UBA5

Chr 3AR

ubiquitin like modifier activating enzyme 5

Also known as: DEE44, EIEE44, SCAR24, THIFP1, UBE1DC1

The protein functions as an E1-like enzyme that catalyzes the first step in ufmylation by activating UFM1 through ATP-dependent adenylation and thioester bond formation, a post-translational modification pathway essential for ribosome recycling, DNA damage response, and reticulophagy. Biallelic mutations cause autosomal recessive spinocerebellar ataxia type 24 and developmental and epileptic encephalopathy 44. Disease mutations can cause pathogenicity through multiple mechanisms including loss-of-function and dominant-negative effects depending on the specific variant.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.722 OMIM phenotypes
Clinical SummaryUBA5
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Gene-Disease Validity (ClinGen)
genetic developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.000
Z-score 2.58
OE 0.43 (0.260.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.29Z-score
OE missense 0.75 (0.660.85)
158 obs / 210.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.260.72)
00.351.4
Missense OE0.75 (0.660.85)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 10 / 23.5Missense obs/exp: 158 / 210.8Syn Z: 1.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveUBA5-related severe infantile-onset encephalopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7036th %ile
GOF
0.6248th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

UBA5 · 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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