NRP1

neuropilin 1, the group of CD molecules

Basic information

Region (hg38): 10:33177491-33336262

Links

ENSG00000099250 ∙ NCBI:8829 ∙ OMIM:602069 ∙ HGNC:8004 ∙ Uniprot:O14786 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRP1 gene.

• Inborn genetic diseases (32 variants)
• NRP1-related condition (28 variants)
• not provided (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRP1 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			1	1	2	4
missense			54	5	2	61
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding					1	1
Total	0	0	55	6	5

Variants in NRP1

This is a list of pathogenic ClinVar variants found in the NRP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-33180070-C-T		NRP1-related disorder	Likely benign (Aug 09, 2021)
10-33180086-G-A		not specified	Uncertain significance (Jul 14, 2023)
10-33180152-T-C		NRP1-related disorder	Uncertain significance (May 03, 2023)
10-33180159-C-G		not specified	Uncertain significance (Oct 28, 2023)
10-33180203-G-T		not specified	Uncertain significance (Apr 13, 2023)
10-33180216-C-T		NRP1-related disorder	Uncertain significance (Feb 13, 2024)
10-33180217-G-T		NRP1-related disorder	Benign (Nov 11, 2019)
10-33180219-C-A		not specified	Uncertain significance (Jun 23, 2023)
10-33180253-A-G		NRP1-related disorder	Benign (Oct 21, 2019)
10-33180277-G-C		NRP1-related disorder	Uncertain significance (Dec 05, 2023)
10-33180286-T-C		NRP1-related disorder	Likely benign (Dec 18, 2023)
10-33180326-T-C		not specified	Uncertain significance (May 23, 2023)
10-33180330-C-T		not specified	Uncertain significance (Mar 17, 2023)
10-33180346-T-A		not specified	Uncertain significance (Jun 06, 2023)
10-33180348-C-T		NRP1-related disorder	Benign/Likely benign (Feb 01, 2024)
10-33180358-C-T		NRP1-related disorder	Benign (Feb 25, 2019)
10-33180368-A-G		NRP1-related disorder	Likely benign (May 19, 2021)
10-33182704-C-T		not specified	Uncertain significance (Dec 31, 2023)
10-33182707-C-G		not specified	Uncertain significance (Feb 13, 2024)
10-33182709-A-G		NRP1-related disorder • not specified	Conflicting classifications of pathogenicity (Oct 05, 2021)
10-33185625-T-C		NRP1-related disorder	Likely benign (Mar 01, 2023)
10-33185704-G-A		NRP1-related disorder	Likely benign (Dec 13, 2021)
10-33185710-G-A		NRP1-related disorder	Likely benign (Jan 05, 2023)
10-33185710-G-T		NRP1-related disorder	Benign/Likely benign (Dec 31, 2019)
10-33185716-G-A		NRP1-related disorder	Benign (Mar 22, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRP1	protein_coding	protein_coding	ENST00000265371	17	158771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.986	0.0142	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	434	536	0.810	0.0000293	6089
Missense in Polyphen		160	243.3	0.65762		2666
Synonymous	-0.325	206	200	1.03	0.0000121	1731
Loss of Function	5.36	8	48.2	0.166	0.00000263	535

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF165 isoform of VEGFA and VEGFB. Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulate VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). {ECO:0000250|UniProtKB:P97333}.
• Pathway: HTLV-I infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);VEGF Signaling Pathway;Angiogenesis overview;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Developmental Biology;Signal Transduction;Neurophilin interactions with VEGF and VEGFR;CHL1 interactions;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Sema3A PAK dependent Axon repulsion;Semaphorin interactions;Signal transduction by L1;Signaling by ROBO receptors;Signaling by VEGF;L1CAM interactions;Plexin-D1 Signaling;Axon guidance;CRMPs in Sema3A signaling;Signaling by Receptor Tyrosine Kinases;VEGF and VEGFR signaling network;VEGFR1 specific signals (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.0615
• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.75

Haploinsufficiency Scores

• pHI: 0.554
• hipred: Y
• hipred_score: 0.786
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrp1
• Phenotype: immune system 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); neoplasm; 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; 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); embryo phenotype; cellular phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: nrp1b
• Affected structure: mid cerebral vein
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: angiogenesis;branching involved in blood vessel morphogenesis;neuron migration;positive regulation of endothelial cell proliferation;sprouting angiogenesis;cell migration involved in sprouting angiogenesis;outflow tract septum morphogenesis;substrate-dependent cell migration, cell extension;signal transduction;integrin-mediated signaling pathway;cell-cell signaling;axon guidance;axonal fasciculation;response to wounding;animal organ morphogenesis;positive regulation of endothelial cell migration;positive regulation of smooth muscle cell migration;facial nerve structural organization;trigeminal nerve structural organization;vestibulocochlear nerve structural organization;nerve development;branchiomotor neuron axon guidance;gonadotrophin-releasing hormone neuronal migration to the hypothalamus;retinal ganglion cell axon guidance;actin cytoskeleton reorganization;regulation of Cdc42 protein signal transduction;substrate adhesion-dependent cell spreading;cellular response to hepatocyte growth factor stimulus;endothelial cell chemotaxis;cellular response to vascular endothelial growth factor stimulus;ventral trunk neural crest cell migration;neuropilin signaling pathway;VEGF-activated neuropilin signaling pathway;positive regulation of phosphorylation;negative regulation of neuron apoptotic process;endothelial cell migration;positive regulation of GTPase activity;platelet-derived growth factor receptor signaling pathway;vascular endothelial growth factor receptor signaling pathway;hepatocyte growth factor receptor signaling pathway;positive regulation of axon extension involved in axon guidance;negative regulation of axon extension involved in axon guidance;artery morphogenesis;axon extension involved in axon guidance;positive regulation of peptidyl-tyrosine phosphorylation;positive chemotaxis;positive regulation of filopodium assembly;positive regulation of stress fiber assembly;positive regulation of focal adhesion assembly;positive regulation of cytokine activity;axonogenesis involved in innervation;regulation of vesicle-mediated transport;dichotomous subdivision of terminal units involved in salivary gland branching;angiogenesis involved in coronary vascular morphogenesis;coronary artery morphogenesis;retina vasculature morphogenesis in camera-type eye;renal artery morphogenesis;sympathetic ganglion development;trigeminal ganglion development;positive regulation of ERK1 and ERK2 cascade;semaphorin-plexin signaling pathway;commissural neuron axon guidance;positive regulation of cell migration involved in sprouting angiogenesis;regulation of retinal ganglion cell axon guidance;endothelial tip cell fate specification;sensory neuron axon guidance;motor neuron migration;sympathetic neuron projection extension;sympathetic neuron projection guidance;postsynapse organization;basal dendrite development;basal dendrite arborization;positive regulation of substrate adhesion-dependent cell spreading;neural crest cell migration involved in autonomic nervous system development;toxin transport;semaphorin-plexin signaling pathway involved in neuron projection guidance;semaphorin-plexin signaling pathway involved in axon guidance;positive regulation of retinal ganglion cell axon guidance;VEGF-activated neuropilin signaling pathway involved in axon guidance;protein localization to early endosome;facioacoustic ganglion development;dorsal root ganglion morphogenesis;otic placode development;positive regulation of actin cytoskeleton reorganization;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: semaphorin receptor complex;extracellular space;early endosome;cytosol;neurofilament;plasma membrane;focal adhesion;cell surface;axon;growth cone;cytoplasmic vesicle;neuron projection;neuronal cell body;receptor complex;sorting endosome;glutamatergic synapse;integral component of postsynaptic membrane
• Molecular function: vascular endothelial growth factor-activated receptor activity;GTPase activator activity;protein binding;heparin binding;coreceptor activity;semaphorin receptor activity;growth factor binding;protein kinase binding;cytokine binding;vascular endothelial growth factor binding;metal ion binding