NRP2

Chr 2

neuropilin 2

Also known as: NP2, NPN2, PRO2714, VEGF165R2

NCBI Gene: 8828ENSG00000118257UniProt: Q99435

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]

402
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NRP2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 200 VUS of 402 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.47LOEUF
pLI 0.001
Z-score 4.47
OE 0.31 (0.20–0.47)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.18Z-score
OE missense 0.86 (0.80–0.93)
472 obs / 549.9 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.0.31 (0.20–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.93)
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.1.04
0≤1.21.6
LoF obs/exp: 15 / 48.6Missense obs/exp: 472 / 549.9Syn Z: -0.51

ClinVar Variant Classifications

402 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic2
VUS200
Likely Benign158
Benign16
Conflicting1
25
Pathogenic
2
Likely Pathogenic
200
VUS
158
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
1
0
1
0
2
VUS
4
190
6
0
200
Likely Benign
0
24
34
100
158
Benign
1
3
2
10
16
Conflicting
—1
Total621768110402

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NRP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NEUROPILIN 2; NRP2
MIM #602070 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Human cytomegalovirus: pathogenesis, prevention, and treatment.
Shang Z et al.·Mol Biomed
2024Review
Single-cell transcriptomic profiles in the pathophysiology within the microenvironment of early diabetic kidney disease.
Tsai YC et al.·Cell Death Dis
2023
Semaphorin 3C exacerbates liver fibrosis.
De Angelis Rigotti F et al.·Hepatology
2023
A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis.
Nangle LA et al.·Sci Transl Med
2025
Therapeutic blocking of VEGF binding to neuropilin-2 diminishes PD-L1 expression to activate antitumor immunity in prostate cancer.
Wang M et al.·Sci Transl Med
2023
The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.
Moragas N et al.·Breast Cancer Res
2024
Semaphorins and its receptors: Emerging cellular biomarkers and therapeutic targets in autoimmune and inflammatory disorders.
Qamar T et al.·Life Sci
2025Review
CAF promotes chemoresistance through NRP2 in gastric cancer.
Yang Y et al.·Gastric Cancer
2022
Dual faces of angiogenesis: Mechanisms and therapeutic applications.
Izadpanah R et al.·Biochim Biophys Acta Rev Cancer
2025Review
Hypoxic migrasomes drive colorectal cancer liver metastasis by mediating CD5L(+) macrophage efferocytosis via NRP2/PROX1 axis.
Luo Y et al.·J Transl Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools