BAX
BAX encodes BCL2 associated X, apoptosis regulator (192 aa). Plays a role in the mitochondrial apoptotic process. Highest expression in Cells EBV-transformed lymphocytes (212.9 TPM) and Cells Cultured fibroblasts (192.8 TPM).
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the BAX gene on chromosome 19.
The BAX protein participates in tBID bound to inactive BAX pathway.
BAX is classified as a druggable target (Druggable Genome and Tumor Suppressor categories) with score 1.4.
FLT3
FLT3 encodes fms related receptor tyrosine kinase 3 (993 aa). Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Highest expression in Brain Cerebellar Hemisphere (22.5 TPM) and Brain Cerebellum (19.7 TPM).
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the FLT3 gene on chromosome 13.
The FLT3 protein participates in FLT3 A627delinsEYEYDLKWEFPRENLEFGKVLGSGAFGKVMNA, FLT3 Y591_V592insVDFREYEYDH, and FLT3 L610_E611insCSSDNEYFYVDFREYEYDLKWEFPRENL pathways.
FLT3 is classified as a druggable target (Clinically Actionable, Drug Resistance, Druggable Genome, Kinase, and Tyrosine Kinase categories) with score 1.0.
GNB1
GNB1 encodes G protein subunit beta 1 (340 aa). Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. Highest expression in Brain Frontal Cortex BA9 (395.8 TPM) and Brain Cerebellar Hemisphere (371.2 TPM).
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the GNB1 gene on chromosome 1.
The GNB1 protein participates in Partially folded GNB1 pathway.
GNB1 is classified as a druggable target (Transporter category) with score 0.0.
NBN
NBN encodes nibrin (754 aa). Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. Highest expression in Cells EBV-transformed lymphocytes (67.2 TPM) and Esophagus Muscularis (38.3 TPM).
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the NBN gene on chromosome 8.
The NBN protein participates in KPNA2 translocates NBN to the nucleus, MRN recruits LIG3:XRCC1 to MMEJ sites, and MRN and RBBP8 resect DNA DSBs in MMEJ pathways.
NBN is classified as a druggable target (Clinically Actionable, Kinase, and Tumor Suppressor categories) with score 0.0.
NUP214
NUP214 encodes nucleoporin 214 (2,090 aa). Part of the nuclear pore complex. Has a critical role in nucleocytoplasmic transport. May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex Highest expression in Testis (95.8 TPM) and Spleen (40.1 TPM).
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the NUP214 gene on chromosome 9.
NUP214 is classified as a druggable target (Clinically Actionable, Transporter, and Tumor Suppressor categories) with score 0.0.
TAL1
TAL1 function has not been fully characterized.
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the TAL1 gene on chromosome 1.
TAL2
TAL2 function has not been fully characterized.
Leukemia, acute lymphocytic, susceptibility to, 1 is associated with mutations in the TAL2 gene on chromosome 9.
Clinical Guidance
Many recurrent GNB1 variants have been associated with phenotypic variability among individuals with the same variant. Although not conclusive, the following genotype-phenotype correlations have been proposed:
Fifty-five percent of individuals with dystonia had a p.Ile80 substitution ( or ). This possible genotype-phenotype correlation was initially suggested by .
Three of the four individuals with cutaneous mastocytosis had the p.Ile80Thr variant .
A genotype-phenotype correlation between the p.Ile80Thr variant and severe axial hypotonia or hypotonic quadriplegia has been suggested .
Source: GeneReviews — "GNB1 Encephalopathy"
Penetrance
Most probands reported to date with GNB1-E whose parents have undergone molecular genetic testing have the disorder as a result of a de novo GNB1 pathogenic variant. Penetrance is expected to be 100%.
Source: GeneReviews — "GNB1 Encephalopathy"
