ROR2

receptor tyrosine kinase like orphan receptor 2, the group of Receptor tyrosine kinases|I-set domain containing

Basic information

Region (hg38): 9:91563091-91950228

Previous symbols: [ "NTRKR2", "BDB", "BDB1" ]

Links

ENSG00000169071

∙ NCBI:4920 ∙ OMIM:602337 ∙ HGNC:10257 ∙ Uniprot:Q01974 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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: CGD

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 ClinVar and linked to the ROR2 gene.

not provided (15 variants)
Autosomal recessive Robinow syndrome (5 variants)
Brachydactyly type B1 (3 variants)
Robinow syndrome, autosomal recessive, with brachy-syn-polydactyly (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			9 clinvar	131 clinvar	8 clinvar	148
missense		6 clinvar	243 clinvar	13 clinvar	11 clinvar	273
nonsense	10 clinvar	2 clinvar	1 clinvar			13
start loss						0
frameshift	6 clinvar	1 clinvar	2 clinvar			9
inframe indel			4 clinvar			4
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
splice region			4	1		5
non coding	1 clinvar		33 clinvar	49 clinvar	32 clinvar	115
Total	18	10	292	193	51

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.

Position	Phenotype	Significance	ClinVar
9-91633776-TGTACATAGGCAGAACAGGTTACTGTAACAAGTAGAGACTGCTATGGAGATTTCATTAAGGTTGACACATTCATTTCAACTGGCCAGGAGCGTCAGACCATATCCCAGAACACTCAGGCATTCTCAAGTACTAACAAATAATCCCTGTAAATCACTCACTTCCACAAAAGTTTAAAATAAAAATAGAGGTAGAGGAATCTTTCTCCAACTTTTTCCTGATGCTCTTTTCTATTCTAGTGTGATCCTGCTCTATGTTTTCCAATCTCATCATTCTTGTTCATTGCTGGTCCACTCAGTCCTTTTAAGTCAACAGTTATAAGTGTGCTTACATTCTATTAGAATGAGATCTGATGACAGGGCTTATCTAAGGCTGAAGTCCCTCAAGGACTTCCCTTCCCCAATCTCTCTCACACATCAATAAGAGCCGCAGGAGTGGCTTTATTATGTGAATTTATTGTGCCTTCTCTTGAAGAATATCATCCAATGCTGTTTTAAAATTGTATCTTTCAAATGCCATTTGAAATGGTTATAAGGCATAGAACAATATAAGCTATGGCATTTGCTAATAAGCATTAGCATGGAGCCATATGCTCCCAAAATATATTACACTTTCCACAAAGAAGTCAGAGACAGAGTTTATCAAGGATAGATACCATACTTCTTTATTCCCTAATAGCTATAGCTATATCCTTAGGGTTCTATGCTATTTTTATTTTGAAACTCTTAAATATGCAGTCTATTTCATCCCATAAACATATTAAAGACTAAATTTACCACAGGTTGTCAGACTAGAAAAAGATGAATGAGACTCTCTAAAGGCAGGCAAGCTCACTAAAAAAATATTACCCAAATGAAAACTCTGGGCAACAGAATAGTAAAGCAACACTCTTTAATGTTACTTGATCATTTGGTCACTAATTCCAGAGGATATTTGGTAAAATGTTCAACAGATAATCTGTTAAATGAGATGAAAGCCTGGGTTTGAGAAATAAAAGTGCTCTCTAAAGTTGTTTGAGTGGAAACTGTAGGGAAATAATGAGAGAGAGAGAGAGAAGAAGAAGAAGAAAAGAAGAAGAAGAAGGAGAAGGAGAAGGAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGGAGAAAAAGAAGAAAAAGAGGAGAAGAAGAAGAAGTAGCAGAGGAGGGGAGGAGGAGAAGGAAGAGGCAGAGGAGGAAGAGGCGGAGGAGGAGGAAGAGGAGGGGGAGGAAGAAGAGGAGGGGGAGGAAGAGGAGGAGGAGGAGGAGAAAGAGATTACATGCCTGTAATCCTAGCACTTTGGGAGGCCGAGGCGGGTGGACTGCCTGAGCTCAGGAGTTTGAGACCAGCCTAGGCAACACGGTGAAACCCCGTCTCTACTAAAATACAAAAAAATTAGCCGGGCATGGCGGTGTGCACCTGTAATCCCAGTTACTTGGGAGGCTGAGGCAGGAGAATTGCTTGAACCCAGGAAGCGGAGGTTGCAGTAAGCCAAGATTGCGCCATTGCACTTCAGCCTGGGCAACAGAGCAAGACTCCGTCTCAAAAAAAAAAAAAAATTGAATATTTTACCTCGTCTTAAGAGTTTCATGTCAATCTGGCCTTTATCCCTTTAAAAAGGGTCTTTCTTTTTTTTTTTTTAACTTCTCTCTGGGAGTTTCCAGAAACCTCTTTTTTCCTTTGGTGCTCATAAATTTAATGAGCATGTATATCAGTTGGGGCCATTTCTCATTCACTGCACTCAGGAATCAGCATGCCCTTTCAATAGGGGATTCATATCATTCAGCCCTGGGAATTTCCTTTAATTTTTTAAGAAATATAATTTTGGGCCAGGAGTAGCGGCTTATGCCTGTAATCCCAACACTTTGGGAGGTCGAGATAGGTGGATCACTTGAGGGCAGGAGTTCGAGACCAGCCTGGCCAACATGGCAAAACCTGTCTCTACTAAAAATACAAAAATTAGCTGGGCATGGTGGCAGGTGCCTGTGATCCCAGCTACTCAGGAGGCTGAGACAGGAGAATCCCTTGAACCCAGGAGGCGGAGGTTGCAGTGAGCCAATATCACGCCATTGCACTCCAGCCTGGGTGACAGGAGCAAAACTCCATCTCAACAAAAAATAAATAAATAAATATAATTTTGTTCTCTTAATTTTCTCTGTTCACTCTTTCTGAAAAGCCTGATGAATTGGTTTTCTATACTTCCTTTGCTTCTCTAATATTTTCCTTCTTTTTGCTCTGACTCTAAGGAGCTCATTGGATTTTCCAGGCCTTCTATTGAAATTTTTTTTAAATCCTAATTTTTCTTTATTAAAGATCTCAGTTTTTTTGTCACATTTTTGTAACATCTTGCTCTTGTTATCTAGATATGTTTCCAAAATCTCTTTTAATTCATCAATTAAGGGGATTTTTAATGTCTTCGGATTCTCTTCTTCTTTTGCTGTCAGTTTTTCTGTTGCTTGTCTTGGTTTTATGCCTTTTATATCAAGGCACATAAAAGGCATAAAACCAAGACAAGCAACAAAAAAAGGATTGATCACAGAAGTTTCTCCTTATGTGCCAATTGGTCTTCAGTTGCTCAGTTCTAGTTAAATCAAAAGACCAGGGTGGCTGGTGTGGTTTCCTCTGCTGTTGAGAACATTAGTCTGTTTTCCATCAGTCTCACCACTGAATGGGAATTCTTGCTGGATGCTCTGGGCAGGGCAGGGCATGACAGGGCAAATAGACTGGTGGGCTTTCTTTGGGTAAG-T	Normal pregnancy	not provided (-)	157151
9-91722646-A-C	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Benign (Jan 13, 2018)	367479
9-91722735-G-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign/Likely benign (Jan 12, 2018)	367480
9-91722776-C-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign (Jan 12, 2018)	367481
9-91722896-A-G	Brachydactyly • Autosomal dominant Robinow syndrome 1	Likely benign (Jun 14, 2016)	367482
9-91722926-T-C	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign/Likely benign (Jun 01, 2021)	367483
9-91722950-G-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign (May 14, 2021)	367484
9-91722980-G-C	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Uncertain significance (Jan 13, 2018)	367485
9-91723091-C-G	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Jan 13, 2018)	914694
9-91723104-G-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Jan 13, 2018)	367486
9-91723109-C-T	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Apr 27, 2017)	914695
9-91723141-C-T	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign/Likely benign (Jan 13, 2018)	367487
9-91723142-G-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Conflicting classifications of pathogenicity (Jan 13, 2018)	367488
9-91723175-G-C	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Uncertain significance (Jan 13, 2018)	367489
9-91723229-G-A	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Uncertain significance (Jan 13, 2018)	976640
9-91723264-C-G	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Jan 13, 2018)	913098
9-91723293-C-G	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Uncertain significance (Jan 12, 2018)	913099
9-91723417-T-C	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign/Likely benign (Feb 28, 2021)	367490
9-91723426-C-T		Likely benign (Dec 01, 2020)	3340920
9-91723433-G-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Benign/Likely benign (Nov 16, 2018)	367491
9-91723482-G-T	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Jan 13, 2018)	367492
9-91723486-GCTCT-G	Autosomal dominant Robinow syndrome 1 • Brachydactyly	Benign (Oct 16, 2018)	367493
9-91723527-C-A	Autosomal recessive Robinow syndrome • Brachydactyly type B1 • Brachydactyly type B1;Autosomal recessive Robinow syndrome	Uncertain significance (Jan 26, 2022)	367494
9-91723537-G-T	Autosomal recessive Robinow syndrome • Brachydactyly type B1	Uncertain significance (Jan 12, 2018)	914247
9-91723555-C-G	Brachydactyly type B1 • Autosomal recessive Robinow syndrome	Uncertain significance (Jan 13, 2018)	914248

GnomAD

Source: gnomAD

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: dbNSFP

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