RUSC1

Chr 1

RUN and SH3 domain containing 1

Also known as: NESCA

NCBI Gene: 23623 ENSG00000160753 UniProt: Q9BVN2 OMIM: 617318

Predicted to enable actin binding activity. Involved in protein polyubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Predicted to enable actin binding activity. Involved in protein polyubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.34

Clinical Summary— RUSC1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

52 VUS of 70 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.941

Z-score 4.33

OE 0.16 (0.08–0.34)

Highly constrained

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

Missense Constraint?

1.45Z-score

OE missense 0.82 (0.76–0.89)

413 obs / 504.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.34)

0≤0.351.4

Missense OE?0.82 (0.76–0.89)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 5 / 31.0Missense obs/exp: 413 / 504.4Syn Z: 0.91

This gene — mechanism propensity

0.3793th %ile

GOF

0.5563th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.34

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

70 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	52	0	52
Likely Benign	0	2	2
Benign	0	0	0
Total	52	2	54

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap RUSC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →