SBDS

Chr 7

SBDS ribosome maturation factor

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

NCBI Gene: 51119 ENSG00000126524 UniProt: Q9Y3A5

This protein is required for ribosome assembly and biogenesis, working with elongation factor-like GTPase 1 to release eukaryotic initiation factor 6 from pre-ribosomal subunits to enable mature 80S ribosome formation. Mutations cause Shwachman-Bodian-Diamond syndrome, an autosomal recessive disorder characterized by pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities typically presenting in infancy. The gene is extremely intolerant of loss-of-function variants, indicating that proper protein function is essential for normal development.

GeneReviews ResearchSummary from RefSeq, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.23

Clinical Summary— SBDS

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Gene-Disease Validity (ClinGen)

Shwachman-Diamond syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

49 unique Pathogenic / Likely Pathogenic· 206 VUS of 389 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SBDS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

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?

0.59Z-score

OE missense 0.85 (0.73–1.00)

112 obs / 131.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.40–1.23)

0≤0.351.4

Missense OE?0.85 (0.73–1.00)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 8 / 11.8Missense obs/exp: 112 / 131.1Syn Z: -1.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSBDS-related Shwachman-Diamond syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6842th %ile

GOF

0.3986th %ile

LOF

0.3648th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic29

VUS206

Likely Benign102

Benign18

Conflicting10

Pathogenic

Likely Pathogenic

206

VUS

102

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	1	2	0	20
Likely Pathogenic	22	7	0	0	29
VUS	0	204	2	0	206
Likely Benign	0	1	2	99	102
Benign	0	0	15	3	18
Conflicting	—				10
Total	39	213	21	102	385

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SBDS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →