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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ROR1
receptor tyrosine kinase like orphan receptor 1
Chromosome 1 · 1p31.3
NCBI Gene: 4919Ensembl: ENSG00000185483.13HGNC: HGNC:10256UniProt: Q01973
141PubMed Papers
21Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinaseReceptor
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cell population proliferationpositive regulation of canonical NF-kappaB signal transductionATP bindingsignaling receptor complexhearing loss, autosomal recessivecervical carcinomadiffuse large B-cell lymphomaAbnormality of the skeletal system
✦AI Summary

ROR1 is a receptor tyrosine kinase-like orphan receptor with very low kinase activity in vivo 1. It functions primarily as a Wnt receptor, binding WNT5A ligand to activate downstream NF-κB signaling and inhibit canonical WNT3A-mediated pathways 12. In the inner ear, ROR1 is crucial for spiral ganglion neuron innervation of auditory hair cells 2, with mutations causing autosomal recessive deafness 2. ROR1 also forms complexes with ERBB2 via IGFBP5 ligand to enhance CREB oncogenic signaling 3. In cancer biology, ROR1 supports cancer stem cell maintenance through noncanonical WNT signaling, promoting epithelial-mesenchymal transition and chemoresistance 45. Cell surface ROR1 is expressed on ovarian, triple-negative breast, and lung adenocarcinomas, though expression on normal tissues including parathyroid, pancreatic islets, and gastrointestinal regions raises on-target off-tumor toxicity concerns for immunotherapies 6. ROR1 expression correlates with breast cancer metastasis and reduced survival 7. Clinically, ROR1 is an emerging immunotherapeutic target in mantle cell lymphoma and solid tumors, with ROR1-targeted biologics, antibody-drug conjugates, and degrader-antibody conjugates currently in development 8910.

Sources cited
1
ROR1 is a receptor tyrosine kinase-like orphan receptor with very low kinase activity in vivo .
PMID: 25029443
2
It functions primarily as a Wnt receptor, binding WNT5A ligand to activate downstream NF-κB signaling and inhibit canonical WNT3A-mediated pathways , .
PMID: 27162350
3
ROR1 also forms complexes with ERBB2 via IGFBP5 ligand to enhance CREB oncogenic signaling .
PMID: 36949068
4
Cell surface ROR1 is expressed on ovarian, triple-negative breast, and lung adenocarcinomas, though expression on normal tissues including parathyroid, pancreatic islets, and gastrointestinal regions raises on-target off-tumor toxicity concerns for immunotherapies .
PMID: 27852699
5
ROR1 expression correlates with breast cancer metastasis and reduced survival .
PMID: 30867597
Disease Associationsⓘ21
hearing loss, autosomal recessiveOpen Targets
0.44Moderate
cervical carcinomaOpen Targets
0.36Weak
diffuse large B-cell lymphomaOpen Targets
0.36Weak
Abnormality of the skeletal systemOpen Targets
0.34Weak
smoking initiationOpen Targets
0.31Weak
thrombophiliaOpen Targets
0.29Weak
fracture of pelvisOpen Targets
0.28Weak
deafnessOpen Targets
0.27Weak
knee fractureOpen Targets
0.26Weak
septic shockOpen Targets
0.26Weak
benign neoplasmOpen Targets
0.22Weak
pneumoconiosisOpen Targets
0.22Weak
respiratory system diseaseOpen Targets
0.19Weak
chronic lymphocytic leukemiaOpen Targets
0.14Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
Mantle cell lymphomaOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
ovarian cancerOpen Targets
0.10Weak
acute lymphoblastic leukemiaOpen Targets
0.10Weak
Deafness, autosomal recessive, 108UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
CIRMTUZUMABPhase III
Inactive tyrosine-protein kinase transmembrane receptor ROR1 inhibitor
diffuse large B-cell lymphoma
Related Genes
FZD4Protein interaction100%FZD5Protein interaction100%FZD9Protein interaction100%FZD7Protein interaction100%FZD6Protein interaction100%FZD2Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Ovary
37%
Lung
29%
Brain
4%
Liver
2%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
ROR1FZD4FZD5FZD9FZD7FZD6FZD2
PROTEIN STRUCTURE
Preparing viewer…
PDB7TNG · 1.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.33Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.21 [0.14–0.33]
RankingsWhere ROR1 stands among ~20K protein-coding genes
  • #3,261of 20,598
    Most Researched141 · top quartile
  • #1,343of 17,882
    Most Constrained (LOEUF)0.33 · top 10%
Genes detectedROR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues.
PMID: 27852699
Clin Cancer Res · 2017
1.00
2
WNT signaling and cancer stemness.
PMID: 35837811
Essays Biochem · 2022
0.90
3
Therapeutic options for relapsed/refractory mantle cell lymphoma.
PMID: 34679161
Blood · 2022
0.80
4
Glucocorticoids promote breast cancer metastasis.
PMID: 30867597
Nature · 2019
0.70
5
A novel ROR1-targeting antibody-PROTAC conjugate promotes BRD4 degradation for solid tumor treatment.
PMID: 39816690
Theranostics · 2025
0.60