RAB26

Chr 16

RAB26, member RAS oncogene family

Also known as: V46133

NCBI Gene: 25837 ENSG00000167964 UniProt: Q9ULW5 OMIM: 605455

RAB26 encodes a small GTPase that regulates intracellular vesicle trafficking and transport of specific proteins from the Golgi to the cell membrane, and plays a role in secretory granule maturation and secretion in stomach and salivary gland cells. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 1.589), and no clear Mendelian diseases have been established from RAB26 mutations. Based on current evidence, RAB26 variants are unlikely to cause monogenic pediatric neurological disorders.

OMIM ResearchSummary from RefSeq, UniProt

Members of the RAB protein family, including RAB26, are important regulators of vesicular fusion and trafficking. The RAB family of small G proteins regulates intercellular vesicle trafficking, including exocytosis, endocytosis, and recycling (summary by Seki et al., 2000 [PubMed 11043516]).[supplied by OMIM, Nov 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.59

Clinical Summary— RAB26

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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· 66 VUS of 73 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?

1.59LOEUF

pLI 0.000

Z-score 0.03

OE 0.99 (0.63–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.81Z-score

OE missense 1.20 (1.05–1.37)

156 obs / 130.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.63–1.59)

0≤0.351.4

Missense OE?1.20 (1.05–1.37)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 12 / 12.1Missense obs/exp: 156 / 130.0Syn Z: -1.81

This gene — mechanism propensity

0.82top 10%

GOF

0.77top 25%

LOF

0.3258th %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

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS66

Likely Benign2

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	66	0	66
Likely Benign	2	0	2
Benign	0	0	0
Total	68	1	69

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap RAB26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →