KDR

Chr 4AD

kinase insert domain receptor

Also known as: CD309, FLK1, VEGFR, VEGFR2

NCBI Gene: 3791 ENSG00000128052 UniProt: P35968

Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

Primary Disease Associations & Inheritance

{Hemangioma, capillary infantile, susceptibility to}MIM #602089

Hemangioma, capillary infantile, somaticMIM #602089

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

1.0

Missense Z

0.25

LOEUF· LoF intolerant

Clinical Summary— KDR

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Gene-Disease Validity (ClinGen)

pulmonary arterial hypertension · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

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.

0.25LOEUF

pLI 1.000

Z-score 6.73

OE 0.15 (0.09–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% 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.

1.03Z-score

OE missense 0.89 (0.84–0.95)

659 obs / 737.5 exp

Tolerant

Mild missense constraint

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.0.15 (0.09–0.25)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.84–0.95)

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.1.12

0≤1.21.6

LoF obs/exp: 11 / 73.0Missense obs/exp: 659 / 737.5Syn Z: -1.59

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

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

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

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

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

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

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

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

Clinical Literature

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3