SEL1L
protein-codingSEL1L adaptor subunit of ERAD E3 ubiquitin ligase
Gene summary
The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: Allergy/Immunology/Infectious
Rationale: The condition has been described as involving early-onset agammaglobulinemia and recurrent, severe infections, and awareness may allow preventative measures and early and aggressive treatment of infections
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEL1L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005065.6. 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 | 2 | 1 | 1 | 4 | ||
| missense | 1 | 85 | 1 | 1 | 88 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 0 | 91 | 2 | 2 | 96 |
Highest pathogenic variant AF is 6.841583e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005056.3 | 21 | MANE Select | |
| Ensembl | ENSP00000337053.4 | 21 | MANE Select | |
| RefSeq | NP_001231913.1 | 8 | Standard | |
| Ensembl | ENSP00000450709.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sel1l | Danio rerio | Structure: post-vent vasculature Quality: hemorrhagic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Disorders of transmembrane transporters
- Disease
- Signal Transduction
- Defective CFTR causes cystic fibrosis
Biological Process
- triglyceride metabolic process
- Notch signaling pathway
- protein secretion
- ubiquitin-dependent ERAD pathway
- retrograde protein transport, ER to cytosol
Molecular Function
- protein binding
Cellular Component
- Hrd1p ubiquitin ligase complex
- Hrd1p ubiquitin ligase ERAD-L complex
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336735
- Coding exons
- 21
- Length
- 62313
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125747
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 289 | 430 | 0.672 | 0.0000218 | 5191 |
| Missense (PolyPhen) | 84 | 167.27 | 0.50218 | 1968 | ||
| Synonymous | 0.156 | 153 | 155 | 0.984 | 0.00000794 | 1484 |
| Loss of Function | 5.32 | 8 | 47.6 | 0.168 | 0.00000228 | 584 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| 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) | 0.000089 | 0.000088 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:16186509). Enhances SYVN1 stability. Plays a role in LPL maturation and secretion. Required for normal differentiation of the pancreas epithelium, and for normal exocrine function and survival of pancreatic cells. May play a role in Notch signaling. {ECO:0000250|UniProtKB:Q9Z2G6, ECO:0000269|PubMed:16186509}.;
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- LoFtool
- 0.492
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.952
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |