GNB1L

Chr 22

G protein subunit beta 1 like

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

The protein acts as a critical regulator of DNA damage response signaling by specifically regulating phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins and contains 6 WD repeats that facilitate formation of multiprotein complexes. Mutations cause autosomal recessive intellectual disability with seizures and variable features including microcephaly and developmental delay. The gene is not highly constrained against loss-of-function variants and maps to chromosome 22q11, a region associated with DiGeorge syndrome when deleted.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.05
Clinical SummaryGNB1L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.000
Z-score 1.43
OE 0.60 (0.361.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.02Z-score
OE missense 1.00 (0.901.11)
235 obs / 235.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.361.05)
00.351.4
Missense OE1.00 (0.901.11)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 9 / 15.0Missense obs/exp: 235 / 235.9Syn Z: -0.25
DN
0.6647th %ile
GOF
0.5366th %ile
LOF
0.3550th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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