UBQLN1

Chr 9

ubiquilin 1

Also known as: DA41, DSK2, PLIC-1, UBQN, XDRP1

The protein mediates proteasomal targeting of misfolded proteins for degradation by binding to polyubiquitin chains and interacting with proteasome subunits, and regulates macroautophagy, endoplasmic reticulum-associated protein degradation, and autophagosome formation. Loss-of-function mutations in UBQLN1 cause autosomal dominant spastic paraplegia and frontotemporal dementia through impaired protein degradation pathways. The gene is highly intolerant to loss-of-function variation, supporting haploinsufficiency as the disease mechanism.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.22
Clinical SummaryUBQLN1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.999
Z-score 4.60
OE 0.07 (0.030.22)
Highly constrained

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

Missense Constraint
2.39Z-score
OE missense 0.62 (0.550.70)
194 obs / 312.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.22)
00.351.4
Missense OE0.62 (0.550.70)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 2 / 28.4Missense obs/exp: 194 / 312.9Syn Z: -0.44
DN
0.4289th %ile
GOF
0.3491th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.22

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

UBQLN1 · 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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