RHOBTB2

Chr 8AD

Rho related BTB domain containing 2

Also known as: DBC2, DEE64, EIEE64, p83

The protein is a small Rho GTPase that interacts with cullin-3, a ubiquitin E3 ligase necessary for mitotic cell division. Gain-of-function mutations cause developmental and epileptic encephalopathy 64 through autosomal dominant inheritance. The protein normally functions as a candidate tumor suppressor that inhibits growth and spread of certain cancers.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
MultiplemechanismADLOEUF 0.501 OMIM phenotype
Clinical SummaryRHOBTB2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.013
Z-score 3.83
OE 0.29 (0.180.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.66Z-score
OE missense 0.66 (0.600.72)
322 obs / 487.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.29 (0.180.50)
00.351.4
Missense OE0.66 (0.600.72)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 10 / 34.1Missense obs/exp: 322 / 487.2Syn Z: 0.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRHOBTB2-related developmental and epileptic encephalopathyOTHERAD
DN
0.7132th %ile
GOF
0.7028th %ile
LOF
0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RHOBTB2 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC