NBEAL2

Chr 3AR

neurobeachin like 2

Also known as: BDPLT4, GPS

The protein contains a BEACH domain and multiple WD40 domains and is involved in thrombopoiesis, specifically playing a role in the development or secretion of platelet alpha-granules that contain growth factors important for platelet biogenesis. Mutations cause gray platelet syndrome, which follows autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.32), indicating that such variants are likely pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
ARLOEUF 0.321 OMIM phenotype
Clinical SummaryNBEAL2
🧬
Gene-Disease Validity (ClinGen)
gray platelet syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 332 VUS of 500 total submissions
📖
GeneReview available — NBEAL2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.060
Z-score 8.09
OE 0.24 (0.180.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.39Z-score
OE missense 0.83 (0.800.87)
1385 obs / 1659.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.180.32)
00.351.4
Missense OE0.83 (0.800.87)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 31 / 130.9Missense obs/exp: 1385 / 1659.3Syn Z: 0.00

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic17
VUS332
Likely Benign75
Benign11
Conflicting3
5
Pathogenic
17
Likely Pathogenic
332
VUS
75
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
3
0
5
Likely Pathogenic
16
1
0
0
17
VUS
2
326
4
0
332
Likely Benign
0
8
16
51
75
Benign
1
2
6
2
11
Conflicting
3
Total213372953443

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

View in ClinVar →

Protein Context — Lollipop Plot

NBEAL2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →