ECT2
protein-codingepithelial cell transforming 2, the group of Dbl family Rho GEFs
Gene summary
The protein encoded by this gene is a guanine nucleotide exchange factor and transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. The expression of this gene is elevated with the onset of DNA synthesis and remains elevated during G2 and M phases. In situ hybridization analysis showed that expression is at a high level in cells undergoing mitosis in regenerating liver. Thus, this protein is expressed in a cell cycle-dependent manner during liver regeneration, and is thought to have an important role in the regulation of cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~70.8 kbGenCC 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 ECT2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001258315.2. 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 | 1 | 3 | |||
| missense | 93 | 4 | 97 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 106 | 4 | 1 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001245244.1 | 24 | MANE Select | |
| Ensembl | ENSP00000376457.3 | 24 | MANE Select | |
| RefSeq | NP_001245245.1 | 23 | Standard | |
| RefSeq | NP_001336023.1 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ect2 | Danio rerio | Structure: trunk Quality: curved dorsal abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric Cancer Network 1
- Signaling by GPCR
- Signal Transduction
- Rho GTPase cycle
- Signaling by Rho GTPases
Biological Process
- mitotic cytokinesis
- cell morphogenesis
- G protein-coupled receptor signaling pathway
- protein transport
- activation of protein kinase activity
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
- protein homodimerization activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
- cell-cell junction
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392692
- Coding exons
- 24
- Length
- 70793
- Individuals with no LoFs
- 125695
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 52
- Defined
- 125747
- p
- 0.000207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.74 | 360 | 466 | 0.773 | 0.0000233 | 6012 |
| Missense (PolyPhen) | 114 | 195.14 | 0.58419 | 2442 | ||
| Synonymous | -0.680 | 161 | 150 | 1.07 | 0.00000712 | 1684 |
| Loss of Function | 3.54 | 24 | 51.4 | 0.467 | 0.00000285 | 657 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00046 | 0.00043 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00023 | 0.00023 | rare |
| South Asian | 0.00024 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)- induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.699
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.8
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.850
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |