SBDS

SBDS ribosome maturation factor, the group of Ribosomal biogenesis factors

Basic information

Region (hg38): 7:66987679-66995693

Links

ENSG00000126524 ∙ NCBI:51119 ∙ OMIM:607444 ∙ HGNC:19440 ∙ Uniprot:Q9Y3A5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Shwachman-Diamond syndrome 1 (Definitive), mode of inheritance: AR
• Shwachman-Diamond syndrome 1 (Strong), mode of inheritance: AR
• Shwachman-Diamond syndrome (Supportive), mode of inheritance: AR
• Shwachman-Diamond syndrome 1 (Strong), mode of inheritance: AR
• Shwachman-Diamond syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Shwachman-Diamond syndrome 1; Aplastic anemia	AD/AR	Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Oncologic	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	Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic	14221166; 7264801; 8942739; 8759887; 9359520; 10467990; 10393609; 12183725; 12496757; 14984468; 15769891; 17376717; 17400792; 17478638; 17916435; 20301722; 22554078; 22992231; 23305959; 23351992
Heterozygous variants can result in incompletely penetrant aplastic anemia

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SBDS gene.

• not provided (45 variants)
• Shwachman-Diamond syndrome 1 (35 variants)
• Inborn genetic diseases (34 variants)
• Aplastic anemia (25 variants)
• not specified (16 variants)
• Aplastic anemia;Shwachman-Diamond syndrome 1 (4 variants)
• Shwachman-Diamond syndrome 1;Aplastic anemia (3 variants)
• Agenesis of permanent teeth;Deeply set eye;Splenomegaly;Short stature;Microcephaly (1 variants)
• SBDS-related condition (1 variants)
• Splenomegaly;Microcephaly;Agenesis of permanent teeth;Deeply set eye;Short stature (1 variants)
• Intellectual disability (1 variants)
• Shwachman syndrome (1 variants)
• Aplastic anemia, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SBDS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	3	14
missense		8	25	1		34
nonsense	2	4				6
start loss						0
frameshift	9	5				14
inframe indel		1				1
splice donor/acceptor (+/-2bp)	3	7				10
splice region			3			3
non coding				1	16	17
Total	14	25	25	13	19

Highest pathogenic variant AF is 0.0000197

Variants in SBDS

This is a list of pathogenic ClinVar variants found in the SBDS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-66988302-C-T			Benign (Mar 03, 2015)
7-66988388-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
7-66988390-CCTT-C			Likely pathogenic (Dec 08, 2017)
7-66988405-T-C			Uncertain significance (Oct 01, 2017)
7-66988413-G-A		Inborn genetic diseases	Likely benign (Dec 23, 2022)
7-66988429-C-A		Inborn genetic diseases	Uncertain significance (Mar 31, 2023)
7-66988453-A-G		not specified	Uncertain significance (May 22, 2017)
7-66988458-C-T		Inborn genetic diseases	Likely benign (Jul 26, 2019)
7-66988460-C-G			Uncertain significance (Feb 24, 2023)
7-66988471-C-T		Shwachman-Diamond syndrome 1 • Aplastic anemia	Likely pathogenic (Aug 01, 2023)
7-66988472-G-A		Shwachman-Diamond syndrome 1 • Aplastic anemia	Pathogenic/Likely pathogenic (Jul 07, 2023)
7-66988473-G-A		Shwachman-Diamond syndrome 1 • not specified • Inborn genetic diseases	Benign (Jul 07, 2023)
7-66988489-A-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
7-66988489-A-G		Shwachman-Diamond syndrome 1 • not specified • Inborn genetic diseases	Benign/Likely benign (Jul 07, 2023)
7-66988495-C-T		Shwachman-Diamond syndrome 1	Likely pathogenic (Dec 28, 2021)
7-66988498-AC-A		Shwachman-Diamond syndrome 1	Pathogenic (Sep 20, 2018)
7-66991134-T-TA			Likely pathogenic (Jun 02, 2017)
7-66991136-C-G		Shwachman-Diamond syndrome 1	Pathogenic (Jul 18, 2019)
7-66991136-C-T		Aplastic anemia	Likely pathogenic (Feb 19, 2023)
7-66991148-G-A		Inborn genetic diseases	Pathogenic (Apr 14, 2015)
7-66991182-C-T		Inborn genetic diseases	Likely benign (May 18, 2020)
7-66991220-T-C		Shwachman-Diamond syndrome 1	Uncertain significance (Feb 12, 2021)
7-66991237-C-T		Inborn genetic diseases	Uncertain significance (Sep 07, 2021)
7-66991237-CG-C		Aplastic anemia	Likely pathogenic (Oct 07, 2023)
7-66991238-G-A		Aplastic anemia;Shwachman-Diamond syndrome 1 • Aplastic anemia	Conflicting classifications of pathogenicity (Jan 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SBDS	protein_coding	protein_coding	ENST00000246868	5	7925

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000621	0.728	124708	2	1037	125747	0.00414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.593	112	131	0.854	0.00000671	1651
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00438	0.00438
Ashkenazi Jewish	0.00238	0.00238
East Asian	0.00518	0.00518
Finnish	0.00962	0.00956
European (Non-Finnish)	0.00389	0.00389
Middle Eastern	0.00518	0.00518
South Asian	0.00373	0.00373
Other	0.00473	0.00473

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.375
• rvis_EVS: 0.24
• rvis_percentile_EVS: 68.98

Haploinsufficiency Scores

• pHI: 0.659
• hipred: N
• hipred_score: 0.329
• ghis: 0.451

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.939

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sbds
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype

Zebrafish Information Network

• Gene name: sbds
• Affected structure: granulocyte
• Phenotype tag: abnormal
• Phenotype quality: position

Gene ontology

• Biological process: inner cell mass cell proliferation;rRNA processing;mitotic spindle organization;cell population proliferation;bone mineralization;leukocyte chemotaxis;mature ribosome assembly;bone marrow development
• Cellular component: spindle pole;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol
• Molecular function: RNA binding;protein binding;microtubule binding;rRNA binding;ribosome binding