UBAP1

Chr 9AD

ubiquitin associated protein 1

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

NCBI Gene: 51271ENSG00000165006UniProt: Q9NZ09

This gene is a member of the UBA domain family, whose members include proteins having connections to ubiquitin and the ubiquitination pathway. The ubiquitin associated domain is thought to be a non-covalent ubiquitin binding domain consisting of a compact three helix bundle. This particular protein originates from a gene locus in a refined region on chromosome 9 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Taking into account its cytogenetic location, this UBA domain family member is being studies as a putative target for mutation in nasopharyngeal carcinomas. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

Spastic paraplegia 80, autosomal dominantMIM #618418
AD
190
ClinVar variants
88
Pathogenic / LP
0.91
pLI score· haploinsufficient
0
Active trials
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.
📋
ClinVar Variants
88 Pathogenic / Likely Pathogenic· 82 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.87Z-score
OE missense 0.85 (0.77–0.95)
240 obs / 281.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.05–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 2 / 16.6Missense obs/exp: 240 / 281.0Syn Z: 0.11

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic16
VUS82
Likely Benign9
Benign7
Conflicting4
72
Pathogenic
16
Likely Pathogenic
82
VUS
9
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
64
0
72
Likely Pathogenic
3
1
12
0
16
VUS
2
68
12
0
82
Likely Benign
0
4
2
3
9
Benign
0
2
5
0
7
Conflicting
—4
Total1375953190

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

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic paraplegia 80, autosomal dominant

MIM #618418

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Orphan Peripheral Neuropathies.
Finsterer J et al.·J Neuromuscul Dis
2021Review
UBAP1 mutations cause juvenile-onset hereditary spastic paraplegias (SPG80) and impair UBAP1 targeting to endosomes.
Nan H et al.·J Hum Genet
2019
Stop-gain mutations in UBAP1 cause pure autosomal-dominant spastic paraplegia.
Lin X et al.·Brain
2019
Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
Bian X et al.·PLoS One
2021
Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin.
Song S et al.·J Cell Mol Med
2024
Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.
Han JH et al.·Genet Med
2024
Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project.
Bourinaris T et al.·Eur J Hum Genet
2020
Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene.
van Blitterswijk M et al.·Mol Neurodegener
2014
Truncating variants in UBAP1 associated with childhood-onset nonsyndromic hereditary spastic paraplegia.
Gu S et al.·Hum Mutat
2020Case report
A novel UBAP1 truncated variant in a Chinese family with hereditary spastic paraplegia.
Wei Q et al.·Mol Genet Genomic Med
2022Case report
Top 10 resultsSearch 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
2025🔓 Open 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
2025🔓 Open 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
2022🔓 Open 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
2022🔓 Open AccessReview
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools