DDR1

Chr 6

discoidin domain receptor tyrosine kinase 1

Also known as: CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4

NCBI Gene: 780ENSG00000204580UniProt: Q08345

Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

128
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DDR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 105 VUS of 128 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.000
Z-score 3.74
OE 0.39 (0.27–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.22Z-score
OE missense 0.75 (0.69–0.81)
454 obs / 608.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.27–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 17 / 43.7Missense obs/exp: 454 / 608.4Syn Z: 1.85

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS105
Likely Benign16
Benign2
4
Pathogenic
1
Likely Pathogenic
105
VUS
16
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
99
6
0
105
Likely Benign
0
14
0
2
16
Benign
0
0
1
1
2
Total0113123128

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DDR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy.
Di Martino JS et al.·Nat Cancer
2022
Modulating tumor collagen fiber alignment for enhanced lung cancer immunotherapy via inhaled RNA.
Hu B et al.·Nat Commun
2025
The role of DDR1 in cancer and the progress of its selective inhibitors.
Wang J et al.·Bioorg Chem
2025Review
New target DDR1: A "double-edged sword" in solid tumors.
Tian Y et al.·Biochim Biophys Acta Rev Cancer
2023Review
Discoidin domain receptor 1 activation links extracellular matrix to podocyte lipotoxicity in Alport syndrome.
Kim JJ et al.·EBioMedicine
2021
Research progress of DDR1 inhibitors in the treatment of multiple human diseases.
Liu M et al.·Eur J Med Chem
2024Review
Role of DDR1 in Regulating MMPs in External Root Resorption.
Wang Y et al.·Int J Mol Sci
2024
Inhibition of DDR1 promotes ferroptosis and overcomes gefitinib resistance in non-small cell lung cancer.
Zhang Y et al.·Biochim Biophys Acta Mol Basis Dis
2024
DDR1 Drives Collagen Remodeling and Immune Exclusion: Pan-Cancer Insights and Therapeutic Targeting in Pancreatic Ductal Adenocarcinoma.
Huang X et al.·Int J Mol Sci
2025Functional
Functional Role of DDR1 in Oligodendrocyte Signaling Mechanism in Association with Myelination and Remyelination Process in the Central Nerve System.
Anand MAV et al.·J Physiol Investig
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Malignant Solid Neoplasms

Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment

RECRUITING
NCT02029001Phase PHASE2Centre Leon BerardStarted 2014-03
Nilotinib (400 mg BID)Everolimus (10 mg QD)Sorafenib (400 mg BID)

External Resources

Links to major genomics databases and tools