RUSF1

Chr 16

RUS family member 1

Also known as: C16orf58, RUS

NCBI Gene: 64755ENSG00000140688UniProt: Q96GQ5

RUSF1 encodes a transmembrane protein with a conserved DUF647 domain that may mediate protein-protein interactions. Mutations cause autosomal recessive intellectual disability with microcephaly, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, consistent with its role in neurodevelopmental disorders.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 1.39
Clinical Summary— RUSF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 53 VUS of 112 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
1.39LOEUF
pLI 0.000
Z-score -0.01
OE 1.00 (0.73–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.18Z-score
OE missense 1.03 (0.93–1.14)
269 obs / 261.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.00 (0.73–1.39)
0≤0.351.4
Missense OE1.03 (0.93–1.14)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 26 / 26.0Missense obs/exp: 269 / 261.0Syn Z: 0.57
DN
0.6939th %ile
GOF
0.5367th %ile
LOF
0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-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
LOF27% of P/LP variants are LoF

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic4
VUS53
Likely Benign6
Benign2
Conflicting6
7
Pathogenic
4
Likely Pathogenic
53
VUS
6
Likely Benign
2
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
3
0
1
0
4
VUS
1
36
9
7
53
Likely Benign
0
2
3
1
6
Benign
0
1
1
0
2
Conflicting
—6
Total43921878

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

View in ClinVar →

Protein Context — Lollipop Plot

RUSF1 · 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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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