RUSC2

Chr 9AR

RUN and SH3 domain containing 2

ENSG00000198853UniProt: Q8N2Y8OMIM: 611053

The protein associates with the adapter-like complex 4 (AP-4) and interacts with Rab1b and GM130, functioning in vesicular trafficking at the trans-Golgi network. Mutations cause autosomal recessive intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.253).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.251 OMIM phenotype
Clinical Summary— RUSC2
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Gene-Disease Validity (ClinGen)
intellectual disability, autosomal recessive 61 · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 38 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.999
Z-score 6.02
OE 0.14 (0.08–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.95Z-score
OE missense 0.91 (0.86–0.96)
794 obs / 873.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.08–0.25)
0≤0.351.4
Missense OE0.91 (0.86–0.96)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 8 / 57.1Missense obs/exp: 794 / 873.0Syn Z: 0.04
DN
0.3395th %ile
GOF
0.4579th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 33% of P/LP variants are LoF · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS38
Likely Benign56
5
Pathogenic
1
Likely Pathogenic
38
VUS
56
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
3
0
5
Likely Pathogenic
0
0
1
0
1
VUS
1
35
2
0
38
Likely Benign
0
0
7
49
56
Benign
0
0
0
0
0
Total3351349100

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

View in ClinVar →

Protein Context — Lollipop Plot

RUSC2 · 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 5 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