GNB1L

Chr 22

G protein subunit beta 1 like

Also known as: DGCRK3, FKSG1, GY2, WDR14, WDVCF

NCBI Gene: 54584ENSG00000185838UniProt: Q9BYB4

This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

492
ClinVar variants
379
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GNB1L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
379 Pathogenic / Likely Pathogenic· 85 VUS of 492 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.05LOEUF
pLI 0.000
Z-score 1.43
OE 0.60 (0.36–1.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.02Z-score
OE missense 1.00 (0.90–1.11)
235 obs / 235.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.36–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.90–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 9 / 15.0Missense obs/exp: 235 / 235.9Syn Z: -0.25

ClinVar Variant Classifications

492 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic369
Likely Pathogenic10
VUS85
Likely Benign13
Benign14
Conflicting1
369
Pathogenic
10
Likely Pathogenic
85
VUS
13
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
369
0
369
Likely Pathogenic
0
0
10
0
10
VUS
1
68
16
0
85
Likely Benign
0
4
1
8
13
Benign
0
6
3
5
14
Conflicting
—1
Total17839913492

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

View in ClinVar →

Protein Context — Lollipop Plot

GNB1L · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.
Prasad SE et al.·Dev Disabil Res Rev
2008Review
Evidence for involvement of GNB1L in autism.
Chen YZ et al.·Am J Med Genet B Neuropsychiatr Genet
2012Case report
Sequencing of the coding regions of GNBIL on chromosome 22q11.2 as a risk gene of schizophrenia.
Wang YY et al.·Psychiatry Res
2021
The schizophrenia/bipolar disorder candidate gene GNB1L is regulated in human temporal cortex by a cis-acting element located within the 3'-region.
Sun Y et al.·Neurosci Bull
2015
Analysis of risk allele frequencies of single nucleotide polymorphisms related to open-angle glaucoma in different ethnic groups.
Shin HT et al.·BMC Med Genomics
2021
Chromosome 22q11.2 deletion syndrome: prenatal diagnosis, array comparative genomic hybridization characterization using uncultured amniocytes and literature review.
Chen CP et al.·Gene
2013Review
Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.
Paylor R et al.·Proc Natl Acad Sci U S A
2006
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools