UNC5B
protein-codingunc-5 netrin receptor B, the group of Ig-like cell adhesion molecule family|I-set domain containing
Gene summary
This gene encodes a member of the netrin family of receptors. This particular protein mediates the repulsive effect of netrin-1 and is a vascular netrin receptor. This encoded protein is also in a group of proteins called dependence receptors (DpRs) which are involved in pro- and anti-apoptotic processes. Many DpRs are involved in embryogenesis and in cancer progression. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~90.3 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 UNC5B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_170744.5. 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 | 3 | 3 | 6 | |||
| missense | 187 | 12 | 199 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 4 | 1 | 5 | |||
| Total | 0 | 0 | 195 | 15 | 2 | 212 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_734465.2 | 17 | MANE Select | |
| Ensembl | ENSP00000334329.6 | 17 | MANE Select | |
| RefSeq | NP_001231818.1 | 16 | Standard | |
| Ensembl | ENSP00000362288.4 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| unc5b | Danio rerio | Structure: parachordal vessel Quality: aplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- Caspase activation via extrinsic apoptotic signalling pathway
- Apoptosis
- Programmed Cell Death
Biological Process
- angiogenesis
- apoptotic process
- positive regulation of phosphatidylinositol 3-kinase signaling
- anterior/posterior axon guidance
- netrin-activated signaling pathway
Molecular Function
- netrin receptor activity
- protein binding
Cellular Component
- plasma membrane
- integral component of membrane
- membrane raft
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000335350
- Coding exons
- 17
- Length
- 90295
- Individuals with no LoFs
- 123616
- Homozygous LoFs
- 59
- Heterozygous LoFs
- 2073
- Defined
- 125748
- p
- 0.00851
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0523 | 602 | 606 | 0.994 | 0.0000402 | 6058 |
| Missense (PolyPhen) | 201 | 223.47 | 0.89945 | 2257 | ||
| Synonymous | -0.831 | 279 | 262 | 1.07 | 0.0000183 | 1942 |
| Loss of Function | 3.58 | 19 | 44.9 | 0.423 | 0.00000220 | 481 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.017 | 0.017 | notable |
| Latino/Admixed American | 0.036 | 0.034 | notable |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.0093 | 0.0091 | notable |
| Finnish | 0.0025 | 0.0024 | notable |
| European (Non-Finnish) | 0.0031 | 0.0031 | notable |
| South Asian | 0.0028 | 0.0027 | notable |
| Other | 0.0066 | 0.0064 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis. Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (By similarity). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:12598906). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity). {ECO:0000250|UniProtKB:O08722, ECO:0000250|UniProtKB:Q8K1S3, ECO:0000269|PubMed:12598906}.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.543
- RVIS EVS
- -1.63
- RVIS percentile EVS
- 2.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.439
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |