Mouse Nbeal2

Human disease models (by orthology)

Mouse phenotype associations

Nbeal2

Human ortholog NBEAL2

Gene expression

Name Neurobeachin-like 2Synonyms KIAA0540

Function Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis.

Domains and Repeats

Name Neurobeachin-like 2Synonyms 1110014F23RikMGI Id MGI:2448554

In homozygote • Both sexes have the following phenotypic

abnormalities:• skeleton phenotype• hematopoietic system phenotype

• Following phenotypic abnormalities occurred in males only

• immune system phenotype.

Hematology | Mean platelet volume

P = 0.0

Disease Name In Locus MGI IMPC

Gray Platelet Syndrome Yes 86.59 61.96Gray Platelet Syndrome Yes 70.3 55.27

Subcellular location Endoplasmic reticulum

GO Molecular Functions phospholipid binding

GO Cellular Components endomembrane system; endoplasmic reticulum; extrinsic component of membrane; membrane

GO Biological processes blood coagulation; endosomal transport; megakaryocyte development; platelet alpha granule organization; platelet formation

Protein Existence Evidence at the protein level

InteractionsNBEAL2 – glgX (two hybrid pooling approach)

Allelic Structure

Mouse phenotype association images

Knockout Lethality

Armadillo-type fold

Concanavalin A-like lectin/glucanase domain

PH-BEACH domain

BEACH domain

WD40/YVTN repeat-like-containing domain

WD40 repeat

Greater colour saturation means higher expression. Please note that expression values are not directly comparable across experiments.

FPKM/TPM (Transcriptomics) > 0.5

embryonic viable

Description NBEAL2 belongs to the BEACH (beige and CHS1) domain-containing protein family, which includes NBEAL1 (609816), neurobeachin (NBEA; 604889), CHS1 (LYST; 606897), and LRBA (606453). NBEAL2 is predicted to have a role in alpha-granule biogenesis in megakaryocytes (Gunay-Aygun et al., 2011; Albers et al., 2011; Kahr et al., 2011).

Molecular Genetics Simultaneously and independently, Gunay-Aygun et al. (2011), Albers et al. (2011), and Kahr et al. (2011) identified biallelic mutations in the NBEAL2 gene in patients with gray platelet syndrome (GPS; 139090), a rare autosomal recessive disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules...

Animal Model Albers et al. (2011) found that knockout of zebrafish Nbeal2 via morpholino oligonucleotides resulted in spontaneous tail bleeding in 41% of embryos. Morpholino knockdown resulted in complete abrogation of thrombocytes, the zebrafish equivalent of platelets, whereas mature erythrocytes were not affected.

Approved Drugs

Potential human disease models predicted by phenotypic similarity

Disease Name In Locus

Aicardi-Goutieres Syndrome 1 YesMetaphyseal Chondrodysplasia, Jansen Type YesBleeding Disorder, Platelet-Type, 15Sebastian SyndromePlatelet Glycoprotein Iv Deficiency

Nbeal2 (with extra info from other genes for illustration)

STRING Predicted Functional Partners

Reactome Pathway inferred by orthology

Or genomic context, or ChEMBL compounds list…. ?Or OMIM disease info (for orthologue associated diseases)

OMIM Information

ChEMBL Target Information

Summation p53 causes G1 arrest by inducing the expression of a cell cycle inhibitor, p21 (El-Deiry et al, 1993; Harper et al, 1993; Xiong et al, 1993). P21 binds and inactivates Cyclin-Cdk complexes that mediate G1/S progression, resulting in lack of phosphorylation of Rb, E2F sequestration and cell cycle arrest at the G1/S transition. Mice with a homozygous deletion of p21 gene are deficient in their ability to undergo a G1/S arrest in response to DNA damage (Deng et al, 1995).

Rhbdl1 rhomboid, veinlet-like 1 0.878

Brd9 bromodomain containing 9 0.649Sqstm1 sequestosome 1 0.516Tnfrsf1a tumor necrosis factor receptor superfamily, member 1a 0.494Snx17 sorting nexin 17 0.473Selp selectin, platelet 0.469Gpr128 G protein-coupled receptor 0.457Srsf9 serine/arginine-rich splicing factor 9 0.447Shank3 SH3/ankyrin domain gene 3 0.442Rabggta Rab geranylgeranyl transferase 0.416

Target associated bioactivities

Component Description cGMP-specific 3',5'-cyclic phosphodiesteraseRelationship single protein

Target RelationsChEMBL ID Pref Name Target Type

CHEMBL2363066 3',5'-cyclic phosphodiesterase

PROTEIN FAMILY

CHEMBL2111400 Phosphodiesterase 3 and 5 (PDE3 and

PDE5)

SELECTIVITY GROUP

CHEMBL2095220 Phosphodiesterases; PDE5 & PDE6

SELECTIVITY GROUP

CHEMBL2111340 Phosphodiesterase 4 and 5 (PDE4 and

PDE5)

SELECTIVITY GROUP

CHEMBL2097161 Phosphodiesterase, PDE1/PDE5

PROTEIN FAMILY

CHEMBL2111470 Phosphodiesterase 2 and 5 (PDE2 and

PDE5)

SELECTIVITY GROUP

ChEMBL ID Name Mechanism of Action

CHEMBL1963681 AVANAFIL Phosphodiesterase 5A inhibitor

CHEMBL1737 SILDENAFIL CITRATE Phosphodiesterase 5A inhibitor

CHEMBL779 TADALAFIL Phosphodiesterase 5A inhibitor

CHEMBL1339 VARDENAFIL HYDROCHLORIDE

Phosphodiesterase 5A inhibitor