UFD1

Chr 22AD

ubiquitin recognition factor in ER associated degradation 1

Also known as: UFD1L

UFD1 encodes an essential component of the ubiquitin-dependent proteolytic pathway that forms a complex with VCP and NPLOC4 to degrade misfolded proteins and regulate nuclear envelope formation during mitosis. Mutations cause autosomal dominant Charcot-Marie-Tooth disease type 2Y, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, and inclusion body myopathy with early-onset Paget disease and frontotemporal dementia. The gene is highly constrained against loss-of-function variants, reflecting its essential cellular functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.233 OMIM phenotypes
Clinical SummaryUFD1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.996
Z-score 4.04
OE 0.05 (0.020.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.71Z-score
OE missense 0.44 (0.360.53)
80 obs / 183.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.23)
00.351.4
Missense OE0.44 (0.360.53)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 1 / 21.0Missense obs/exp: 80 / 183.2Syn Z: 1.02
DN
0.4487th %ile
GOF
0.2895th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.23

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

Protein Context — Lollipop Plot

UFD1 · 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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