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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GNB1L
G protein subunit beta 1 like
Chromosome 22 · 22q11.21
NCBI Gene: 54584Ensembl: ENSG00000185838.15HGNC: HGNC:4397UniProt: Q9BYB4
43PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
DNA damage checkpoint signalingDNA damage responsenucleuscytoplasmopen-angle glaucomaglaucomaalcohol drinkingnephrotic syndrome
✦AI Summary

GNB1L (G protein subunit beta 1 like) is a critical regulator of DNA damage response (DDR) signaling pathways located on chromosome 22.2. Its primary function is to act as a co-chaperone that specifically regulates phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins, including ATR and ATM 12. GNB1L promotes the biogenesis of these essential DNA damage checkpoint kinases, which coordinate cellular responses to genotoxic stress and maintain genome stability 2. The gene is highly expressed in the heart 3 and operates in both cytoplasmic and nuclear compartments to regulate DNA damage checkpoint signaling 1. Clinically, GNB1L dysfunction is implicated in 22q11.2 deletion syndrome, where haploinsufficiency associates with increased schizophrenia risk—the third-highest genetic risk factor for this condition 4. Reduced GNB1L expression has been documented in schizophrenia patient prefrontal cortex 5, and missense variants affecting conserved WD40 repeat domains are associated with autism spectrum disorders 6. Additionally, GNB1L exhibits frequent copy number variations in hepatocellular carcinomas, potentially affecting cancer-associated growth signaling pathways 7. These findings establish GNB1L as central to both genome maintenance and neurodevelopmental disease pathogenesis.

Sources cited
1
GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regulating PIKK proteins
PMID: 37541219
2
GNB1L promotes biogenesis of ATR and related phosphatidylinositol 3-kinase-related kinases (PIKKs); defective PIKK biogenesis is implicated in 22q11.2 syndrome phenotypes
PMID: 37478847
3
GNB1L is highly expressed in the heart and is located in the critical region for DiGeorge syndrome on 22q11
PMID: 11072084
4
Deletion of 22q11.2 is the third highest risk for schizophrenia development; GNB1L haploinsufficiency is associated with psychosis in males with 22q11.2DS
PMID: 18636634
5
GNB1L expression is lower in postmortem prefrontal cortex of schizophrenia patients compared to controls in both Australian and Japanese populations
PMID: 19011233
6
GNB1L missense variants in WD40 repeat domains are associated with autism spectrum disorders and have predicted deleterious effects on the protein
PMID: 22095694
7
GNB1L exhibits high frequency of copy number variations (18/98 cases) in hepatocellular carcinomas
PMID: 22326833
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.15Weak
glaucomaOpen Targets
0.13Weak
alcohol drinkingOpen Targets
0.13Weak
nephrotic syndromeOpen Targets
0.07Suggestive
focal segmental glomerulosclerosisOpen Targets
0.06Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.05Suggestive
Crigler-Najjar syndrome type 2Open Targets
0.05Suggestive
nephrotic syndrome, type 24Open Targets
0.05Suggestive
congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunizationOpen Targets
0.04Suggestive
nephrotic syndrome, type 23Open Targets
0.04Suggestive
C3 glomerulonephritisOpen Targets
0.04Suggestive
Rotor syndromeOpen Targets
0.04Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.04Suggestive
immunoglobulin-mediated membranoproliferative glomerulonephritisOpen Targets
0.04Suggestive
nephrotic syndrome 15Open Targets
0.04Suggestive
neural tube defects, folate-sensitiveOpen Targets
0.04Suggestive
holoprosencephaly-hypokinesia-congenital contractures syndromeOpen Targets
0.04Suggestive
nail-patella-like renal diseaseOpen Targets
0.04Suggestive
gluthathione peroxidase deficiencyOpen Targets
0.04Suggestive
familial juvenile hyperuricemic nephropathy type 2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SEPTIN5Protein interaction90%DGCR8Protein interaction89%GP1BBProtein interaction87%GSC2Protein interaction81%TBX1Protein interaction81%RANBP1Protein interaction81%
Tissue Expression6 tissues
Ovary
100%
Lung
99%
Liver
79%
Brain
72%
Bone Marrow
42%
Heart
23%
Gene Interaction Network
Click a node to explore
GNB1LSEPTIN5DGCR8GP1BBGSC2TBX1RANBP1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BYB4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.02LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.52–1.02]
RankingsWhere GNB1L stands among ~20K protein-coding genes
  • #9,733of 20,598
    Most Researched43
  • #10,007of 17,882
    Most Constrained (LOEUF)1.02
Genes detectedGNB1L
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.
PMID: 37541219
Mol Cell · 2023
1.00
2
Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens.
PMID: 37478847
Mol Cell · 2023
0.90
3
The schizophrenia/bipolar disorder candidate gene GNB1L is regulated in human temporal cortex by a cis-acting element located within the 3'-region.
PMID: 24831436
Neurosci Bull · 2015
0.80
4
Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.
PMID: 18636634
Dev Disabil Res Rev · 2008
0.70
5
Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation.
PMID: 22326833
Am J Pathol · 2012
0.60