SAR1B
protein-codingsecretion associated Ras related GTPase 1B, the group of ARF GTPase family|COPII coat complex
Gene summary
The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]
- SARA2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009528
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009528
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009528
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Musculoskeletal; Neurologic
Intervention: Gastrointestinal
Rationale: Individuals typically present in infancy with with steatorrhea and failure to thrive, and dietary measures (maintenance of adequate caloric intake on a low-long chain fat diet consisting of polyunsaturated fatty acids, with supplementation of lipid soluble vitamins, including large amounts of vitamin E, and essential fatty acids) can be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SAR1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016103.4. 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 | 2 | 39 | 41 | |||
| missense | 2 | 3 | 51 | 56 | ||
| nonsense | 6 | 1 | 7 | |||
| start loss | 0 | |||||
| frameshift | 9 | 1 | 10 | |||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | 6 | ||
| Total | 18 | 7 | 56 | 39 | 0 | 120 |
Highest pathogenic variant AF is 0.000040297833
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057187.1 | 6 | MANE Select | |
| Ensembl | ENSP00000385432.2 | 6 | MANE Select | |
| RefSeq | NP_001028675.1 | 6 | Standard | |
| Ensembl | ENSP00000404997.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sar1b | Danio rerio | Structure: rhombic lip Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Legionellosis - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
- Chylomicron assembly
- Vesicle-mediated transport
Biological Process
- antigen processing and presentation of peptide antigen via MHC class I
- regulation of COPII vesicle coating
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- vesicle organization
Molecular Function
- GTPase activity
- GTP binding
- metal ion binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- ER to Golgi transport vesicle membrane
- COPII vesicle coat
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000402673
- Coding exons
- 6
- Length
- 48128
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125746
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.814 | 83 | 107 | 0.778 | 0.00000528 | 1283 |
| Missense (PolyPhen) | 16 | 34.442 | 0.46455 | 449 | ||
| Synonymous | 0.324 | 36 | 38.6 | 0.934 | 0.00000211 | 367 |
| Loss of Function | 1.60 | 6 | 12.0 | 0.501 | 7.40e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in transport from the endoplasmic reticulum to the Golgi apparatus. Activated by the guanine nucleotide exchange factor PREB. Involved in the selection of the protein cargo and the assembly of the COPII coat complex.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.458
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.398
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |