Receptor Tyrosine Kinase-Like Orphan Receptor 2

Alternative Names

  • ROR2
  • Neurotrophic Tyrosine Kinase, Receptor-Related 2
  • NTRKR2
Back to search Result
OMIM Number

602337

NCBI Gene ID

4920

Uniprot ID

Q01974

Length

387,072 bases

No. of Exons

13

No. of isoforms

1

Protein Name

Tyrosine-protein kinase transmembrane receptor ROR2

Molecular Mass

104757Da

Amino Acid Count

943

Genomic Location

chr9:91563091-91950162

Gene Map Locus
9q22.31

Description

Receptor tyrosine kinases (RTKs) are a class of cell membrane proteins, which have a high affinity for specific growth factors, hormones, and cytokines. Binding of the receptor to the specific ligand results in the activation of secondary messengers, thus, leading to a signal transduction cascade within the cell. Most RTKs function as key regulators of normal cellular processes. ROR2 (Receptor Tyrosine Kinase-Like Orphan Receptor 2) belongs to the RTK family. Like other RTKs, the ROR2 protein also consists of an extracellular region, a transmembrane section, and an intracellular structure. The extracellular region consists of an immunoglobulin-like (Ig) domain, a frizzled-like cysteine rich domain (CRD), and a kringle domain (KD), and these motifs are expected to be involved in protein-protein interactions. The intracellular region, on the other hand, contains the tyrosine kinase (TK) domain. However, it is an orphan receptor, implying that the ligand specific to it, if existent, is not known at present. Although the exact biochemical and molecular function of the ROR2 protein is not known, it is assumed that the receptor and its signaling events are involved in the early formation of chondrocytes, and that it may be required for the development of cartilages and growth plates.

The function of ROR2 is supported by its role in diseases of the skeletal system. Mutations in ROR2 are responsible for brachydactyly type B (BDB) and autosomal recessive Robinow syndrome.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_004560.3:c.814C>TLebanonChr9:91733245Robinow Syndrome, Autosomal RecessiveNG_008089.1:g.221918C>T; NM_004560.3:c.814C>T; NP_004551.2:p.Arg272Cys763809292
NM_004560.4:c.1970G>AYemenNC_000009.12:g.91724524C>TLikely Pathogenic, Uncertain SignificanceLikely PathogenicRobinow Syndrome, Autosomal RecessiveNG_008089.1:g.230639G>A; NM_004560.4:c.1970G>A; NP_004551.2:p.Arg657His529829552159813
NM_004560.4:c.574T>GEgyptNC_000009.12:g.91737439A>CPathogenicRobinow Syndrome, Autosomal RecessiveNG_008089.1:g.217724T>G; NM_004560.4:c.574T>G; NP_004551.2:p.Tyr192Asp

Other Reports

Jordan

Hamamy et al. (2006) described a Jordanian patient who was diagnosed with the severe form of Brachydactyly type B1. The ROR2 coding regions as well as the intron-exon boundaries of exons 8 and 9 were sequenced to identify the mutation responsible for the condition. The patient was found to carry a de novo distal mutation, C2265A (Y755X) in exon 9, resulting in premature termination of the protein product.

Oman

Afzal et al. (2000a) performed homozygosity mapping (also known as autozygosity mapping) in five consanguineous Omani families reported by Soliman et al. (1998). Two additional families were used to test for genetic heterogeneity and to refine the position of the locus. The results indicated that the gene lies within a 4-cM region between markers D9S1836 and D9S1803 (maximum multipoint lod score 12.3). Afzal et al. (2000b) studied 14 patients from seven families from Oman using SSCP analysis and found band shifts suggestive of homozygous changes in exon 9 of the ROR2 gene. Sequencing of the fragments identified a gln502-to-ter (Q502X) nonsense mutation in exon 9 of the ROR2 gene that removed the tyrosine kinase domain and all subsequent 3-prime regions. The nature of this mutation suggested that this form of Robinow syndrome is caused by loss of ROR2 activity. Interestingly, all the Omani cases shared a common haplotype at the locus, thus, suggestive of a single founder mutation. PCR-RFLP or SSCP analyses of 40 chromosomes from unrelated Omani individuals did not indicate the presence of the mutation.

© CAGS 2024. All rights reserved.