PLXNB2

Chr 22

plexin B2

Also known as: MM1, Nbla00445, PLEXB2, dJ402G11.3, lncFAL

NCBI Gene: 23654ENSG00000196576UniProt: O15031

Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

503
ClinVar variants
147
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PLXNB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
147 Pathogenic / Likely Pathogenic· 293 VUS of 503 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.28LOEUF
pLI 0.992
Z-score 7.10
OE 0.19 (0.13–0.28)
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.
3.36Z-score
OE missense 0.73 (0.69–0.77)
896 obs / 1227.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.19 (0.13–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.69–0.77)
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.1.17
0≤1.21.6
LoF obs/exp: 17 / 89.5Missense obs/exp: 896 / 1227.5Syn Z: -3.17

ClinVar Variant Classifications

503 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic146
Likely Pathogenic1
VUS293
Likely Benign52
Benign11
146
Pathogenic
1
Likely Pathogenic
293
VUS
52
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
3
139
1
146
Likely Pathogenic
0
0
1
0
1
VUS
2
279
12
0
293
Likely Benign
0
22
3
27
52
Benign
0
1
4
6
11
Total530515934503

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

View in ClinVar →

Protein Context — Lollipop Plot

PLXNB2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PLXNB2-related hearing loss, amelogenesis imperfecta and intellectual disability

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. DisordersEar
G2P ↗
splice region variantframeshift variantstop gainedmissense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PLEXIN B2; PLXNB2
MIM #604293 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia.
Guo Z et al.·Mol Biol Rep
2023
Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability.
Smith CEL et al.·J Med Genet
2024
Evidence for common mechanisms of pathology between SHANK3 and other genes of Phelan-McDermid syndrome.
Mitz AR et al.·Clin Genet
2024Review
A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia.
Lin L et al.·J Transl Med
2021Cohort
Protein profiles and associated biological pathways among different aetiologies of chronic kidney disease: new insights from DAPA-CKD.
de la Rambelje MA et al.·Nephrol Dial Transplant
2026
Whole exome sequencing in unexplained recurrent miscarriage families identified novel pathogenic genetic causes of euploid miscarriage.
Wang X et al.·Hum Reprod
2023
Potential Immune Biomarker Candidates and Immune Subtypes of Lung Adenocarcinoma for Developing mRNA Vaccines.
Wang Y et al.·Front Immunol
2021
Genetics of kidney disorders in Phelan-McDermid syndrome: evidence from 357 registry participants.
McCoy MD et al.·Pediatr Nephrol
2024
Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression.
Yin J et al.·Genes (Basel)
2020
Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma.
Zhao L et al.·Hepatol Int
2022Functional
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