RABL3

Chr 3AD

RAB, member of RAS oncogene family like 3

Also known as: PNCA5

NCBI Gene: 285282 ENSG00000144840 UniProt: Q5HYI8 OMIM: 618542

RABL3 encodes a small GTPase that regulates KRAS prenylation, modulates cell proliferation, and is essential for ciliogenesis by promoting ciliary vesicle formation at the mother centriole. The gene is not highly constrained against loss-of-function variants, and no Mendelian diseases have been definitively associated with RABL3 mutations in humans. While implicated in pancreatic cancer and required for lymphocyte development in model systems, pathogenic variants causing pediatric neurological disorders have not been established.

OMIM ResearchSummary from RefSeq, UniProt

Enables G protein activity. Involved in positive regulation of cilium assembly; regulation of Ras protein signal transduction; and regulation of protein lipidation. Predicted to be located in Golgi apparatus and centrosome. Predicted to be active in endomembrane system. Implicated in pancreatic cancer. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{?Pancreatic cancer, susceptibility to, 5}MIM #618680

UniProtPancreatic cancer 5

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.001

Z-score 1.65

OE 0.52 (0.29–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.43Z-score

OE missense 0.89 (0.77–1.04)

115 obs / 128.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.29–0.97)

0≤0.351.4

Missense OE?0.89 (0.77–1.04)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 7 / 13.5Missense obs/exp: 115 / 128.8Syn Z: -0.13

Background carrier burden — how many people carry a rare variant somewhere in RABL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

281 rare PASS variants

Rare truncating (LoF)

1 in 3,000

58 rare PASS variants

Rare synonymous (reference)

1 in 620

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RABL3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 360	1 in 2,800
South Asian	~43k	1 in 220	1 in 8,600
Remaining (unassigned)	~30k	1 in 220	1 in 4,300
European (Finnish)	~27k	1 in 650	≈ 1 in 27,000
Admixed American	~22k	1 in 240	≈ 1 in 7,400
African / African American	~21k	1 in 230	≈ 1 in 10,000
East Asian	~20k	1 in 500	1 in 4,000
Ashkenazi Jewish	~13k	1 in 930	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 410	≈ 1 in 950

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 8.? see exons ↓