UFD1
protein-codingubiquitin recognition factor in ER associated degradation 1
Gene summary
The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]
- UFD1L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UFD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005659.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 28 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 29 | 3 | 1 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005650.2 | 12 | MANE Select | |
| Ensembl | ENSP00000263202.9 | 12 | MANE Select | |
| RefSeq | NP_001030324.2 | 12 | Standard | |
| RefSeq | NP_001349839.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ufd1l | Danio rerio | Structure: anatomical system Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- DNA Repair
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
Biological Process
- skeletal system development
- ubiquitin-dependent protein catabolic process
- protein deubiquitination
- retrograde protein transport, ER to cytosol
- negative regulation of type I interferon production
Molecular Function
- thiol-dependent ubiquitin-specific protease activity
- signaling receptor binding
- protein binding
- K48-linked polyubiquitin modification-dependent protein binding
- protein-containing complex binding
Cellular Component
- nucleus
- nucleoplasm
- endoplasmic reticulum
- cytosol
- VCP-NPL4-UFD1 AAA ATPase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263202
- Coding exons
- 12
- Length
- 29306
- Individuals with no LoFs
- 125745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125747
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.71 | 80 | 183 | 0.437 | 0.0000103 | 2027 |
| Missense (PolyPhen) | 11 | 60.372 | 0.1822 | 744 | ||
| Synonymous | 1.02 | 58 | 68.8 | 0.843 | 0.00000420 | 566 |
| Loss of Function | 4.04 | 1 | 21.0 | 0.0477 | 0.00000117 | 233 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-derived structures (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and NPLOC4, which binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES53, ECO:0000269|PubMed:26471729}.;
Recessive Scores
- pRec
- 0.160
Intolerance Scores
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.26
Essentials
- Essential (gene trap)
- E