KDR

Chr 4AD

kinase insert domain receptor

KDR encodes a tyrosine kinase receptor that mediates vascular endothelial growth factor signaling, promoting endothelial cell proliferation, survival, migration, and angiogenesis during vascular development. Mutations cause infantile capillary hemangiomas with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause severe developmental consequences.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismADLOEUF 0.252 OMIM phenotypes
Clinical SummaryKDR
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Gene-Disease Validity (ClinGen)
pulmonary arterial hypertension · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 1.000
Z-score 6.73
OE 0.15 (0.090.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.03Z-score
OE missense 0.89 (0.840.95)
659 obs / 737.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.090.25)
00.351.4
Missense OE0.89 (0.840.95)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 11 / 73.0Missense obs/exp: 659 / 737.5Syn Z: -1.59
DN
0.5477th %ile
GOF
0.6833th %ile
LOF
0.54top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.25
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

LOFLoss-of-function variants in FLT4 and KDR contribute substantially to the genetic basis of TOF.PMID:30232381

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KDR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Adding the Immunotherapy Drug Cemiplimab to Usual Treatment for People With Advanced Non-Small Cell Lung Cancer Who Had Previous Treatment With Platinum Chemotherapy and Immunotherapy (An Expanded Lung-MAP Treatment Trial)

RECRUITING
NCT06616584Phase PHASE2, PHASE3SWOG Cancer Research NetworkStarted 2025-05-22
Biospecimen CollectionCemiplimabComputed Tomography
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING
NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23
OlaparibDasatinibNivolumab plus Ipilimumab
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Ramucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study

ACTIVE NOT RECRUITING
NCT05633602Phase PHASE3SWOG Cancer Research NetworkStarted 2023-03-14
ChemotherapyPembrolizumabRamucirumab
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)

RECRUITING
NCT06031688Phase PHASE2SWOG Cancer Research NetworkStarted 2024-08-08
Biospecimen CollectionComputed TomographyLymphoscintigraphy
BRCA-Mutated Breast CarcinomaHER2-negative Breast Cancer

Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab

RECRUITING
NCT06516289Phase PHASE2Fudan UniversityStarted 2024-09-30
HRS-1167FamitinibCamrelizumab
Lung CancerTKI ResistanceEGFR Sensitive Mutation

A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody

NOT YET RECRUITING
NCT06048315Phase PHASE3Degan LuStarted 2023-09
AnlotinibPenpulimab
Coronary Disease

Genetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response

ACTIVE NOT RECRUITING
NCT03373552Hôpital Universitaire Fattouma BourguibaStarted 2015-08-12
Platelet function assay
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Comparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)

RECRUITING
NCT05642572Phase PHASE2SWOG Cancer Research NetworkStarted 2023-05-05
Biospecimen CollectionCapmatinibComputed Tomography
Advanced Solid Tumors

Safety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors

ACTIVE NOT RECRUITING
NCT05914376Phase PHASE1Hangzhou Converd Co., Ltd.Started 2023-07-05
Recombinant human IL-21-expressing oncolytic vaccinia virus injection
Clinical Literature
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