DDR2

Chr 1ARAD

discoidin domain receptor tyrosine kinase 2

Also known as: DDR2-N, MIG20a, NTRKR3, TKT, TYRO10, WRCN

NCBI Gene: 4921 ENSG00000162733 UniProt: Q16832 OMIM: 191311

DDR2 encodes a receptor tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates bone development, extracellular matrix remodeling, and cell migration. Mutations cause spondylometaepiphyseal dysplasia with short limb-hand type and Warburg-Cinotti syndrome, both skeletal dysplasias affecting bone and cartilage development. The gene shows both autosomal recessive and autosomal dominant inheritance patterns and is highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the discoidin domain receptor subclass of the receptor tyrosine kinase (RTKs) protein family. RTKs play a key role in the communication of cells with their microenvironment. The encoded protein is a collagen-induced receptor that activates signal transduction pathways involved in cell adhesion, proliferation, and extracellular matrix remodeling. This protein is expressed in numerous cell types and may alos be involved in wound repair and regulate tumor growth and invasiveness. Mutations in this gene are the cause of short limb-hand type spondylometaepiphyseal dysplasia. [provided by RefSeq, Aug 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spondylometaepiphyseal dysplasia, short limb-hand typeMIM #271665

Warburg-Cinotti syndromeMIM #618175

UniProtSpondyloepimetaphyseal dysplasia, short limb-hand type

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.38

LOEUF

GOF

Mechanism· predicted

📖

GeneReview available — DDR2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.550

Z-score 4.70

OE 0.22 (0.13–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.29Z-score

OE missense 0.70 (0.64–0.77)

324 obs / 462.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.13–0.38)

0≤0.351.4

Missense OE?0.70 (0.64–0.77)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 9 / 41.8Missense obs/exp: 324 / 462.4Syn Z: -0.87

Background carrier burden — how many people carry a rare variant somewhere in DDR2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

834 rare PASS variants

Rare truncating (LoF)

1 in 4,200

61 rare PASS variants

Rare synonymous (reference)

1 in 98

403 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DDR2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 99	1 in 5,100
South Asian	~43k	1 in 66	1 in 990
Remaining (unassigned)	~30k	1 in 73	1 in 6,000
European (Finnish)	~27k	1 in 440	1 in 4,400
Admixed American	~22k	1 in 83	1 in 3,200
African / African American	~21k	1 in 100	≈ 1 in 6,400
East Asian	~20k	1 in 78	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 86	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓