DERL1
derlin 1, the group of Rhomboid family
Basic information
Region (hg38): 8:123013170-123042302
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DERL1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 0 | 0 |
Variants in DERL1
This is a list of pathogenic ClinVar variants found in the DERL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-123015455-C-T | not specified | Uncertain significance (Jan 23, 2023) | ||
| 8-123015460-A-G | not specified | Uncertain significance (Jun 03, 2022) | ||
| 8-123015497-C-T | not specified | Uncertain significance (Jun 11, 2024) | ||
| 8-123015553-A-C | not specified | Uncertain significance (Jun 16, 2023) | ||
| 8-123015580-C-T | not specified | Uncertain significance (Jun 10, 2024) | ||
| 8-123019201-T-C | not specified | Uncertain significance (Mar 28, 2023) | ||
| 8-123019204-G-A | not specified | Uncertain significance (Mar 29, 2024) | ||
| 8-123019238-T-C | not specified | Uncertain significance (Sep 22, 2022) | ||
| 8-123019252-A-G | not specified | Uncertain significance (Jun 28, 2023) | ||
| 8-123021492-T-C | not specified | Uncertain significance (Jan 19, 2022) | ||
| 8-123022709-G-A | not specified | Uncertain significance (Jul 05, 2022) | ||
| 8-123024988-C-T | not specified | Uncertain significance (Sep 28, 2022) | ||
| 8-123025015-T-C | not specified | Uncertain significance (Nov 06, 2023) | ||
| 8-123041989-G-A | not specified | Uncertain significance (Jan 26, 2023) | ||
| 8-123042022-A-T | not specified | Uncertain significance (Nov 09, 2021) | ||
| 8-123042023-T-C | not specified | Uncertain significance (Oct 29, 2021) | ||
| 8-123042073-T-C | not specified | Uncertain significance (May 11, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DERL1 | protein_coding | protein_coding | ENST00000259512 | 8 | 29260 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000211 | 0.980 | 125721 | 0 | 25 | 125746 | 0.0000994 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 104 | 141 | 0.735 | 0.00000702 | 1616 |
| Missense in Polyphen | 29 | 43.315 | 0.66951 | 533 | ||
| Synonymous | 0.110 | 51 | 52.0 | 0.981 | 0.00000270 | 482 |
| Loss of Function | 2.07 | 9 | 18.7 | 0.482 | 0.00000113 | 190 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000366 | 0.000365 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000530 | 0.0000527 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000135 | 0.000131 |
| Other | 0.000490 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the misfolded protein (PubMed:15215856). Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333}.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS);Disorders of transmembrane transporters;Disease;Defective CFTR causes cystic fibrosis;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;Asparagine N-linked glycosylation;ABC-family proteins mediated transport;Protein ubiquitination;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;ABC transporter disorders;E3 ubiquitin ligases ubiquitinate target proteins
(Consensus)
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- loftool
- 0.705
- rvis_EVS
- -0.05
- rvis_percentile_EVS
- 49.76
Haploinsufficiency Scores
- pHI
- 0.223
- hipred
- Y
- hipred_score
- 0.625
- ghis
- 0.660
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Derl1
- Phenotype
- growth/size/body region phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- derl1
- Affected structure
- mandibular arch skeleton
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- protein folding;response to unfolded protein;viral process;protein ubiquitination;ubiquitin-dependent ERAD pathway;endoplasmic reticulum unfolded protein response;retrograde protein transport, ER to cytosol;positive regulation of protein ubiquitination;protein destabilization;positive regulation of protein binding;ERAD pathway;establishment of protein localization;protein homooligomerization;transmembrane transport;ER-associated misfolded protein catabolic process
- Cellular component
- early endosome;late endosome;endoplasmic reticulum;signal recognition particle receptor complex;endoplasmic reticulum membrane;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;VCP-NPL4-UFD1 AAA ATPase complex;Derlin-1-VIMP complex;Derlin-1 retrotranslocation complex;signal recognition particle
- Molecular function
- protease binding;protein binding;ubiquitin protein ligase binding;signaling receptor activity;MHC class I protein binding;ATPase binding;ubiquitin-specific protease binding