GNB1L

Chr 22

G protein subunit beta 1 like

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

NCBI Gene: 54584 ENSG00000185838 UniProt: Q9BYB4 OMIM: 610778

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.05

Clinical Summary— GNB1L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

69 VUS of 104 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.02Z-score

OE missense 1.00 (0.90–1.11)

235 obs / 235.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.36–1.05)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 9 / 15.0Missense obs/exp: 235 / 235.9Syn Z: -0.25

This gene — mechanism propensity

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

104 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Likely Benign13

Benign13

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	68	0	0	69
Likely Benign	0	4	1	8	13
Benign	1	6	1	5	13
Conflicting	—				1
Total	2	78	2	13	96

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

View in ClinVar →

393 pathogenic / likely-pathogenic (of 411) ClinVar copy-number / structural variants overlap GNB1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →