UBA1

Chr XXLR

ubiquitin like modifier activating enzyme 1

Also known as: A1S9, A1S9T, A1ST, AMCX1, CFAP124, GXP1, POC20, SMAX2

NCBI Gene: 7317ENSG00000130985UniProt: P22314

The protein encoded by this gene catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It is part of a gene cluster on chromosome Xp11.23. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinal muscular atrophy, X-linked 2, infantileMIM #301830
XLR
VEXAS syndrome, somaticMIM #301054
2
Active trials
20
Pathogenic / LP
374
ClinVar variants
148
Pubs (1 yr)
3.5
Missense Z· constrained
0.11
LOEUF· LoF intolerant
Clinical Summary— UBA1
⚡
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.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 180 VUS of 374 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — UBA1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 6.01
OE 0.02 (0.01–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.48Z-score
OE missense 0.54 (0.49–0.60)
248 obs / 457.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.11)
0≤0.351.4
Missense OE0.54 (0.49–0.60)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 1 / 44.1Missense obs/exp: 248 / 457.1Syn Z: -1.14
LOF
DN
0.2399th %ile
GOF
0.3590th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.11

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

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
VUS180
Likely Benign146
Benign25
Conflicting3
20
Pathogenic
180
VUS
146
Likely Benign
25
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
0
0
0
VUS
1
153
21
5
180
Likely Benign
0
8
70
68
146
Benign
0
5
14
6
25
Conflicting
—3
Total116612579374

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

View in ClinVar →

UBA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Landmark / reviewRecent case evidence
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
VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.
Loeza-Uribe MP et al.·Reumatol Clin (Engl Ed)
2024Review
Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.
Beck DB et al.·N Engl J Med
2020
An update on VEXAS syndrome.
Al-Hakim A et al.·Expert Rev Clin Immunol
2023Review
VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management.
Koster MJ et al.·Am J Hematol
2024Review
Relapsing polychondritis: Best Practice & Clinical Rheumatology.
Mertz P et al.·Best Pract Res Clin Rheumatol
2023Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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