SPSB2
gene geneOn this page
Also known as GRCC9SSB-2
Summary
SPSB2 (splA/ryanodine receptor domain and SOCS box containing 2, HGNC:29522) is a protein-coding gene on chromosome 12p13.31, encoding SPRY domain-containing SOCS box protein 2 (Q99619). Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
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.
Source: NCBI Gene 84727 — RefSeq curated summary.
At a glance
- GWAS associations: 2
- Clinical variants (ClinVar): 39 total — 1 pathogenic
- Druggable target: yes
- MANE Select transcript:
NM_032641
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:29522 |
| Approved symbol | SPSB2 |
| Name | splA/ryanodine receptor domain and SOCS box containing 2 |
| Location | 12p13.31 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | GRCC9, SSB-2 |
| Ensembl gene | ENSG00000111671 |
| Ensembl biotype | protein_coding |
| OMIM | 611658 |
| Entrez | 84727 |
Gene structure
Transcript identifiers
Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined
ENST00000432205, ENST00000437851, ENST00000519357, ENST00000523102, ENST00000524270, ENST00000890095, ENST00000890096, ENST00000890097, ENST00000934904, ENST00000934905, ENST00000934906, ENST00000934907, ENST00000934908, ENST00000934909, ENST00000957755, ENST00000957756
RefSeq mRNA: 3 — MANE Select: NM_032641
NM_001146316, NM_001319670, NM_032641
CCDS: CCDS8567
Canonical transcript exons
ENST00000524270 — 3 exons
| Exon | Start | End |
|---|---|---|
| ENSE00002107668 | 6872238 | 6872997 |
| ENSE00002124285 | 6870935 | 6871319 |
| ENSE00003904706 | 6873246 | 6873303 |
Expression profiles
Bgee: expression breadth ubiquitous, 195 present calls, max score 87.16.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8951 / max 153.7780, expressed in 1472 samples.
FANTOM5 promoters (2 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 129210 | 3.8632 | 1466 |
| 129209 | 0.0319 | 4 |
Top tissues by expression
237 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 87.16 | gold quality |
| right uterine tube | UBERON:0001302 | 85.26 | gold quality |
| pancreatic ductal cell | CL:0002079 | 84.35 | silver quality |
| granulocyte | CL:0000094 | 84.07 | gold quality |
| right lung | UBERON:0002167 | 82.94 | gold quality |
| right adrenal gland | UBERON:0001233 | 82.85 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 82.79 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 82.75 | gold quality |
| metanephros cortex | UBERON:0010533 | 82.70 | gold quality |
| upper lobe of lung | UBERON:0008948 | 82.60 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 82.54 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 82.28 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 82.27 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 82.15 | gold quality |
| right testis | UBERON:0004534 | 82.15 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 81.90 | gold quality |
| left adrenal gland | UBERON:0001234 | 81.79 | gold quality |
| left testis | UBERON:0004533 | 81.64 | gold quality |
| right coronary artery | UBERON:0001625 | 80.99 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 80.96 | gold quality |
| monocyte | CL:0000576 | 80.76 | gold quality |
| leukocyte | CL:0000738 | 80.74 | gold quality |
| thyroid gland | UBERON:0002046 | 80.67 | gold quality |
| kidney epithelium | UBERON:0004819 | 80.60 | gold quality |
| adrenal cortex | UBERON:0001235 | 80.50 | gold quality |
| metanephros | UBERON:0000081 | 80.36 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 80.19 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 80.12 | gold quality |
| testis | UBERON:0000473 | 79.98 | gold quality |
| left coronary artery | UBERON:0001626 | 79.95 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 6.24 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
8 targeting SPSB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-4283 | 100.00 | 66.42 | 2097 |
| HSA-MIR-185-3P | 99.95 | 67.01 | 1743 |
| HSA-MIR-19A-5P | 99.36 | 66.93 | 1675 |
| HSA-MIR-19B-1-5P | 99.36 | 67.07 | 1669 |
| HSA-MIR-19B-2-5P | 99.36 | 67.07 | 1669 |
| HSA-MIR-4291 | 99.20 | 68.88 | 2969 |
| HSA-MIR-1226-3P | 97.51 | 66.32 | 1063 |
| HSA-MIR-103B | 95.51 | 66.85 | 441 |
Literature-anchored findings (GeneRIF, showing 5)
- Shows that this gene is associated with the regulation of cell proliferation in canine mammary cancer cell lines. (PMID:19609018)
- crystal structure of SPSB2 in complex with cyclic peptide inhibitor cR8, at a resolution of 1.34 A (PMID:28549582)
- C-terminal His6 tag of the recombinant protein binds to a shallow pocket adjacent to the iNOS-binding site on a crystallographically related SPSB2 molecule (PMID:31204687)
- Results demonstrated that cellular factor SPSB2 interacts with and decreases viral protein NS5A to inhibit HCV replication. SPSBP2 interacts with the HCV protein NS5A via its SPRY domain and inhibits HCV replication by ubiquitination and degradation of NS5A. (PMID:31344133)
- Structural basis for the regulation of inducible nitric oxide synthase by the SPRY domain-containing SOCS box protein SPSB2, an E3 ubiquitin ligase. (PMID:33862200)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | SPSB2 | ENSDARG00000088985 |
| mus_musculus | Spsb2 | ENSMUSG00000038451 |
| rattus_norvegicus | Spsb2 | ENSRNOG00000015125 |
| drosophila_melanogaster | gus | FBGN0026238 |
| caenorhabditis_elegans | WBGENE00021596 | |
| caenorhabditis_elegans | WBGENE00021597 |
Paralogs (4): SPSB3 (ENSG00000162032), SPSB1 (ENSG00000171621), FBXO45 (ENSG00000174013), SPSB4 (ENSG00000175093)
Protein
Protein identifiers
SPRY domain-containing SOCS box protein 2 — Q99619 (reviewed: Q99619)
Alternative names: Gene-rich cluster protein C9
All UniProt accessions (2): Q99619, E5RIC2
UniProt curated annotations — full annotation on UniProt →
Function. Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2. Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
Subunit / interactions. Component of the probable ECS(SPSB2) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB2. Interacts with CUL5, RNF7, ELOB and ELOC. Interacts with MET. Interacts (via B30.2/SPRY domain) with PAWR; this interaction occurs in association with the Elongin BC complex. Interacts with NOS2. (Microbial infection) Interacts (via C-terminus) with HCV envelope glycoprotein E1. Interacts (via C-terminus) with HCV non-structural protein 5A; this interaction targets NS5A for ubiquitination and degradation.
Subcellular location. Cytoplasm. Cytosol.
Domain organisation. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
Pathway. Protein modification; protein ubiquitination.
Similarity. Belongs to the SPSB family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q99619-1 | 1 | yes |
| Q99619-2 | 2 |
RefSeq proteins (3): NP_001139788, NP_001306599, NP_116030* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001496 | SOCS_box | Domain |
| IPR001870 | B30.2/SPRY | Domain |
| IPR003877 | SPRY_dom | Domain |
| IPR013320 | ConA-like_dom_sf | Homologous_superfamily |
| IPR036036 | SOCS_box-like_dom_sf | Homologous_superfamily |
| IPR037340 | SSB2_SOCS | Domain |
| IPR043136 | B30.2/SPRY_sf | Homologous_superfamily |
| IPR050672 | FBXO45-Fsn/SPSB_families | Family |
Pfam: PF00622, PF07525
UniProt features (31 total): strand 16, helix 6, domain 2, turn 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1, mutagenesis site 1
Structure
Experimental structures (PDB)
9 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6JWM | X-RAY DIFFRACTION | 1.23 |
| 6KEY | X-RAY DIFFRACTION | 1.24 |
| 5XN3 | X-RAY DIFFRACTION | 1.34 |
| 6DN6 | X-RAY DIFFRACTION | 1.59 |
| 6JWN | X-RAY DIFFRACTION | 1.61 |
| 9RV5 | X-RAY DIFFRACTION | 1.75 |
| 3EMW | X-RAY DIFFRACTION | 1.8 |
| 6JKJ | X-RAY DIFFRACTION | 1.9 |
| 6DN5 | X-RAY DIFFRACTION | 2.4 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q99619-F1 | 88.40 | 0.69 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 116–119 | enhances interaction with pawr. |
Function
Pathways and Gene Ontology
Reactome pathways
7 pathways
| ID | Pathway |
|---|---|
| R-HSA-8951664 | Neddylation |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation |
| R-HSA-1280218 | Adaptive Immune System |
| R-HSA-168256 | Immune System |
| R-HSA-392499 | Metabolism of proteins |
| R-HSA-597592 | Post-translational protein modification |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation |
MSigDB gene sets: 88 (showing top):
REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KORKOLA_EMBRYONAL_CARCINOMA_UP, HNF4_DR1_Q3, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, AACTTT_UNKNOWN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS
GO Biological Process (4): ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)
GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)
GO Cellular Component (3): cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), cytoplasm (GO:0005737)
Reactome top-level categories
Rollup of top-5 pathways:
| Category | Pathways |
|---|---|
| Post-translational protein modification | 1 |
| Class I MHC mediated antigen processing & presentation | 1 |
| Immune System | 1 |
| Metabolism of proteins | 1 |
| Adaptive Immune System | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| intracellular anatomical structure | 2 |
| cellular anatomical structure | 2 |
| protein ubiquitination | 1 |
| modification-dependent protein catabolic process | 1 |
| protein modification by small protein conjugation | 1 |
| signal transduction | 1 |
| ubiquitin-dependent protein catabolic process | 1 |
| proteasomal protein catabolic process | 1 |
| enzyme-substrate adaptor activity | 1 |
| binding | 1 |
| cytoplasm | 1 |
| cullin-RING ubiquitin ligase complex | 1 |
Protein interactions and networks
STRING
586 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| SPSB2 | CISH | Q9NSE2 | 831 |
| SPSB2 | PAWR | Q96IZ0 | 514 |
| SPSB2 | SPSB3 | Q6PJ21 | 478 |
| SPSB2 | CST9L | Q9H4G1 | 453 |
| SPSB2 | CUL5 | Q93034 | 450 |
| SPSB2 | FBXL22 | Q6P050 | 396 |
| SPSB2 | FAM163A | Q96GL9 | 393 |
| SPSB2 | FBXO9 | Q9UK97 | 389 |
| SPSB2 | NT5DC2 | Q9H857 | 369 |
| SPSB2 | DYNC2I1 | Q8WVS4 | 348 |
| SPSB2 | TBCEL | Q5QJ74 | 345 |
| SPSB2 | KBTBD8 | Q8NFY9 | 344 |
| SPSB2 | FBXO2 | Q9UK22 | 339 |
| SPSB2 | ASB7 | Q9H672 | 332 |
| SPSB2 | ELOB | Q15370 | 320 |
| SPSB2 | RNF7 | Q9UBF6 | 320 |
IntAct
55 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CUL5 | SOCS2 | psi-mi:“MI:0914”(association) | 0.880 |
| SPSB2 | ELOC | psi-mi:“MI:0915”(physical association) | 0.670 |
| SPSB2 | ELOC | psi-mi:“MI:0914”(association) | 0.670 |
| SPSB2 | PAWR | psi-mi:“MI:0407”(direct interaction) | 0.590 |
| SPSB2 | PIK3R3 | psi-mi:“MI:0915”(physical association) | 0.570 |
| PIK3R3 | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.570 |
| NRF1 | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SMARCD1 | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RECK | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| FNDC3B | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SPSB2 | DMWD | psi-mi:“MI:0915”(physical association) | 0.560 |
| UBE2K | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| PRKN | SPSB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SPSB2 | PECAM1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SPSB2 | VIM | psi-mi:“MI:0915”(physical association) | 0.560 |
| SPSB2 | KIF1B | psi-mi:“MI:0915”(physical association) | 0.560 |
| SPSB2 | RNF11 | psi-mi:“MI:0915”(physical association) | 0.560 |
BioGRID (92): NOS2 (Biochemical Activity), EPHB2 (Affinity Capture-MS), TTC1 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), ARHGEF10 (Affinity Capture-MS), SPSB2 (Two-hybrid), PIK3R3 (Affinity Capture-Luminescence), EPHB2 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), TTC1 (Affinity Capture-MS), ARHGEF10 (Affinity Capture-MS), NOS2 (Co-crystal Structure), NOS2 (Reconstituted Complex), SPSB2 (Two-hybrid), SPSB2 (Two-hybrid)
ESM2 similar proteins: C0HJQ1, C0HJR3, O00182, O00214, O54891, O54974, O88838, P05162, P07583, P09382, P11116, P11762, P16045, P47929, P47967, P48538, P55345, P56470, P81184, P97590, Q1ECW6, Q29058, Q3B8N2, Q3MHZ8, Q3U7R1, Q49I35, Q5I0L3, Q5M877, Q5R7M1, Q5RAG2, Q62665, Q6DKI2, Q8BNV1, Q8BYL4, Q8IXI1, Q8JZN7, Q8K2J0, Q8K419, Q8N3E9, Q8TCE9
Diamond homologs: A1Z6E0, A8QGZ7, A8XT88, B0X9V1, B3MDR0, B3NRP1, B4F739, B4GBN7, B4HQ29, B4J6Q0, B4KNC5, B4LMQ3, B4MR59, B4P4K8, B4QE02, O88838, P0C2W1, P0CH38, Q16XV7, Q18223, Q28DT9, Q290L5, Q5E9X6, Q5M877, Q6NZ03, Q7QGL9, Q7ZXY1, Q8K3B1, Q8R5B6, Q96A44, Q96BD6, Q99619, Q9D5L7, Q9V6L9, Q3ZBA7, Q8N3Y1, Q3MHZ2, Q571F5, Q6PJ21, Q3SX45
SIGNOR signaling
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| SPSB2 | “up-regulates activity” | “Elongin E3-Cul-5” | binding |
| SPSB2 | “down-regulates quantity by destabilization” | NANOS2 | binding |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Antigen processing: Ubiquitination & Proteasome degradation | 6 | 11.8× | 7e-04 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| ubiquitin-dependent protein catabolic process | 5 | 16.9× | 1e-03 |
| protein ubiquitination | 6 | 11.3× | 1e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
39 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 27 |
| Likely benign | 1 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 625810 | GRCh37/hg19 12p13.33-13.31(chr12:237588-8278292) | Pathogenic |
SpliceAI
437 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 12:6871318:CG:C | acceptor_gain | 1.0000 |
| 12:6871320:C:CC | acceptor_gain | 1.0000 |
| 12:6871315:CTCCG:C | acceptor_gain | 0.9900 |
| 12:6871316:TCCG:T | acceptor_gain | 0.9900 |
| 12:6871317:CCG:C | acceptor_gain | 0.9900 |
| 12:6871317:CCGC:C | acceptor_gain | 0.9900 |
| 12:6871318:CGC:C | acceptor_gain | 0.9900 |
| 12:6872720:T:TA | donor_gain | 0.9900 |
| 12:6873213:A:AC | donor_gain | 0.9900 |
| 12:6873214:C:CC | donor_gain | 0.9900 |
| 12:6873257:T:TA | donor_gain | 0.9900 |
| 12:6872294:A:AC | donor_gain | 0.9800 |
| 12:6872295:C:CC | donor_gain | 0.9800 |
| 12:6872716:T:TA | donor_gain | 0.9800 |
| 12:6873258:C:A | donor_gain | 0.9800 |
| 12:6871318:C:T | acceptor_gain | 0.9700 |
| 12:6872711:A:AT | donor_gain | 0.9700 |
| 12:6872724:TG:T | donor_gain | 0.9700 |
| 12:6872924:C:CA | donor_gain | 0.9700 |
| 12:6872925:C:A | donor_gain | 0.9700 |
| 12:6871316:TCCGC:T | acceptor_loss | 0.9600 |
| 12:6871319:GCTG:G | acceptor_loss | 0.9600 |
| 12:6871320:C:CA | acceptor_loss | 0.9600 |
| 12:6871321:T:A | acceptor_loss | 0.9600 |
| 12:6872723:TTG:T | donor_gain | 0.9600 |
| 12:6873138:G:A | donor_gain | 0.9600 |
| 12:6871316:TCC:T | acceptor_gain | 0.9500 |
| 12:6873094:C:A | donor_gain | 0.9500 |
| 12:6873217:G:A | donor_gain | 0.9500 |
| 12:6872294:ACTG:A | donor_gain | 0.9400 |
AlphaMissense
1659 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 12:6872760:A:G | W48R | 0.998 |
| 12:6872760:A:T | W48R | 0.998 |
| 12:6872758:C:A | W48C | 0.997 |
| 12:6872758:C:G | W48C | 0.997 |
| 12:6872290:G:C | S204R | 0.996 |
| 12:6872290:G:T | S204R | 0.996 |
| 12:6872292:T:G | S204R | 0.996 |
| 12:6872514:A:G | S130P | 0.995 |
| 12:6872631:A:G | W91R | 0.995 |
| 12:6872631:A:T | W91R | 0.995 |
| 12:6872759:C:G | W48S | 0.995 |
| 12:6872505:A:G | W133R | 0.994 |
| 12:6872505:A:T | W133R | 0.994 |
| 12:6872678:G:A | T75I | 0.994 |
| 12:6872619:A:G | W95R | 0.993 |
| 12:6872619:A:T | W95R | 0.993 |
| 12:6872577:C:G | A109P | 0.992 |
| 12:6872629:C:A | W91C | 0.992 |
| 12:6872629:C:G | W91C | 0.992 |
| 12:6872272:G:C | C210W | 0.988 |
| 12:6872503:C:A | W133C | 0.988 |
| 12:6872503:C:G | W133C | 0.988 |
| 12:6872591:G:T | A104D | 0.988 |
| 12:6872329:G:C | F191L | 0.987 |
| 12:6872329:G:T | F191L | 0.987 |
| 12:6872331:A:G | F191L | 0.987 |
| 12:6872529:C:G | G125R | 0.987 |
| 12:6872583:C:G | G107R | 0.987 |
| 12:6872364:A:C | Y180D | 0.986 |
| 12:6872504:C:G | W133S | 0.986 |
dbSNP variants (sampled 300 via entrez): RS1000452414 (12:6871110 G>A), RS1000867947 (12:6875208 T>C), RS1000885016 (12:6870999 G>A,T), RS1001711110 (12:6871422 G>A), RS1002698256 (12:6870534 A>G), RS1003736385 (12:6871238 G>A,C), RS1004190125 (12:6873350 G>A), RS1006668487 (12:6874780 T>A,C), RS1008870100 (12:6870979 T>C), RS1010333975 (12:6871175 C>T), RS1010366451 (12:6871011 G>A), RS1011006526 (12:6873528 C>A), RS1012900627 (12:6872722 C>T), RS1013972042 (12:6874259 C>T), RS1014357934 (12:6873858 T>C,G)
Disease associations
OMIM: gene MIM:611658 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
2 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST003799_9 | Colorectal cancer | 4.000000e-11 |
| GCST010002_206 | Refractive error | 3.000000e-62 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL3325308 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB clinical annotations
1 annotations.
| Variant | Type | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs12302749 | Efficacy | 3 | methylphenidate | Attention Deficit Disorder with Hyperactivity |
ChEMBL bioactivities
3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.36 | Kd | 4.4 | nM | CHEMBL3326273 |
| 7.46 | Kd | 35.1 | nM | CHEMBL3326275 |
| 6.50 | Kd | 318 | nM | CHEMBL3326274 |
PubChem BioAssay actives
3 with measured affinity, of 22 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 2-[(4S,7S,10S,13S,16S,19S,22S,25R)-25-acetamido-7,10,13-tris(2-amino-2-oxoethyl)-16-[(2S)-butan-2-yl]-4-carbamoyl-6,9,12,15,18,21,24-heptaoxo-22-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacos-19-yl]acetic acid | 1185937: Binding affinity to GST-tagged SPSB2 (unknown origin) expressed in Escherichia coli BL21 (DE3) by SPR assay | kd | 0.0044 | uM |
| (3S)-3-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-4-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid | 1185937: Binding affinity to GST-tagged SPSB2 (unknown origin) expressed in Escherichia coli BL21 (DE3) by SPR assay | kd | 0.0351 | uM |
| (3S)-3-acetamido-4-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid | 1185937: Binding affinity to GST-tagged SPSB2 (unknown origin) expressed in Escherichia coli BL21 (DE3) by SPR assay | kd | 0.3180 | uM |
CTD chemical–gene interactions
24 total (human), top 24 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | increases expression, affects expression, affects cotreatment | 3 |
| bisphenol A | increases methylation | 1 |
| decabromobiphenyl ether | affects expression | 1 |
| sodium arsenite | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| ICG 001 | increases expression | 1 |
| jinfukang | affects cotreatment, increases expression | 1 |
| Atrazine | increases expression | 1 |
| Benzo(a)pyrene | increases expression | 1 |
| Cisplatin | affects cotreatment, increases expression | 1 |
| Diazinon | increases methylation | 1 |
| Formaldehyde | decreases expression | 1 |
| Hydralazine | increases expression, affects cotreatment | 1 |
| Hydrogen Peroxide | affects expression | 1 |
| Methyl Methanesulfonate | increases expression | 1 |
| Oxygen | decreases expression | 1 |
| Smoke | decreases expression | 1 |
| Thiram | increases expression | 1 |
| Tobacco Smoke Pollution | decreases expression | 1 |
| Tretinoin | increases expression | 1 |
| Urethane | decreases expression | 1 |
| Copper Sulfate | decreases expression | 1 |
| Acrylamide | increases expression | 1 |
| Vitamin K 3 | affects expression | 1 |
ChEMBL screening assays
3 unique, capped per target: 3 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL3363657 | Binding | Binding affinity to GST-tagged SPSB2 (unknown origin) expressed in Escherichia coli BL21 (DE3) by SPR assay | A potent cyclic peptide targeting SPSB2 protein as a potential anti-infective agent. — J Med Chem |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.