UFL1

Chr 6

UFM1 specific ligase 1

Also known as: KIAA0776, Maxer, NLBP, RCAD

NCBI Gene: 23376ENSG00000014123UniProt: O94874

Enables UFM1 ligase activity and protein kinase binding activity. Involved in several processes, including positive regulation of reticulophagy; regulation of intracellular signal transduction; and regulation of primary metabolic process. Acts upstream of or within several processes, including positive regulation of cell population proliferation; regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to endoplasmic reticulum stress. Located in cytoplasm; nucleus; and site of double-strand break. Part of protein-containing complex. Is active in endoplasmic reticulum membrane and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jul 2025]

144
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UFL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 125 VUS of 144 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.84LOEUF
pLI 0.000
Z-score 2.38
OE 0.61 (0.44–0.84)
Tolerant

Typical tolerance to LoF variation

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.
0.19Z-score
OE missense 0.97 (0.90–1.06)
393 obs / 403.7 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.0.61 (0.44–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.90–1.06)
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.1.00
0≤1.21.6
LoF obs/exp: 26 / 42.8Missense obs/exp: 393 / 403.7Syn Z: -0.04

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS125
Likely Benign1
Benign3
14
Pathogenic
1
Likely Pathogenic
125
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
117
8
0
125
Likely Benign
0
1
0
0
1
Benign
0
2
0
1
3
Total0120231144

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

View in ClinVar →

Protein Context — Lollipop Plot

UFL1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.
Wang Z et al.·Autophagy
2024
Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.
Zhou J et al.·Proc Natl Acad Sci U S A
2023
DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis.
Jin H et al.·Cell Death Dis
2024
FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.
Wong D et al.·Circ Res
2023Meta-analysis
Unveiling migraine subtype heterogeneity and risk loci: integrated genome-wide association study and single-cell transcriptomics discovery.
Wei S et al.·J Headache Pain
2025
PARP1 UFMylation ensures the stability of stalled replication forks.
Gong Y et al.·Proc Natl Acad Sci U S A
2024
The UFL1-AKT positive feedback loop promotes breast cancer progression by enhancing lipid synthesis.
Meng F et al.·Nat Commun
2026
A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance.
Sun N et al.·Neuro Oncol
2025
Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.
Tang X et al.·Reprod Biol Endocrinol
2022
UFMylation in lipid metabolism disorders-associated diseases.
Ning ZP et al.·Mol Biol Rep
2026Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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