ANGPT4
protein-codingangiopoietin 4, the group of Receptor ligands|Fibrinogen C domain containing
Gene summary
Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. The protein encoded by this gene functions as an agonist and is an angiopoietin. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.4 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 ANGPT4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015985.4. 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 | 1 | 2 | 3 | |||
| missense | 69 | 8 | 1 | 78 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 70 | 9 | 3 | 82 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057069.1 | 9 | MANE Select | |
| Ensembl | ENSP00000371347.3 | 9 | MANE Select | |
| RefSeq | NP_001309738.1 | 8 | Standard | |
| Ensembl | ENSP00000548168.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- HIF-1 signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
Biological Process
- angiogenesis
- endothelial cell proliferation
- activation of transmembrane receptor protein tyrosine kinase activity
- Notch signaling pathway
- positive regulation of endothelial cell migration
Molecular Function
- transmembrane receptor protein tyrosine kinase activator activity
- receptor tyrosine kinase binding
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381922
- Coding exons
- 9
- Length
- 43682
- Individuals with no LoFs
- 125469
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 278
- Defined
- 125748
- p
- 0.00111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.126 | 292 | 286 | 1.02 | 0.0000159 | 3272 |
| Missense (PolyPhen) | 82 | 88.966 | 0.9217 | 1002 | ||
| Synonymous | 0.365 | 116 | 121 | 0.958 | 0.00000717 | 962 |
| Loss of Function | 0.296 | 23 | 24.6 | 0.936 | 0.00000106 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0.010 | 0.010 | notable |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis. {ECO:0000269|PubMed:15284220}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.773
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.766
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |