RUBCNL

Chr 13

rubicon like autophagy enhancer

Also known as: C13orf18, KIAA0226L, PACER

The protein regulates autophagy by promoting autophagosome maturation and facilitating the fusion of autophagosomes with lysosomes, and also regulates lipid and glycogen homeostasis. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy, cataracts, and digestive abnormalities. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.27
Clinical SummaryRUBCNL
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 6 VUS of 80 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.27LOEUF
pLI 0.000
Z-score 0.37
OE 0.93 (0.691.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.27Z-score
OE missense 0.96 (0.881.05)
332 obs / 345.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.93 (0.691.27)
00.351.4
Missense OE0.96 (0.881.05)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 28 / 30.2Missense obs/exp: 332 / 345.9Syn Z: 0.32
DN
0.6745th %ile
GOF
0.6248th %ile
LOF
0.3744th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

80 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic1
VUS6
Benign1
54
Pathogenic
1
Likely Pathogenic
6
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
54
Likely Pathogenic
1
VUS
6
Likely Benign
0
Benign
1
Total62

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RUBCNL · 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.

Search ClinicalTrials.gov →
Clinical Literature
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