EZR
protein-codingezrin, the group of A-kinase anchoring proteins|FERM domain containing
Gene summary
The cytoplasmic peripheral membrane protein encoded by this gene functions as a protein-tyrosine kinase substrate in microvilli. As a member of the ERM protein family, this protein serves as an intermediate between the plasma membrane and the actin cytoskeleton. This protein plays a key role in cell surface structure adhesion, migration and organization, and it has been implicated in various human cancers. A pseudogene located on chromosome 3 has been identified for this gene. Alternatively spliced variants have also been described for this gene. [provided by RefSeq, Jul 2008]
- VIL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019502
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EZR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001111077.2. 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 | 18 | 5 | 25 | ||
| missense | 78 | 2 | 2 | 82 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 85 | 20 | 7 | 112 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001104547.1 | 13 | MANE Select | |
| Ensembl | ENSP00000356042.3 | 13 | MANE Select | |
| RefSeq | NP_003370.2 | 13 | Standard | |
| Ensembl | ENSP00000338934.7 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ezrb | Danio rerio | Structure: pronephric tubule Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Gastric acid secretion - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Pathogenic Escherichia coli infection - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- intestinal D-glucose absorption
- sphingosine-1-phosphate receptor signaling pathway
- cytoskeletal anchoring at plasma membrane
- leukocyte cell-cell adhesion
Molecular Function
- RNA binding
- actin binding
- protein binding
- microtubule binding
- protein C-terminus binding
Cellular Component
- fibrillar center
- ruffle
- immunological synapse
- uropod
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367075
- Coding exons
- 13
- Length
- 53672
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.984 | 307 | 360 | 0.854 | 0.0000231 | 3887 |
| Missense (PolyPhen) | 66 | 115.49 | 0.57148 | 1405 | ||
| Synonymous | -1.82 | 165 | 138 | 1.20 | 0.00000853 | 1044 |
| Loss of Function | 4.01 | 8 | 32.8 | 0.244 | 0.00000157 | 386 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000080 | 0.000070 | rare |
| South Asian | 0.00016 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}.;
Recessive Scores
- pRec
- 0.721
Intolerance Scores
- LoFtool
- 0.0624
- RVIS EVS
- -1.2
- RVIS percentile EVS
- 5.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |