RABL2B

Chr 22

RAB, member of RAS oncogene family like 2B

NCBI Gene: 11158 ENSG00000079974 UniProt: Q9UNT1 OMIM: 605413

The RABL2B protein is a small GTPase that regulates ciliary assembly by controlling the entry of intraflagellar transport complexes into cilia. Mutations cause autosomal recessive primary ciliary dyskinesia with typical respiratory symptoms and potential multi-organ involvement including kidney and brain abnormalities. The gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The RABL2B protein is a member of the RAB gene family which belongs to the RAS GTPase superfamily. RABL2B is located within a subtelomeric region of 22q13.3. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.50

Clinical Summary— RABL2B

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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

1 unique Pathogenic / Likely Pathogenic· 39 VUS of 51 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?

1.50LOEUF

pLI 0.000

Z-score 0.34

OE 0.89 (0.55–1.50)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.01 (0.87–1.16)

129 obs / 128.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.89 (0.55–1.50)

0≤0.351.4

Missense OE?1.01 (0.87–1.16)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 11.2Missense obs/exp: 129 / 128.3Syn Z: -0.02

This gene — mechanism propensity

0.81top 10%

GOF

0.84top 5%

LOF

0.2190th %ile

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

GOFprediction above median

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

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS39

Likely Benign1

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	1	1
Likely Pathogenic	0	0	0	0
VUS	1	38	0	39
Likely Benign	1	0	0	1
Benign	0	0	1	1
Total	2	38	2	42

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap RABL2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →