NRP2

protein-coding

neuropilin 2

Gene summary

This gene encodes a member of the neuropilin family of receptor proteins. The encoded transmembrane protein binds to SEMA3C protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C} and SEMA3F protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F}, and interacts with vascular endothelial growth factor (VEGF). This protein may play a role in cardiovascular development, axon guidance, and tumorigenesis. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Jul 2021]

MANE transcript

NM_003872.3

Inheritance

—

ClinVar variants

P:1U:279B:159

Top phenotype

NRP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr2:205,681,990-205,798,133

External References & Databases

Ensembl (ENSG00000118257)

Transcript & Mutation Effects

hg38 • Region Span ~116.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NRP2 variants in ClinVar

5 Conditions Cataloged

NRP2-related disorderTotal: 466

not specifiedTotal: 104

not providedTotal: 33

Hirschsprung disease, susceptibility to, 1Total: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003872.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	122 clinvar	7 clinvar	133
missense			262 clinvar	27 clinvar	3 clinvar	292
nonsense			4 clinvar			4
start loss			1 clinvar			1
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	279	149	10	439

Highest pathogenic variant AF is 0.000004336739

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003872.3	RefSeq	NP_003863.2	17	MANE Select
ENST00000357785.10	Ensembl	ENSP00000350432.5	17	MANE Select
NM_018534.4	RefSeq	NP_061004.3	16	Standard
NM_201264.2	RefSeq	NP_957716.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nrp2b	Danio rerio	Structure: cranial neural crest Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

nrp2b

Danio rerio

Structure: cranial neural crest

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

VEGFA-VEGFR2 Signaling Pathway
EMT transition in Colorectal Cancer
Developmental Biology
Signal Transduction
Neurophilin interactions with VEGF and VEGFR

Biological Process

angiogenesis
positive regulation of endothelial cell proliferation
outflow tract septum morphogenesis
cell adhesion
axon guidance

Molecular Function

vascular endothelial growth factor-activated receptor activity
protein binding
heparin binding
semaphorin receptor activity
growth factor binding

Cellular Component

semaphorin receptor complex
extracellular region
plasma membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360409
Coding exons: 17
Length: 116144
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.18	472	550	0.858	0.0000347	6126
Missense (PolyPhen)		199	273.56	0.72744		3035
Synonymous	-0.510	236	226	1.04	0.0000157	1806
Loss of Function	4.47	15	48.6	0.308	0.00000242	525

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.;

Recessive Scores

pRec: 0.151

Intolerance Scores

LoFtool: 0.0247
RVIS EVS: -1.08
RVIS percentile EVS: 7.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.986

Gene Damage Prediction

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