RAB39B

Chr XXLR

RAB39B, member RAS oncogene family

Also known as: BGMR, MRX72, WSMN, WSN, XLID72

This protein is a small GTPase that regulates intracellular vesicle trafficking, autophagosome formation, and synaptic transmission by controlling AMPA receptor composition at post-synapses. Loss-of-function mutations cause X-linked intellectual developmental disorder (including Waisman syndrome) through disrupted vesicular trafficking and synaptic function. The condition follows X-linked recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.522 OMIM phenotypes
Clinical SummaryRAB39B
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Gene-Disease Validity (ClinGen)
early-onset parkinsonism-intellectual disability syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.825
Z-score 2.22
OE 0.00 (0.000.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.94Z-score
OE missense 0.41 (0.320.55)
36 obs / 87.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.52)
00.351.4
Missense OE0.41 (0.320.55)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 0 / 5.8Missense obs/exp: 36 / 87.0Syn Z: 0.69
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRAB39B-related intellectual developmental disorder with or without ParkinsonsLOFXLR
DN
0.5771th %ile
GOF
0.6931th %ile
LOF
0.53top 25%

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RAB39B · 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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