UNC5A
protein-codingunc-5 netrin receptor A, the group of I-set domain containing|Ig-like cell adhesion molecule family
Gene summary
UNC5A belongs to a family of netrin-1 (MIM 601614) receptors thought to mediate the chemorepulsive effect of netrin-1 on specific axons. For more information on UNC5 proteins, see UNC5C (MIM 603610).[supplied by OMIM, Apr 2004]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~70.4 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 UNC5A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133369.3. 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 | 1 | 2 | |||
| missense | 90 | 1 | 91 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 92 | 2 | 0 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_588610.2 | 15 | MANE Select | |
| Ensembl | ENSP00000332737.4 | 15 | MANE Select | |
| Ensembl | ENSP00000421795.2 | 16 | Standard | |
| Ensembl | ENSP00000421795.2 | 16 | Standard |
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
- apoptotic process
- axon guidance
- neuron projection development
- anterior/posterior axon guidance
- netrin-activated signaling pathway
Molecular Function
- netrin receptor activity
Cellular Component
- plasma membrane
- integral component of membrane
- intrinsic component of plasma membrane
- neuron projection membrane
- neuronal cell body membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329542
- Coding exons
- 15
- Length
- 70420
- Individuals with no LoFs
- 125689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125695
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.75 | 354 | 533 | 0.665 | 0.0000345 | 5448 |
| Missense (PolyPhen) | 117 | 205.25 | 0.57004 | 1975 | ||
| Synonymous | 0.421 | 224 | 232 | 0.965 | 0.0000157 | 1765 |
| Loss of Function | 5.26 | 3 | 38.0 | 0.0789 | 0.00000189 | 406 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for netrin required for axon guidance. Functions in the netrin signaling pathway and promotes neurite outgrowth in response to NTN1. Mediates axon repulsion of neuronal growth cones in the developing nervous system in response to netrin. Axon repulsion in growth cones may be mediated by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. {ECO:0000250|UniProtKB:O08721}.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- LoFtool
- 0.0725
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.857
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |