ROR2 Gene: Receptor Tyrosine Kinase-Like Orphan Receptor 2
Key regulator in skeletal development and Wnt signaling; mutations cause Robinow syndrome and brachydactyly type B1.
Gene Information Card
| Symbol | ROR2 |
|---|---|
| Full Name | Receptor Tyrosine Kinase-Like Orphan Receptor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q22.31 |
| NCBI Gene ID | 4920 ncbi.nlm.nih.gov/gene/4920 |
| Ensembl ID | ENSG00000169071 |
| UniProt ID | Q01974 |
| OMIM ID | 602337 |
| HGNC ID | 10257 |
| Aliases | BDB1, NTRKR2, MGC126563, MGC126565 |
Description
ROR2 encodes a receptor tyrosine kinase-like orphan receptor that belongs to the ROR family. It is a transmembrane protein that plays a critical role in skeletal development, chondrogenesis, and Wnt signaling pathways. ROR2 acts as a receptor for Wnt5a and modulates non-canonical Wnt signaling, influencing cell polarity, migration, and differentiation. Mutations in ROR2 cause autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B1, highlighting its importance in limb and craniofacial development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Robinow syndrome, autosomal recessive | Loss-of-function mutations lead to impaired Wnt5a signaling, disrupting skeletal and craniofacial development. | OMIM 268310; ClinVar |
| Brachydactyly type B1 | Dominant-negative mutations in the cytoplasmic domain interfere with receptor function, causing limb malformations. | OMIM 113000; ClinVar |
| Spondylocostal dysostosis (rare) | Missense variants may affect protein folding and signaling, though evidence is limited. | ClinVar; literature |
| Cancer (various) | Altered ROR2 expression or mutations may contribute to tumor progression via Wnt signaling dysregulation. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 5.2 | Low |
| Skeletal Muscle | 3.1 | Low |
| Kidney | 2.8 | Low |
| Liver | 1.5 | Not detected |
| Brain | 4.0 | Low |
| Lung | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 2.0 | Low expression |
| A549 | 1.5 | Low expression |
| MCF7 | 3.0 | Moderate expression |
| HepG2 | 1.0 | Very low expression |
| K562 | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2246G>A (p.Arg749His) | Missense | Rare | Dominant-negative effect; associated with brachydactyly type B1 |
| c.1573C>T (p.Arg525Ter) | Nonsense | Rare | Loss-of-function; causes Robinow syndrome |
| c.2224C>T (p.Arg742Cys) | Missense | Rare | Dominant-negative; brachydactyly type B1 |
| c.1195C>T (p.Arg399Ter) | Nonsense | Rare | Loss-of-function; Robinow syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein lead to haploinsufficiency or complete loss of receptor function, impairing Wnt5a signaling and causing recessive Robinow syndrome.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; ROR2 is primarily implicated in loss-of-function or dominant-negative mechanisms.
Dominant Negative (DN)
Missense mutations in the cytoplasmic domain (e.g., Arg749His) produce receptors that dimerize with wild-type ROR2 and interfere with downstream signaling, leading to dominant brachydactyly type B1.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity | • transmembrane receptor protein tyrosine kinase activity |
| • protein tyrosine kinase activity | • ATP binding |
| • Wnt-protein binding | • plasma membrane |
| • integral component of membrane | • cell surface receptor signaling pathway |
| • canonical Wnt signaling pathway | • non-canonical Wnt signaling pathway |
| • cell differentiation | • skeletal system development |
| • chondrocyte differentiation | • cell migration |
| • positive regulation of cell proliferation |
Pathways
• Wnt signaling pathway (non-canonical)
• Planar cell polarity pathway
• ROR2-mediated signaling in skeletal development
• Signaling by Receptor Tyrosine Kinases
Protein Summary
ROR2 is a type I transmembrane protein of 943 amino acids with an extracellular domain containing immunoglobulin-like, cysteine-rich, and kringle domains, and an intracellular tyrosine kinase domain. It functions as a receptor for Wnt5a, activating non-canonical Wnt signaling pathways that regulate cell polarity, migration, and differentiation. ROR2 is essential for skeletal and craniofacial development, and its dysregulation is linked to congenital disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ROR2 Knockout HEK293 Cell Line | EDJ-KQ328 | Human | 4920 | Details Get a Quote |
| ROR2 Knockout HeLa Cell Line | EDJ-KQ18304 | Human | 4920 | Details Get a Quote |
| ROR2 Knockout HCT 116 Cell Line | EDJ-KQ18493 | Human | 4920 | Details Get a Quote |
| ROR2 Knockout A-549 Cell Line | EDJ-KQ62520 | Human | 4920 | Details Get a Quote |
