PLXNB2

Chr 22

plexin B2

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

NCBI Gene: 23654 ENSG00000196576 UniProt: O15031 OMIM: 604293

PLXNB2 encodes a transmembrane receptor that binds semaphorins and angiogenin to regulate axon guidance, neuronal cell migration during brain development, and glutamatergic synapse formation. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and brain malformations, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— PLXNB2

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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.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 284 VUS of 418 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.19 (0.13–0.28)

0≤0.351.4

Missense OE?0.73 (0.69–0.77)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 17 / 89.5Missense obs/exp: 896 / 1227.5Syn Z: -3.17

ClinVar Variant Classifications

418 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

VUS284

Likely Benign59

Benign9

Pathogenic

284

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	3	0	1	8
Likely Pathogenic	0	0	0	0	0
VUS	3	281	0	0	284
Likely Benign	0	22	4	33	59
Benign	0	1	2	6	9
Total	7	307	6	40	360

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

View in ClinVar →

142 pathogenic / likely-pathogenic (of 155) ClinVar copy-number / structural variants overlap PLXNB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →