SEC61B
protein-codingSEC61 translocon subunit beta
Gene summary
The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the beta-subunit protein. The Sec61 subunits are also observed in the post-ER compartment, suggesting that these proteins can escape the ER and recycle back. There is evidence for multiple polyadenylated sites for this transcript. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0008265
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0000447
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0550003
Submitter: ClinGen
SEC61B was first reported in relation to autosomal dominant polycystic liver disease (ADPLD) in 2017 (Besse et al., 2017, PMID: 28375157). Two unique variants (frameshift, start-loss) reported in two probands in one publication are included in this curation (PMID: 28375157). One patient had numerous small liver cysts and 1 kidney cyst and the other had numerous small liver cysts and no kidney cysts. Additional clinical features were not provided. These heterozygous mutations in SEC61B lead to complete loss of function of the affected allele (PMID: 28375157). This gene-disease relationship is also supported by the related roles of ADPLD proteins and in vitro functional assays (PMID:28973524,28375157). In summary, there remains “Limited” evidence supporting the relationship between SEC61B and ADPLD. While more evidence is required to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the Kidney Cystic and Ciliopathy GCEP on 06/10/2020 (SOP Version 7). It was re-evaluated on 08/23/2023 and the classification did not change (SOP Version 9).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEC61B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006808.3. 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 | 0 | |||||
| missense | 8 | 8 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 10 | 0 | 0 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006799.1 | 4 | MANE Select | |
| Ensembl | ENSP00000223641.4 | 4 | MANE Select | |
| Ensembl | ENSP00000474122.1 | 2 | Standard | |
| Ensembl | ENSP00000474122.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein export - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Vibrio cholerae infection - Homo sapiens (human)
- XBP1(S) activates chaperone genes
Biological Process
- obsolete protein import into nucleus, translocation
- SRP-dependent cotranslational protein targeting to membrane, translocation
- ubiquitin-dependent ERAD pathway
- retrograde protein transport, ER to cytosol
- posttranslational protein targeting to membrane, translocation
Molecular Function
- RNA binding
- ARF guanyl-nucleotide exchange factor activity
- protein binding
- P-P-bond-hydrolysis-driven protein transmembrane transporter activity
- epidermal growth factor binding
Cellular Component
- endoplasmic reticulum
- Sec61 translocon complex
- endoplasmic reticulum membrane
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000223641
- Coding exons
- 4
- Length
- 8552
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125745
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.03 | 35 | 56.9 | 0.615 | 0.00000318 | 592 |
| Missense (PolyPhen) | 8 | 18.233 | 0.43876 | 236 | ||
| Synonymous | -1.15 | 29 | 22.1 | 1.31 | 0.00000133 | 211 |
| Loss of Function | 0.849 | 3 | 5.06 | 0.593 | 2.99e-7 | 54 |
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 | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across endoplasmic reticulum (ER) (By similarity). Required for PKD1/Polycystin-1 biogenesis (By similarity). {ECO:0000250|UniProtKB:P60467, ECO:0000250|UniProtKB:Q9CQS8}.;
- Disease
- DISEASE: Note=Loss-of-function SEC61B variations may cause autosomal dominant polycystic liver disease (PCLD) in patients that lack variations in known causative genes, such as PRKCSH and SEC63. {ECO:0000305|PubMed:28375157}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |