SBDS

Chr 7

SBDS ribosome maturation factor

Also known as: CGI-97, SDO1, SDS, SWDS

NCBI Gene: 51119ENSG00000126524UniProt: Q9Y3A5

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]

Primary Disease Associations & Inheritance

UniProtShwachman-Diamond syndrome 1
391
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— SBDS
🧬
Gene-Disease Validity (ClinGen)
Shwachman-Diamond syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 205 VUS of 391 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.23LOEUF
pLI 0.000
Z-score 1.02
OE 0.68 (0.40–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.59Z-score
OE missense 0.85 (0.73–1.00)
112 obs / 131.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.40–1.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.73–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 8 / 11.8Missense obs/exp: 112 / 131.1Syn Z: -1.20

ClinVar Variant Classifications

391 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic30
VUS205
Likely Benign93
Benign19
Conflicting9
35
Pathogenic
30
Likely Pathogenic
205
VUS
93
Likely Benign
19
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
1
19
0
35
Likely Pathogenic
16
7
7
0
30
VUS
0
193
12
0
205
Likely Benign
0
1
2
90
93
Benign
0
0
16
3
19
Conflicting
—9
Total312025693391

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SBDS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SBDS-related Shwachman-Diamond syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — SBDS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sleep-related breathing disorders and pulmonary hypertension.
Adir Y et al.·Eur Respir J
2021Review
Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: biological insights and clinical advances.
Reilly CR et al.·Blood
2023Review
A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.
Bluteau O et al.·Blood
2018Cohort
Shwachman-Diamond syndrome.
Dror Y·Pediatr Blood Cancer
2005Review
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation.
Lindsley RC et al.·N Engl J Med
2017
Shwachman-Diamond syndrome.
Shimamura A·Semin Hematol
2006Review
Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.
Kennedy AL et al.·Nat Commun
2021
The metabolic basis of inherited neutropenias.
Oyarbide U et al.·Br J Haematol
2024Review
Clinical and genetic spectrum of SBDS and DNAJC21 gene variants in bone marrow failure cases: Atypical and cryptic presentations.
Palla S et al.·Blood Cells Mol Dis
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Shwachman-Diamond SyndromeSDSIBMF

Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform

RECRUITING
NCT06999954Shwachman-Diamond Syndrome Alliance IncStarted 2024-02-07
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

External Resources

Links to major genomics databases and tools