RAB6B

Chr 3

RAB6B, member RAS oncogene family

NCBI Gene: 51560 ENSG00000154917 UniProt: Q9NRW1 OMIM: 615852

Enables myosin V binding activity. Involved in Golgi organization and protein localization to Golgi membrane. Located in Golgi membrane; ciliary basal body; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.33

Clinical Summary— RAB6B

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

16 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.959

Z-score 3.27

OE 0.07 (0.02–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.49Z-score

OE missense 0.40 (0.32–0.50)

55 obs / 137.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.02–0.33)

0≤0.351.4

Missense OE?0.40 (0.32–0.50)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 1 / 14.4Missense obs/exp: 55 / 137.0Syn Z: -0.21

This gene — mechanism propensity

0.7229th %ile

GOF

0.7030th %ile

LOF

0.49top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.33

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	16	0	16
Likely Benign	0	1	1
Benign	0	1	1
Total	16	2	18

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap RAB6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →