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RUFY3

Chr 4

RUN and FYVE domain containing 3

Also known as: RIPX, SINGAR1, ZFYVE30

RUFY3 encodes a protein that promotes retrograde transport of endolysosomes along microtubules and is required for maintenance of neuronal polarity and axon formation. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and neurological features. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.46
Clinical SummaryRUFY3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.021
Z-score 4.22
OE 0.28 (0.170.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.48Z-score
OE missense 0.61 (0.550.69)
202 obs / 328.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.170.46)
00.351.4
Missense OE0.61 (0.550.69)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 11 / 39.7Missense obs/exp: 202 / 328.7Syn Z: 0.68
DN
0.78top 25%
GOF
0.72top 25%
LOF
0.3162th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RUFY3 · 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.

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Clinical Literature
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