SBDS
protein-codingSBDS ribosome maturation factor, the group of Ribosomal biogenesis factors
Gene summary
This gene encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The encoded protein interacts with elongation factor-like GTPase 1 to disassociate eukaryotic initiation factor 6 from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S subunit. Mutations within this gene are associated with the autosomal recessive disorder Shwachman-Bodian-Diamond syndrome. This gene has a closely linked pseudogene that is distally located. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009833
Submitter: ClinGen
Variants in SBDS gene have been reported in more than 350 individuals with autosomal recessive (AR) Shwachman-Diamond Syndrome since the first publication in 2003 (Boocock GR et al; PMID: 12496757). Biallelic inheritance of more than 20 unique variants that are predicted to result in a hypomorphic protein have been reported in >90% of the individuals with clinical diagnosis of Shwachman-Diamond Syndrome. SBDS is reported to play an essential role in ribosome biogenesis. Two of the recurring variants, as well as some others, arise from a gene-conversion event between SBDS and its pseudogene SBDSP1, and they are found in 60% and 90% of the affected individuals with pathogenic SBDS variants either together or with another variant, respectively. This gene-disease relationship is supported by animal models, rescue experiments, and functional experiments. In summary, SBDS is definitively associated with autosomal recessive Shwachman-Diamond Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
Inheritance Pattern: AR
Disease ID:MONDO:0044204
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009833
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0044204
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0044204
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic
Intervention: Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Oncologic
Rationale: In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure, as well as associated myelodysplasia, which has been reported, may reduce morbidity; BMT and HSCT have been reported; In Shwachman-Diamond syndrome, medical treatment (eg, pancreatic enzymes, fat-soluble vitamins) can be effective to treat pancreatic exocrine insufficiency; Blood/platelet transfusions may be necessary; Due to neutropenia and infectious risk, G-CSF and other prophylactic measures (eg antibiotics), as well as early and aggressive treatment of infections, may be beneficial, but prolonged use of agents such as G-CSF may have adverse effects; Regular surveillance for hematologic anomalies is recommended; Awareness of the risk of malignant transformation may allow early detection and management; HSCT use has been reported
Comments: Heterozygous variants can result in incompletely penetrant aplastic anemia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SBDS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016038.4. 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 | 118 | 1 | 120 | ||
| missense | 3 | 13 | 254 | 1 | 271 | |
| nonsense | 2 | 6 | 8 | |||
| start loss | 1 | 1 | ||||
| frameshift | 10 | 11 | 21 | |||
| splice donor/acceptor (+/-2bp) | 5 | 10 | 15 | |||
| Total | 20 | 41 | 255 | 119 | 1 | 436 |
Highest pathogenic variant AF is 0.0036324752
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057122.2 | 5 | MANE Select | |
| Ensembl | ENSP00000246868.2 | 5 | MANE Select | |
| Ensembl | ENSP00000394586.1 | 3 | Standard | |
| Ensembl | ENSP00000513460.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sbds | Danio rerio | Structure: granulocyte Quality: position abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
Biological Process
- inner cell mass cell proliferation
- rRNA processing
- mitotic spindle organization
- cell population proliferation
- bone mineralization
Molecular Function
- RNA binding
- protein binding
- microtubule binding
- rRNA binding
- ribosome binding
Cellular Component
- spindle pole
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246868
- Coding exons
- 5
- Length
- 7925
- Individuals with no LoFs
- 124708
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 1037
- Defined
- 125747
- p
- 0.00414
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.593 | 112 | 131 | 0.854 | 0.00000671 | 1651 |
| Missense (PolyPhen) | 37 | 46.763 | 0.79122 | 573 | ||
| Synonymous | -1.20 | 58 | 47.5 | 1.22 | 0.00000253 | 450 |
| Loss of Function | 1.02 | 8 | 11.8 | 0.680 | 6.83e-7 | 143 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.0012 | notable |
| Latino/Admixed American | 0.0032 | 0.0032 | notable |
| Ashkenazi Jewish | 0.0024 | 0.0024 | notable |
| East Asian | 0.0052 | 0.0052 | notable |
| Finnish | 0.0096 | 0.0096 | notable |
| European (Non-Finnish) | 0.0039 | 0.0039 | notable |
| South Asian | 0.0037 | 0.0037 | notable |
| Other | 0.0047 | 0.0047 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP- dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation. {ECO:0000269|PubMed:17643419, ECO:0000269|PubMed:19602484, ECO:0000269|PubMed:19759903, ECO:0000269|PubMed:21536732}.;
Recessive Scores
- pRec
- 0.388
Intolerance Scores
- LoFtool
- 0.375
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.98
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.939
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |