HERPUD1
protein-codinghomocysteine inducible ER protein with ubiquitin like domain 1
Gene summary
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.7 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 HERPUD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014685.4. 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 | 3 | ||||
| missense | 52 | 3 | 55 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 0 | 59 | 3 | 0 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055500.1 | 8 | MANE Select | |
| Ensembl | ENSP00000409555.2 | 8 | MANE Select | |
| RefSeq | NP_001010989.1 | 8 | Standard | |
| RefSeq | NP_001259032.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- ATF4 activates genes
- VEGFA-VEGFR2 Signaling Pathway
- Exercise-induced Circadian Regulation
Biological Process
- ubiquitin-dependent protein catabolic process
- response to unfolded protein
- retrograde protein transport, ER to cytosol
- regulation of protein ubiquitination
- positive regulation of protein binding
Molecular Function
- molecular_function
- protein binding
- ion channel binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- membrane
- calcium channel complex
- Lewy body core
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000439977
- Coding exons
- 8
- Length
- 11839
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.800 | 187 | 220 | 0.848 | 0.0000112 | 2556 |
| Missense (PolyPhen) | 38 | 67.144 | 0.56595 | 854 | ||
| Synonymous | 0.417 | 77 | 81.8 | 0.941 | 0.00000435 | 767 |
| Loss of Function | 4.00 | 1 | 20.6 | 0.0486 | 0.00000105 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Could enhance presenilin-mediated amyloid-beta protein 40 generation. Binds to ubiquilins and this interaction is required for efficient degradation of CD3D via the ERAD pathway (PubMed:18307982). {ECO:0000269|PubMed:16289116, ECO:0000269|PubMed:18307982}.;
Recessive Scores
- pRec
- 0.285
Intolerance Scores
- LoFtool
- 0.761
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.928
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |