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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UNC5A
unc-5 netrin receptor A
Chromosome 5 · 5q35.2
NCBI Gene: 90249Ensembl: ENSG00000113763.12HGNC: HGNC:12567UniProt: H0Y8R2
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedReceptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
neuron projection membraneneuronal cell body membraneneuron projection developmentanterior/posterior axon guidanceankylosing spondylitisexostosissmoking initiationnon-small cell lung carcinoma
✦AI Summary

UNC5A encodes a netrin receptor that serves dual functions in neural development and cancer biology. Primarily, UNC5A functions as an axon guidance receptor that mediates repulsion of neuronal growth cones during nervous system development in response to netrin-1 1. The protein promotes neurite outgrowth and requires association with DCC receptor to trigger repulsive signaling 1. UNC5A also acts as a dependence receptor, inducing apoptosis when not bound to its netrin ligand 1. Beyond neural development, UNC5A functions as a tumor suppressor across multiple cancer types. It is a transcriptional target of p53 and regulates p53-dependent apoptosis through caspase-3 activation 2. In non-small cell lung cancer, UNC5A expression is epigenetically silenced through promoter hypermethylation, and its loss promotes cell proliferation, migration, and invasion via PI3K/Akt pathway activation 3. Similarly, UNC5A functions as a tumor suppressor in bladder cancer, where low expression correlates with reduced response to DNA-damaging chemotherapy 4. In breast cancer, UNC5A restricts cellular plasticity and prevents luminal to basal subtype conversion, with its depletion leading to enhanced metastatic potential 5. Pan-cancer analyses reveal UNC5A as a potential biomarker associated with patient outcomes and immune infiltration patterns 6.

Sources cited
1
UNC5A mediates axon repulsion in response to netrin-1 and requires DCC for repulsive signaling
PMID: 18269208
2
UNC5A is a p53 transcriptional target that induces apoptosis through caspase-3 activation
PMID: 20372800
3
UNC5A is epigenetically silenced in NSCLC and functions as tumor suppressor via PI3K/Akt pathway
PMID: 33100860
4
UNC5A functions as tumor suppressor in bladder cancer and affects chemotherapy response
PMID: 24737586
5
UNC5A restricts breast cancer plasticity and prevents luminal to basal conversion
PMID: 29720215
6
UNC5A serves as pan-cancer biomarker associated with patient outcomes and immune infiltration
PMID: 36551254
Disease Associationsⓘ20
ankylosing spondylitisOpen Targets
0.33Weak
exostosisOpen Targets
0.23Weak
smoking initiationOpen Targets
0.18Weak
non-small cell lung carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
hereditary neuropathy with liability to pressure palsiesOpen Targets
0.04Suggestive
Autosomal recessive spastic paraplegia type 25Open Targets
0.04Suggestive
hereditary spastic paraplegia 25Open Targets
0.04Suggestive
amyotrophic lateral sclerosis type 22Open Targets
0.04Suggestive
colorectal carcinomaOpen Targets
0.04Suggestive
craniofacial conodysplasiaOpen Targets
0.04Suggestive
microcephaly 25, primary, autosomal recessiveOpen Targets
0.04Suggestive
prostate adenocarcinomaOpen Targets
0.03Suggestive
diastematomyeliaOpen Targets
0.03Suggestive
central nervous system cancerOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DCCProtein interaction100%NEO1Protein interaction100%NTN1Protein interaction100%MAGED1Protein interaction97%NTN4Protein interaction91%PTPN11Protein interaction90%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
29%
Lung
1%
Ovary
1%
Liver
1%
Heart
1%
Gene Interaction Network
Click a node to explore
UNC5ADCCNEO1NTN1MAGED1NTN4PTPN11
PROTEIN STRUCTURE
Preparing viewer…
PDB4V2A · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.17–0.35]
RankingsWhere UNC5A stands among ~20K protein-coding genes
  • #13,562of 20,598
    Most Researched23
  • #1,512of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedUNC5A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GPC3-Unc5 receptor complex structure and role in cell migration.
PMID: 36240740
Cell · 2022
1.00
2
Dependence receptor UNC5A restricts luminal to basal breast cancer plasticity and metastasis.
PMID: 29720215
Breast Cancer Res · 2018
0.90
3
A Systematic Analysis of the Role of Unc-5 Netrin Receptor A (UNC5A) in Human Cancers.
PMID: 36551254
Biomolecules · 2022
0.80
4
Netrins and their receptors.
PMID: 18269208
Adv Exp Med Biol · 2007
0.70
5
UNC5A, an epigenetically silenced gene, functions as a tumor suppressor in non-small cell lung cancer.
PMID: 33100860
Saudi J Biol Sci · 2020
0.60