: 26

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

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031308.4. 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				121 clinvar	14 clinvar	135
missense			352 clinvar	59 clinvar	27 clinvar	438
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar	2 clinvar	3 clinvar	7
splice donor/acceptor (+/-2bp)						0
Total	0	0	356	182	44	582

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031308.4	RefSeq	NP_112598.3	1	MANE Select
ENST00000615648.2	Ensembl	ENSP00000484472.1	1	MANE Select
ENST00000568225.2	Ensembl	ENSP00000456124.2	1	Standard
ENST00001137711.1	Ensembl	ENSP00000814811.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

negative regulation of keratinocyte proliferation
negative regulation of cell migration
wound healing
intermediate filament cytoskeleton organization
intermediate filament organization

Molecular Function

RNA binding
structural molecule activity
cytoskeletal protein binding
intermediate filament binding
keratin filament binding

Cellular Component

cytoplasm
cytoskeleton
intermediate filament
bicellular tight junction
membrane

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress (PubMed:15671067, PubMed:27206504, PubMed:23398049). In response to mechanical stress like wound healing, is associated with the machinery for cellular motility by slowing down keratinocyte migration and proliferation and accelerating keratin bundling in proliferating keratinocytes thus contributing to tissue architecture (PubMed:27206504, PubMed:23398049). However in wound healing in corneal epithelium also positively regulates cell differentiation and proliferation and negatively regulates migration thereby controlling corneal epithelium morphogenesis and integrity. In response to cellular stress, plays a role in keratin filament reorganization, probably by protecting keratin filaments against disruption. During liver and pancreas injuries, plays a protective role by chaperoning disease-induced intermediate filament reorganization (By similarity). {ECO:0000250|UniProtKB:Q8R0W0, ECO:0000269|PubMed:15671067, ECO:0000269|PubMed:23398049, ECO:0000269|PubMed:27206504}.;

Essentials

Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High