KDR

kinase insert domain receptor, the group of V-set domain containing|CD molecules|Receptor tyrosine kinases|I-set domain containing

Basic information

Region (hg38): 4:55078480-55125595

Links

ENSG00000128052 ∙ NCBI:3791 ∙ OMIM:191306 ∙ HGNC:6307 ∙ Uniprot:P35968 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pulmonary arterial hypertension (Definitive), mode of inheritance: AD

ClinVar

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

• not provided (34 variants)
• Inborn genetic diseases (28 variants)
• not specified (21 variants)
• Capillary infantile hemangioma (2 variants)
• Tufted angioma of skin (2 variants)
• Premature ovarian failure (1 variants)
• High myopia (1 variants)
• Hirschsprung disease, susceptibility to, 1 (1 variants)
• Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDR 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				6	9	15
missense		1	29	9	4	43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2		1	3
non coding					1	1
Total	0	1	30	15	14

Highest pathogenic variant AF is 0.00000657

Variants in KDR

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

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

Position	Type	Phenotype	Significance	ClinVar
4-55080002-C-T		not specified	Uncertain significance (Oct 12, 2021)
4-55080024-T-A		KDR-related disorder	Benign (Sep 10, 2019)
4-55080079-G-A		KDR-related disorder	Likely benign (Apr 25, 2019)
4-55080124-A-T		KDR-related disorder	Likely benign (Aug 19, 2019)
4-55080140-C-A			Uncertain significance (Mar 01, 2022)
4-55080156-C-G		not specified	Uncertain significance (Jan 17, 2024)
4-55080163-A-T		KDR-related disorder	Likely benign (Nov 12, 2019)
4-55081941-A-G		Capillary infantile hemangioma • not specified	Benign (-)
4-55081987-C-G		not specified	Uncertain significance (Jun 21, 2021)
4-55081996-T-G		not specified	not provided (Sep 19, 2013)
4-55082014-G-A		not specified	Uncertain significance (Jan 26, 2023)
4-55082031-G-A		Teratoma	Uncertain significance (Jan 01, 2023)
4-55082612-C-T		not specified	Uncertain significance (Dec 01, 2022)
4-55082630-T-C		not specified	Uncertain significance (Dec 17, 2023)
4-55082635-A-G		Capillary infantile hemangioma	Uncertain significance (Aug 20, 2023)
4-55088858-G-A		KDR-related disorder	Likely benign (Mar 25, 2019)
4-55088882-C-T		not specified	Uncertain significance (Sep 07, 2022)
4-55088891-G-A		Carcinoma of colon	Uncertain significance (Jan 24, 2015)
4-55088903-G-A		not specified	Uncertain significance (Apr 06, 2022)
4-55088913-C-T		Carcinoma of colon	Uncertain significance (Jan 24, 2015)
4-55088922-C-T		KDR-related disorder	Likely benign (Aug 15, 2019)
4-55088933-G-C			Uncertain significance (-)
4-55088937-G-C		Carcinoma of colon	Uncertain significance (Jan 24, 2015)
4-55088939-G-A		Capillary infantile hemangioma • not specified	Pathogenic (Mar 01, 2002)
4-55088977-G-A		Carcinoma of colon	Uncertain significance (Jan 24, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDR	protein_coding	protein_coding	ENST00000263923	30	47113

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000185	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	659	738	0.894	0.0000403	8905
Missense in Polyphen		178	282.33	0.63048		3473
Synonymous	-1.59	313	279	1.12	0.0000168	2594
Loss of Function	6.73	11	73.0	0.151	0.00000387	871

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000203	0.000203
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}.
• Disease: DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:11807987, ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18931684}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Pathway_PA165959425;Sorafenib Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;VEGF Signaling Pathway;Bevacizumab Action Pathway;Vatalanib Action Pathway;Angiogenesis;Angiogenesis overview;Cardiac Progenitor Differentiation;Nifedipine Activity;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Robo4 and VEGF Signaling Pathways Crosstalk;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Ras Signaling;Signal Transduction;vegf hypoxia and angiogenesis;VEGFA-VEGFR2 Pathway;Integrin cell surface interactions;Extracellular matrix organization;Neurophilin interactions with VEGF and VEGFR;HIF-2-alpha transcription factor network;actions of nitric oxide in the heart;VEGF ligand-receptor interactions;IL-7 signaling;Beta3 integrin cell surface interactions;SHP2 signaling;Signaling events mediated by TCPTP;JAK STAT pathway and regulation;EPO signaling;VEGF binds to VEGFR leading to receptor dimerization;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;VEGF;Notch-mediated HES/HEY network;VEGF and VEGFR signaling network;S1P1 pathway;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis;VEGFR2 mediated cell proliferation (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.196
• rvis_EVS: -1.14
• rvis_percentile_EVS: 6.39

Haploinsufficiency Scores

• pHI: 0.444
• hipred: Y
• hipred_score: 0.747
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdr
• Phenotype: 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); skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; embryo 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); normal phenotype; 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); 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); hematopoietic system phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: kdr
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: angiogenesis;vasculogenesis;positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;sprouting angiogenesis;cell migration involved in sprouting angiogenesis;endothelium development;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cell population proliferation;regulation of cell shape;positive regulation of endothelial cell migration;negative regulation of gene expression;positive regulation of phosphatidylinositol 3-kinase signaling;viral process;positive regulation of macroautophagy;cell migration;peptidyl-tyrosine phosphorylation;extracellular matrix organization;positive regulation of cell migration;embryonic hemopoiesis;calcium-mediated signaling using intracellular calcium source;cellular response to vascular endothelial growth factor stimulus;positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway;peptidyl-tyrosine autophosphorylation;negative regulation of apoptotic process;positive regulation of MAPK cascade;protein kinase B signaling;positive regulation of blood vessel endothelial cell migration;endothelial cell differentiation;positive regulation of angiogenesis;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;positive regulation of positive chemotaxis;positive regulation of nitric-oxide synthase biosynthetic process;positive regulation of focal adhesion assembly;positive regulation of mitochondrial depolarization;ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;positive regulation of cell migration involved in sprouting angiogenesis;positive regulation of mitochondrial fission;cellular response to hydrogen sulfide;negative regulation of endothelial cell apoptotic process;positive regulation of vasculogenesis
• Cellular component: extracellular region;nucleus;endosome;early endosome;endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;cell junction;receptor complex;membrane raft;sorting endosome
• Molecular function: protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;vascular endothelial growth factor-activated receptor activity;integrin binding;protein binding;ATP binding;growth factor binding;vascular endothelial growth factor binding;identical protein binding;Hsp90 protein binding