SPSB2

Chr 12

splA/ryanodine receptor domain and SOCS box containing 2

Also known as: GRCC9, SSB2

NCBI Gene: 84727ENSG00000111671UniProt: Q99619

This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Research Assistant →
0
Active trials
4
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
1.00
LOEUF
DN
Mechanism· predicted
Clinical Summary— SPSB2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 58 VUS of 115 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.021
Z-score 1.58
OE 0.44 (0.21–1.00)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.61Z-score
OE missense 1.14 (1.01–1.29)
172 obs / 150.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.44 (0.21–1.00)
0≤0.351.4
Missense OE1.14 (1.01–1.29)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 4 / 9.1Missense obs/exp: 172 / 150.9Syn Z: -0.22
DN
0.6647th %ile
GOF
0.6248th %ile
LOF
0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic2
VUS58
Likely Benign1
Benign1
43
Pathogenic
2
Likely Pathogenic
58
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
2
0
2
VUS
0
45
13
0
58
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Total045600105

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

View in ClinVar →

Protein Context — Lollipop Plot

SPSB2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients