ROR2
receptor tyrosine kinase like orphan receptor 2, the group of Receptor tyrosine kinases|I-set domain containing
Basic information
Region (hg38): 9:91563090-91950228
Previous symbols: [ "NTRKR2", "BDB", "BDB1" ]
Links
Phenotypes
GenCC
Source:
- autosomal recessive Robinow syndrome (Supportive), mode of inheritance: AR
- brachydactyly type B1 (Strong), mode of inheritance: AD
- autosomal recessive Robinow syndrome (Strong), mode of inheritance: AR
- autosomal recessive Robinow syndrome (Definitive), mode of inheritance: AR
- brachydactyly type B1 (Definitive), mode of inheritance: AD
- autosomal dominant Robinow syndrome 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Robinow syndrome, autosomal recessive 1 | AR | Cardiovascular | The condition can involve congenital cardiac anomalies, and awareness may allow early management | Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Renal | 10700182; 10932186; 10932187; 10986040; 12919145; 15952209; 17256787; 18831060; 19461659; 22178368; 23238279; 24932600; 24954533; 26284319; 30143665; 31617258; 32172608 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (456 variants)
- Autosomal recessive Robinow syndrome (138 variants)
- Brachydactyly type B1 (123 variants)
- Brachydactyly type B1;Autosomal recessive Robinow syndrome (49 variants)
- Inborn genetic diseases (46 variants)
- not specified (33 variants)
- Autosomal recessive Robinow syndrome;Brachydactyly type B1 (26 variants)
- Short stature (9 variants)
- ROR2-related condition (6 variants)
- Autosomal dominant Robinow syndrome 1 (3 variants)
- Brachydactyly, type B1Robinow syndrome, autosomal recessive (2 variants)
- Brachydactyly (2 variants)
- Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
- Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
- ROR2-Related Disorders (1 variants)
- Robinow syndrome, autosomal recessive, with brachy-syn-polydactyly (1 variants)
- Normal pregnancy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROR2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 104 | 121 | ||||
| missense | 195 | 14 | 224 | |||
| nonsense | 10 | 12 | ||||
| start loss | 0 | |||||
| frameshift | 8 | |||||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| splice region ? | 3 | 1 | 4 | |||
| non coding ? | 29 | 45 | 32 | 107 | ||
| Total | 17 | 10 | 239 | 163 | 49 |
Highest pathogenic variant AF is 0.0000197
Variants in ROR2
This is a list of pathogenic ClinVar variants found in the ROR2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ROR2 | protein_coding | protein_coding | ENST00000375708 | 9 | 387072 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000124 | 1.00 | 125684 | 0 | 64 | 125748 | 0.000255 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.143 | 584 | 594 | 0.983 | 0.0000427 | 6118 |
| Missense in Polyphen | 150 | 189.35 | 0.7922 | 2087 | ||
| Synonymous | -3.00 | 330 | 268 | 1.23 | 0.0000214 | 1937 |
| Loss of Function | 3.73 | 14 | 39.2 | 0.357 | 0.00000247 | 385 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000797 | 0.000781 |
| Ashkenazi Jewish | 0.000298 | 0.000298 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000493 | 0.000462 |
| European (Non-Finnish) | 0.000213 | 0.000202 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000331 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation (PubMed:17717073). In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). {ECO:0000250|UniProtKB:Q9Z138, ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:25029443}.;
- Disease
- DISEASE: Brachydactyly B1 (BDB1) [MIM:113000]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type B1 the middle phalanges are short but in addition the terminal phalanges are rudimentary or absent. Both fingers and toes are affected. The thumbs and big toes are usually deformed. Symphalangism is also a feature. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Robinow syndrome autosomal recessive (RRS) [MIM:268310]: A recessive form of Robinow syndrome, a disease characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally far more severe in recessive cases, particularly skeletal abnormalities. All patients with the recessive form suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form. Patients can also present brachydactyly, with extensive aplasia/hypoplasia of the phalanges and metacarpals/metatarsals, and brachy-syn-polydactyly of the hands and oligodactyly of the feet. {ECO:0000269|PubMed:10932186, ECO:0000269|PubMed:10932187}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- WNT-Ncore;TGF-Ncore;Cardiac Progenitor Differentiation;Ectoderm Differentiation;Wnt Signaling Pathway;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;WNT5A-dependent internalization of FZD2, FZD5 and ROR2;PCP/CE pathway;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;Wnt;Wnt signaling network
(Consensus)
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- loftool
- 0.0625
- rvis_EVS
- -1.07
- rvis_percentile_EVS
- 7.35
Haploinsufficiency Scores
- pHI
- 0.188
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.546
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.947
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ror2
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype;
Zebrafish Information Network
- Gene name
- ror2
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- cartilage condensation;somitogenesis;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;Wnt signaling pathway, calcium modulating pathway;smoothened signaling pathway;JNK cascade;multicellular organism development;negative regulation of cell population proliferation;astrocyte development;peptidyl-tyrosine phosphorylation;bone mineralization;positive regulation of cell migration;BMP signaling pathway;embryonic genitalia morphogenesis;male genitalia development;inner ear morphogenesis;embryonic digit morphogenesis;positive regulation of JUN kinase activity;cell fate commitment;positive regulation of macrophage differentiation;positive regulation of transcription, DNA-templated;anatomical structure development;positive regulation of synaptic transmission, glutamatergic;Wnt signaling pathway, planar cell polarity pathway;SMAD protein signal transduction;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of protein kinase C activity;macrophage migration
- Cellular component
- microtubule;plasma membrane;integral component of plasma membrane;cell surface;axon;dendrite;clathrin-coated endocytic vesicle membrane;neuronal cell body;receptor complex
- Molecular function
- transmembrane receptor protein tyrosine kinase activity;frizzled binding;protein binding;ATP binding;Wnt-protein binding;mitogen-activated protein kinase kinase kinase binding;metal ion binding;coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway