SEC61A2
protein-codingSEC61 translocon subunit alpha 2
Gene summary
The protein encoded by this gene has similarity to a mouse protein which suggests a role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. It may also be required for the assembly of membrane and secretory proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.3 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 SEC61A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018144.4. 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 | 1 | 1 | ||||
| missense | 35 | 1 | 36 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 1 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060614.2 | 12 | MANE Select | |
| Ensembl | ENSP00000298428.9 | 12 | MANE Select | |
| RefSeq | NP_001136099.1 | 12 | Standard | |
| RefSeq | NP_001136100.1 | 11 | 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
- SRP-dependent cotranslational protein targeting to membrane, translocation
- posttranslational protein targeting to endoplasmic reticulum membrane
- biological_process
Molecular Function
- molecular_function
- signal sequence binding
- protein transmembrane transporter activity
- ribosome binding
Cellular Component
- endoplasmic reticulum
- Sec61 translocon complex
- endoplasmic reticulum membrane
- cytosol
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000298428
- Coding exons
- 12
- Length
- 40325
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.00 | 131 | 270 | 0.486 | 0.0000141 | 3079 |
| Missense (PolyPhen) | 21 | 80.559 | 0.26068 | 906 | ||
| Synonymous | 1.38 | 85 | 103 | 0.827 | 0.00000585 | 967 |
| Loss of Function | 3.34 | 9 | 28.1 | 0.320 | 0.00000171 | 304 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Appears to play a crucial role in the insertion of secretory and membrane polypeptides into the ER. It is required for assembly of membrane and secretory proteins. Found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.192
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.544
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |