RABGGTB

Chr 1

Rab geranylgeranyltransferase subunit beta

Also known as: GGTB

NCBI Gene: 5876ENSG00000137955UniProt: P53611

The RABGGTB gene encodes the beta-subunit of Rab geranylgeranyl-transferase, which catalyzes the post-translational addition of geranylgeranyl groups to Rab GTPases and other proteins including FBXL2 and YKT6, essential for proper cellular membrane targeting and Golgi function. Mutations in RABGGTB cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in early childhood. This represents a disorder of protein prenylation affecting multiple cellular trafficking pathways.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
21
P/LP submissions
0%
P/LP missense
0.68
LOEUF
GOF
Mechanism· predicted
Clinical Summary— RABGGTB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 33 VUS of 78 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.008
Z-score 2.62
OE 0.36 (0.20–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.48Z-score
OE missense 0.69 (0.60–0.80)
125 obs / 181.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.20–0.68)
0≤0.351.4
Missense OE0.69 (0.60–0.80)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 7 / 19.5Missense obs/exp: 125 / 181.2Syn Z: 0.02
DN
0.5772th %ile
GOF
0.83top 10%
LOF
0.3164th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS33
Likely Benign3
18
Pathogenic
3
Likely Pathogenic
33
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
3
0
3
VUS
0
28
5
0
33
Likely Benign
0
0
2
1
3
Benign
0
0
0
0
0
Total02828157

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

View in ClinVar →

Protein Context — Lollipop Plot

RABGGTB · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients