RAB40AL

Chr X

RAB40A like

Also known as: MRXSMP, RAR2, RLGP

NCBI Gene: 282808ENSG00000102128UniProt: P0C0E4

The protein functions as a Rab small GTPase that regulates intracellular membrane trafficking and may serve as a substrate-recognition component of an E3 ubiquitin ligase complex that targets proteins for degradation. Mutations in this gene are associated with Duchenne muscular dystrophy, which primarily affects skeletal and cardiac muscle with onset typically in early childhood. The gene shows relatively low constraint to loss-of-function variation (pLI 0.31, LOEUF 1.87).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
73
P/LP submissions
0%
P/LP missense
1.86
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— RAB40AL
🧬
Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLRefuted

Refuted — evidence has disproved this relationship

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 43 VUS of 122 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
1.86LOEUF
pLI 0.313
Z-score 0.51
OE 0.00 (0.00–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.23Z-score
OE missense 1.06 (0.92–1.22)
136 obs / 128.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.86)
0≤0.351.4
Missense OE1.06 (0.92–1.22)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 0 / 0.3Missense obs/exp: 136 / 128.6Syn Z: 0.47
DN
0.83top 10%
GOF
0.79top 25%
LOF
0.3454th %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

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
VUS43
Likely Benign3
Benign8
68
Pathogenic
43
VUS
3
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
68
0
68
Likely Pathogenic
0
0
0
0
0
VUS
0
38
5
0
43
Likely Benign
0
1
0
2
3
Benign
0
2
0
6
8
Total041738122

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB40AL · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients