DDR2

discoidin domain receptor tyrosine kinase 2, the group of Receptor tyrosine kinases

Basic information

Region (hg38): 1:162631373-162787405

Previous symbols: [ "TYRO10", "NTRKR3" ]

Links

ENSG00000162733 ∙ NCBI:4921 ∙ OMIM:191311 ∙ HGNC:2731 ∙ Uniprot:Q16832 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Definitive), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Moderate), mode of inheritance: AR
• warburg-cinotti syndrome (Limited), mode of inheritance: AD
• warburg-cinotti syndrome (Limited), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Supportive), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Strong), mode of inheritance: AR
• warburg-cinotti syndrome (Limited), mode of inheritance: Unknown
• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Definitive), mode of inheritance: AR
• warburg-cinotti syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warburg-Cinotti syndrome	AD	Dermatologic; Ophthalmologic	It has been suggested that DDR2-inhibition (eg, via dasatinib), could be used for treatment of affected individuals	Craniofacial; Dermatologic; Musculoskeletal; Ophthalmologic	8434618; 19110212; 17103436; 20223752; 23637089; 30449416

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDR2 gene.

• not provided (10 variants)
• Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDR2 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			4	59	4	67
missense	1	1	122	3		127
nonsense	6		2			8
start loss			1			1
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			3	4		7
non coding			16	50	30	96
Total	10	4	145	112	34

Highest pathogenic variant AF is 0.0000329

Variants in DDR2

This is a list of pathogenic ClinVar variants found in the DDR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-162632505-C-T		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 13, 2018)
1-162632565-G-A		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 12, 2018)
1-162632576-G-A		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 13, 2018)
1-162632602-C-T		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Mar 16, 2018)
1-162632604-T-C		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 13, 2018)
1-162655296-G-T		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 13, 2018)
1-162718831-A-G			Benign (Nov 20, 2018)
1-162718844-T-C			Likely benign (Dec 11, 2019)
1-162718891-G-A			Likely benign (Dec 05, 2018)
1-162719019-A-G			Likely benign (Jul 30, 2019)
1-162719026-G-C		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (Jan 13, 2018)
1-162719065-T-G		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Uncertain significance (May 12, 2022)
1-162719091-G-A			Uncertain significance (May 05, 2022)
1-162719120-T-C			Likely benign (Jun 20, 2023)
1-162719142-C-T			Uncertain significance (Jun 27, 2022)
1-162719154-G-A			Likely benign (Aug 20, 2022)
1-162752860-C-T			Likely benign (Mar 03, 2019)
1-162752966-A-G			Likely benign (Dec 29, 2019)
1-162753056-C-G		not specified • Warburg-cinotti syndrome • Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Benign (Jul 30, 2021)
1-162753078-G-C			Likely benign (Aug 23, 2022)
1-162753080-T-A			Likely benign (Feb 18, 2023)
1-162753091-C-T		Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome • Connective tissue disorder	Benign/Likely benign (Jan 23, 2024)
1-162753097-A-C			Uncertain significance (Jan 20, 2020)
1-162753097-A-G		Inborn genetic diseases	Likely benign (Mar 14, 2023)
1-162753103-C-T			Uncertain significance (Jul 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDR2	protein_coding	protein_coding	ENST00000367922	16	156028

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.550	0.450	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.29	324	462	0.701	0.0000267	5652
Missense in Polyphen		97	194.92	0.49764		2394
Synonymous	-0.874	183	169	1.09	0.00000939	1635
Loss of Function	4.70	9	41.8	0.215	0.00000242	466

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000892	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:9659899}.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short- limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. {ECO:0000269|PubMed:19110212, ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:26463668}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endochondral Ossification;Extracellular matrix organization;Non-integrin membrane-ECM interactions (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.0426
• rvis_EVS: -0.78
• rvis_percentile_EVS: 13.05

Haploinsufficiency Scores

• pHI: 0.850
• hipred: Y
• hipred_score: 0.824
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ddr2
• Phenotype: craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism 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; 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; growth/size/body region 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; 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; skeleton phenotype; neoplasm

Gene ontology

• Biological process: ossification;regulation of cell-matrix adhesion;endochondral bone growth;cell adhesion;cell-matrix adhesion;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cell population proliferation;regulation of extracellular matrix disassembly;positive regulation of fibroblast migration;peptidyl-tyrosine phosphorylation;cell differentiation;extracellular matrix organization;collagen fibril organization;regulation of bone mineralization;biomineral tissue development;chondrocyte proliferation;collagen-activated tyrosine kinase receptor signaling pathway;positive regulation of osteoblast differentiation;positive regulation of protein kinase activity;protein autophosphorylation;positive regulation of fibroblast proliferation;positive regulation of DNA-binding transcription factor activity;positive regulation of extracellular matrix disassembly;regulation of extracellular matrix organization
• Cellular component: plasma membrane;integral component of plasma membrane;focal adhesion;actin cytoskeleton;apical plasma membrane;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;protein binding;collagen binding;ATP binding;protein tyrosine kinase collagen receptor activity