UBAP1

Chr 9AD

ubiquitin associated protein 1

Also known as: NAG20, SPG80, UAP, UBAP, UBAP-1

NCBI Gene: 51271ENSG00000165006UniProt: Q9NZ09OMIM: 609787

The protein is a component of the ESCRT-I complex that binds ubiquitinated cargo proteins and regulates their sorting into multivesicular bodies and proteasomal degradation. Mutations cause spastic paraplegia 80 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.91, LOEUF = 0.38), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.381 OMIM phenotype
Clinical Summary— UBAP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
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
0.38LOEUF
pLI 0.912
Z-score 3.32
OE 0.12 (0.05–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.87Z-score
OE missense 0.85 (0.77–0.95)
240 obs / 281.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.05–0.38)
0≤0.351.4
Missense OE0.85 (0.77–0.95)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 2 / 16.6Missense obs/exp: 240 / 281.0Syn Z: 0.11
DN
0.4488th %ile
GOF
0.4875th %ile
LOF
0.62top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.38
DN1 literature citation

Literature Evidence

DNOur biochemical and cell biology evidence collectively points to a dominant-negative pathomechanism in which the truncated gene products from the disease alleles dysregulate endosomal processing and ubiquitinated protein sorting, thereby promoting neurodegeneration, potentially as mediated by apoptoPMID:31203368
LOFWe identified three novel heterozygous loss of function mutations (c.425_426delAG, c.312delC, and c.535G>T) in the UBAP1 gene as the genetic cause of a new type of HSP (SPG80).PMID:31515522

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

ClinVar

Protein Context — Lollipop Plot

UBAP1 · 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
4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80.
Shimozono K et al.·Int J Mol Sci
2025Open AccessFunctional
Ubiquitin-Associated Protein 1 (UBAP1) Gene Mutation in a 36-Year-Old Filipino Male With Spastic Paraplegia: A Case Report.
Solijon KKL et al.·Cureus
2025Open AccessCase report
ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells.
Lu D et al.·Cell Rep
2024
Ubap1 knock-in mice reproduced the phenotype of SPG80.
Shimozono K et al.·J Hum Genet
2022Open Access
A novel mutation in the UBAP1 gene causing hereditary spastic paraplegia: A case report and overview of the genotype-phenotype correlation.
Li P et al.·Front Genet
2022Open AccessReview
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