SSU72
gene geneOn this page
Also known as HSPC182
Summary
SSU72 (SSU72 homolog, RNA polymerase II CTD phosphatase, HGNC:25016) is a protein-coding gene on chromosome 1p36.33, encoding RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (Q9NP77). Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).
Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in co-transcriptional mRNA 3’-end processing, cleavage and polyadenylation pathway. Located in cytosol and nucleoplasm.
Source: NCBI Gene 29101 — RefSeq curated summary.
At a glance
- GWAS associations: 1
- Clinical variants (ClinVar): 20 total — 1 pathogenic
- Druggable target: yes
- Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
- MANE Select transcript:
NM_014188
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:25016 |
| Approved symbol | SSU72 |
| Name | SSU72 homolog, RNA polymerase II CTD phosphatase |
| Location | 1p36.33 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | HSPC182 |
| Ensembl gene | ENSG00000160075 |
| Ensembl biotype | protein_coding |
| OMIM | 617680 |
| Entrez | 29101 |
Gene structure
Transcript identifiers
Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron
ENST00000291386, ENST00000359060, ENST00000378725, ENST00000378726, ENST00000851386, ENST00000851387, ENST00000851388, ENST00000929201, ENST00000929202
RefSeq mRNA: 1 — MANE Select: NM_014188
NM_014188
CCDS: CCDS32
Canonical transcript exons
ENST00000291386 — 5 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001049594 | 1544863 | 1545002 |
| ENSE00001478524 | 1574478 | 1574863 |
| ENSE00001824181 | 1541673 | 1542167 |
| ENSE00003470831 | 1564773 | 1564916 |
| ENSE00003590028 | 1543869 | 1543987 |
Expression profiles
Bgee: expression breadth ubiquitous, 256 present calls, max score 98.84.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 150.0128 / max 716.7235, expressed in 1828 samples.
FANTOM5 promoters (9 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 9803 | 98.8398 | 1828 |
| 9802 | 33.0765 | 1823 |
| 9801 | 17.7135 | 1816 |
| 9793 | 0.1599 | 57 |
| 9796 | 0.0972 | 13 |
| 9797 | 0.0949 | 9 |
| 9798 | 0.0140 | 5 |
| 9795 | 0.0127 | 5 |
| 9794 | 0.0042 | 3 |
Top tissues by expression
256 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| parotid gland | UBERON:0001831 | 98.84 | gold quality |
| gastrocnemius | UBERON:0001388 | 98.27 | gold quality |
| muscle of leg | UBERON:0001383 | 98.03 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 97.95 | gold quality |
| gingival epithelium | UBERON:0001949 | 97.84 | gold quality |
| right frontal lobe | UBERON:0002810 | 97.74 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 97.70 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 97.70 | gold quality |
| gingiva | UBERON:0001828 | 97.68 | gold quality |
| apex of heart | UBERON:0002098 | 97.65 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 97.64 | gold quality |
| pancreatic ductal cell | CL:0002079 | 97.63 | gold quality |
| Brodmann (1909) area 23 | UBERON:0013554 | 97.60 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 97.54 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 97.53 | gold quality |
| caudate nucleus | UBERON:0001873 | 97.52 | gold quality |
| adenohypophysis | UBERON:0002196 | 97.51 | gold quality |
| thyroid gland | UBERON:0002046 | 97.44 | gold quality |
| nucleus accumbens | UBERON:0001882 | 97.43 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 97.41 | gold quality |
| primary visual cortex | UBERON:0002436 | 97.39 | gold quality |
| putamen | UBERON:0001874 | 97.37 | gold quality |
| right atrium auricular region | UBERON:0006631 | 97.33 | gold quality |
| esophagus mucosa | UBERON:0002469 | 97.29 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 97.29 | gold quality |
| prefrontal cortex | UBERON:0000451 | 97.24 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 97.22 | gold quality |
| quadriceps femoris | UBERON:0001377 | 97.19 | gold quality |
| oviduct epithelium | UBERON:0004804 | 97.19 | gold quality |
| pituitary gland | UBERON:0000007 | 97.18 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
46 targeting SSU72, 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-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-1252-5P | 100.00 | 69.80 | 2774 |
| HSA-MIR-103A-3P | 99.98 | 69.14 | 1595 |
| HSA-MIR-107 | 99.98 | 69.14 | 1595 |
| HSA-MIR-3148 | 99.97 | 75.06 | 6478 |
| HSA-MIR-548AJ-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548X-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-651-3P | 99.94 | 73.48 | 5177 |
| HSA-MIR-548J-3P | 99.94 | 72.61 | 4881 |
| HSA-MIR-548AE-3P | 99.93 | 72.66 | 4867 |
| HSA-MIR-548AH-3P | 99.93 | 72.54 | 4872 |
| HSA-MIR-548AM-3P | 99.93 | 72.54 | 4872 |
| HSA-MIR-548AQ-3P | 99.93 | 72.66 | 4867 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-589-3P | 99.91 | 69.62 | 2088 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-548D-3P | 99.87 | 70.67 | 4362 |
| HSA-MIR-6124 | 99.87 | 69.78 | 3551 |
| HSA-MIR-548BB-3P | 99.86 | 70.58 | 4354 |
| HSA-MIR-659-3P | 99.85 | 70.69 | 1620 |
| HSA-MIR-4728-5P | 99.85 | 69.39 | 4718 |
| HSA-MIR-548AC | 99.84 | 70.77 | 4351 |
| HSA-MIR-548H-3P | 99.84 | 70.80 | 4349 |
| HSA-MIR-548Z | 99.84 | 70.80 | 4349 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.
Literature-anchored findings (GeneRIF, showing 9)
- Molecular cloning and characterization of functions of human ssu72. (PMID:15659578)
- Data suggest that Ssu72 is a novel cohesin-binding protein capable of regulating cohesion between sister chromatid arms. (PMID:20818333)
- crystal structure at 2.4 A resolution of the amino-terminal domain (residues 30-340) of human symplekin in a ternary complex with the Pol II carboxy-terminal domain (CTD) Ser 5 phosphatase Ssu72 and a CTD Ser 5 phosphopeptide (PMID:20861839)
- The pSer7 phosphatase activity of Ssu72 is approximately 4000-fold lower than its pSer5 phosphatase activity toward a peptide substrate (PMID:23070812)
- Aurora B kinase directly targets Ssu72 phosphatase for regulation of sister chromatid cohesion during early mitosis. (PMID:24149858)
- a hand-off model in which Ssu72 mediates a conformational transition in TFIIB, accounting for the role of Ssu72 in transcription reinitiation, gene looping, and promoter-terminator cross-talk. (PMID:29158257)
- results demonstrate when Ssu72 can act on early transcription complexes and suggest that Ssu72 may also function in thepreinitiation complex prior to initiation. (PMID:30901332)
- Diverse and conserved roles of the protein Ssu72 in eukaryotes: from yeast to higher organisms. (PMID:33244642)
- Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases. (PMID:33917542)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ssu72 | ENSDARG00000031216 |
| mus_musculus | Ssu72 | ENSMUSG00000029038 |
| rattus_norvegicus | Ssu72 | ENSRNOG00000017829 |
| drosophila_melanogaster | Ssu72 | FBGN0031054 |
| caenorhabditis_elegans | WBGENE00020480 |
Paralogs (6): SSU72L6 (ENSG00000230268), SSU72L4 (ENSG00000283873), SSU72L5 (ENSG00000284018), SSU72L2 (ENSG00000284306), SSU72L1 (ENSG00000284438), SSU72L3 (ENSG00000284546)
Protein
Protein identifiers
RNA polymerase II subunit A C-terminal domain phosphatase SSU72 — Q9NP77 (reviewed: Q9NP77)
All UniProt accessions (1): Q9NP77
UniProt curated annotations — full annotation on UniProt →
Function. Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. Plays a role in pre-mRNA polyadenylation via its interaction with SYMPK.
Subunit / interactions. Interacts with GTF2B (via C-terminus); this interaction is inhibited by SYMPK. Interacts with RB1. Interacts with CD226. Interacts with SYMPK.
Subcellular location. Nucleus. Cytoplasm.
Similarity. Belongs to the SSU72 phosphatase family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9NP77-1 | 1 | yes |
| Q9NP77-2 | 2 |
RefSeq proteins (1): NP_054907* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR006811 | RNA_pol_II_suA | Family |
Pfam: PF04722
Catalyzed reactions (Rhea), 2 shown:
- O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
- O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)
UniProt features (19 total): helix 7, strand 7, chain 1, coiled-coil region 1, splice variant 1, mutagenesis site 1, sequence conflict 1
Structure
Experimental structures (PDB)
4 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4H3K | X-RAY DIFFRACTION | 2 |
| 4H3H | X-RAY DIFFRACTION | 2.2 |
| 3O2Q | X-RAY DIFFRACTION | 2.4 |
| 3O2S | X-RAY DIFFRACTION | 2.5 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9NP77-F1 | 95.85 | 0.94 |
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 |
|---|---|
| 12 | abolishes phosphatase activity. |
Function
Pathways and Gene Ontology
Reactome pathways
3 pathways
| ID | Pathway |
|---|---|
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes |
| R-HSA-73857 | RNA Polymerase II Transcription |
| R-HSA-74160 | Gene expression (Transcription) |
MSigDB gene sets: 132 (showing top):
E2F_Q4_01, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_MRNA_3_END_PROCESSING, GARY_CD5_TARGETS_DN, GOBP_TERMINATION_OF_RNA_POLYMERASE_II_TRANSCRIPTION, FUJII_YBX1_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS
GO Biological Process (5): termination of RNA polymerase II transcription (GO:0006369), co-transcriptional mRNA 3’-end processing, cleavage and polyadenylation pathway (GO:0180010), regulation of transcription by RNA polymerase II (GO:0006357), mRNA processing (GO:0006397), mRNA 3’-end processing (GO:0031124)
GO Molecular Function (5): RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787)
GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), nucleus (GO:0005634), cytoplasm (GO:0005737)
Reactome top-level categories
Rollup of top-2 pathways:
| Category | Pathways |
|---|---|
| RNA Polymerase II Transcription | 1 |
| Gene expression (Transcription) | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| transcription by RNA polymerase II | 2 |
| DNA-templated transcription termination | 1 |
| mRNA 3’-end processing | 1 |
| co-transcriptional RNA 3’-end processing, cleavage and polyadenylation pathway | 1 |
| regulation of DNA-templated transcription | 1 |
| RNA processing | 1 |
| mRNA metabolic process | 1 |
| mRNA processing | 1 |
| RNA 3’-end processing | 1 |
| protein serine/threonine phosphatase activity | 1 |
| RNA polymerase II CTD heptapeptide repeat modifying activity | 1 |
| phosphatase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| phosphoprotein phosphatase activity | 1 |
| binding | 1 |
| catalytic activity | 1 |
| nuclear lumen | 1 |
| cytoplasm | 1 |
| mRNA cleavage factor complex | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular anatomical structure | 1 |
Protein interactions and networks
STRING
1812 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| SSU72 | WDR82 | Q6UXN9 | 980 |
| SSU72 | GTF2B | Q00403 | 936 |
| SSU72 | CPSF3 | Q9UKF6 | 885 |
| SSU72 | PCF11 | O94913 | 873 |
| SSU72 | SYMPK | Q92797 | 861 |
| SSU72 | CTDP1 | Q9Y5B0 | 821 |
| SSU72 | RPAP2 | Q8IXW5 | 810 |
| SSU72 | EEF1A1 | P04719 | 798 |
| SSU72 | POLR2B | P30876 | 787 |
| SSU72 | SUPT5H | O00267 | 774 |
| SSU72 | CD226 | Q15762 | 745 |
| SSU72 | CPSF2 | Q9P2I0 | 717 |
| SSU72 | CSTF2 | P33240 | 714 |
| SSU72 | WDR33 | Q9C0J8 | 705 |
| SSU72 | POLR2A | P24928 | 638 |
IntAct
27 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| RAD21 | STAG2 | psi-mi:“MI:0914”(association) | 0.970 |
| RAD21 | SMC1A | psi-mi:“MI:0914”(association) | 0.930 |
| SSU72 | RAD21 | psi-mi:“MI:0915”(physical association) | 0.670 |
| SSU72 | RAD21 | psi-mi:“MI:0914”(association) | 0.670 |
| RAD21 | SSU72 | psi-mi:“MI:0407”(direct interaction) | 0.670 |
| SSU72 | RAD21 | psi-mi:“MI:0403”(colocalization) | 0.670 |
| STAG2 | SSU72 | psi-mi:“MI:0407”(direct interaction) | 0.580 |
| HTT | SSU72 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CPSF6 | DDX39A | psi-mi:“MI:0914”(association) | 0.480 |
| MAPK8 | SSU72 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SSU72 | MAPK9 | psi-mi:“MI:0915”(physical association) | 0.370 |
| FOS | TRAPPC13 | psi-mi:“MI:0914”(association) | 0.350 |
| RRP1B | ZNF785 | psi-mi:“MI:0914”(association) | 0.350 |
| UIMC1 | PYCR3 | psi-mi:“MI:0914”(association) | 0.350 |
| SSU72 | HNRNPL | psi-mi:“MI:0914”(association) | 0.350 |
| SPANXN4 | UBA6 | psi-mi:“MI:0914”(association) | 0.350 |
| EN1 | MEIS1 | psi-mi:“MI:0914”(association) | 0.350 |
| PRM3 | ARRB2 | psi-mi:“MI:0914”(association) | 0.350 |
| POU3F1 | DUSP3 | psi-mi:“MI:0914”(association) | 0.350 |
| EPB41L5 | LIN7A | psi-mi:“MI:0914”(association) | 0.350 |
| SSU72 | PCF11 | psi-mi:“MI:2364”(proximity) | 0.270 |
BioGRID (79): SSU72 (Co-fractionation), SSU72 (Co-fractionation), SSU72 (Co-fractionation), SSU72 (Co-fractionation), SSU72 (Co-fractionation), SSU72 (Affinity Capture-MS), CPSF1 (Affinity Capture-MS), CPSF2 (Affinity Capture-MS), CPSF3 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF3 (Affinity Capture-MS), HIST2H2AA4 (Affinity Capture-MS), HNRNPL (Affinity Capture-MS), SYMPK (Affinity Capture-MS), CDKN2AIP (Proximity Label-MS)
ESM2 similar proteins: A0JN27, A6H7F7, B2RYU6, B5FXJ6, B5FYY5, B5X7X4, F1LTR1, F6RQL9, O14787, O43504, P22234, P61201, P61202, P61203, Q13126, Q13888, Q17QI2, Q2TBV5, Q2YDH6, Q3SZ68, Q3T132, Q4KLK9, Q4R9A8, Q4VC33, Q5F398, Q5R532, Q5RKJ1, Q5SP67, Q5ZJQ7, Q63ZJ2, Q66X52, Q6DEG4, Q6DF40, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7ZXB7, Q92572, Q99LG2
Diamond homologs: A0A1W2PQ27, A0A1W2PQ64, A0A1W2PQC6, A0A1W2PQD8, A0A1W2PQJ5, A0A1W2PR75, O42868, P0CR76, P0CR77, P53538, Q17QI2, Q22453, Q2HFZ9, Q2UPU5, Q4IPC8, Q4KLK9, Q4WHY5, Q558Z3, Q5ZJQ7, Q6BYP7, Q6C195, Q6CQ61, Q6FMU7, Q6NRQ7, Q6PC19, Q75E60, Q7SFY0, Q9CY97, Q9NP77
SIGNOR signaling
27 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| SSU72 | “up-regulates activity” | POLR2A | dephosphorylation |
| AURKB | “down-regulates quantity by destabilization” | SSU72 | phosphorylation |
| AURKB | “down-regulates activity” | SSU72 | phosphorylation |
| SSU72 | “up-regulates activity” | STAG2 | dephosphorylation |
Disease & clinical
Clinical variants and AI predictions
ClinVar
20 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 12 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1328099 | GRCh37/hg19 1p36.33-36.32(chr1:753552-4034574)x1 | Pathogenic |
SpliceAI
1343 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:1542168:C:CC | acceptor_gain | 1.0000 |
| 1:1542168:CTGC:C | acceptor_loss | 1.0000 |
| 1:1543863:ACTT:A | donor_loss | 1.0000 |
| 1:1543867:A:AC | donor_gain | 1.0000 |
| 1:1543867:A:T | donor_loss | 1.0000 |
| 1:1543868:C:CC | donor_gain | 1.0000 |
| 1:1543868:CA:C | donor_gain | 1.0000 |
| 1:1543868:CACA:C | donor_gain | 1.0000 |
| 1:1543983:CAGAT:C | acceptor_gain | 1.0000 |
| 1:1543984:AGAT:A | acceptor_gain | 1.0000 |
| 1:1543986:AT:A | acceptor_gain | 1.0000 |
| 1:1543988:C:CC | acceptor_gain | 1.0000 |
| 1:1543988:C:T | acceptor_loss | 1.0000 |
| 1:1543989:T:G | acceptor_loss | 1.0000 |
| 1:1552031:C:A | donor_gain | 1.0000 |
| 1:1564786:T:A | donor_gain | 1.0000 |
| 1:1564805:CAT:C | donor_gain | 1.0000 |
| 1:1564917:C:CC | acceptor_gain | 1.0000 |
| 1:1542163:TGGAT:T | acceptor_gain | 0.9900 |
| 1:1542165:GAT:G | acceptor_gain | 0.9900 |
| 1:1542166:AT:A | acceptor_gain | 0.9900 |
| 1:1543862:TAC:T | donor_loss | 0.9900 |
| 1:1543865:TTA:T | donor_gain | 0.9900 |
| 1:1543865:TTACA:T | donor_gain | 0.9900 |
| 1:1543866:TAC:T | donor_gain | 0.9900 |
| 1:1543866:TACAC:T | donor_gain | 0.9900 |
| 1:1543867:ACA:A | donor_gain | 0.9900 |
| 1:1543867:ACACA:A | donor_gain | 0.9900 |
| 1:1543868:CAC:C | donor_gain | 0.9900 |
| 1:1543868:CACAC:C | donor_gain | 0.9900 |
AlphaMissense
1299 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:1543897:G:T | A152E | 1.000 |
| 1:1543900:C:T | G151E | 1.000 |
| 1:1543901:C:A | G151W | 1.000 |
| 1:1543901:C:G | G151R | 1.000 |
| 1:1543901:C:T | G151R | 1.000 |
| 1:1543909:G:T | A148D | 1.000 |
| 1:1543910:C:G | A148P | 1.000 |
| 1:1543923:G:C | D143E | 1.000 |
| 1:1543923:G:T | D143E | 1.000 |
| 1:1543924:T:A | D143V | 1.000 |
| 1:1543924:T:C | D143G | 1.000 |
| 1:1543924:T:G | D143A | 1.000 |
| 1:1543925:C:A | D143Y | 1.000 |
| 1:1543925:C:G | D143H | 1.000 |
| 1:1543925:C:T | D143N | 1.000 |
| 1:1543938:A:C | N138K | 1.000 |
| 1:1543938:A:T | N138K | 1.000 |
| 1:1543945:A:T | V136E | 1.000 |
| 1:1544894:G:C | C111W | 1.000 |
| 1:1544895:C:T | C111Y | 1.000 |
| 1:1544934:A:G | F98S | 1.000 |
| 1:1544943:G:T | P95Q | 1.000 |
| 1:1544944:G:A | P95S | 1.000 |
| 1:1544951:C:A | K92N | 1.000 |
| 1:1544951:C:G | K92N | 1.000 |
| 1:1544953:T:C | K92E | 1.000 |
| 1:1544963:A:C | N88K | 1.000 |
| 1:1544963:A:T | N88K | 1.000 |
| 1:1544966:T:A | R87S | 1.000 |
| 1:1544966:T:G | R87S | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000033034 (1:1573494 G>A,C), RS1000033620 (1:1559802 C>T), RS1000143929 (1:1558293 G>C), RS1000209096 (1:1555670 C>A), RS1000224402 (1:1542576 A>G), RS1000254452 (1:1553996 G>A,C), RS1000278304 (1:1542792 A>C), RS1000333653 (1:1564351 A>C,T), RS1000340266 (1:1568539 G>A), RS1000363165 (1:1558090 T>C), RS1000384168 (1:1573684 T>C), RS1000497265 (1:1557238 T>A,C,G), RS1000515570 (1:1546488 A>C,T), RS1000613929 (1:1541939 A>G), RS1000715530 (1:1556985 T>C)
Disease associations
OMIM: gene MIM:617680 | disease phenotypes: MIM:611490
GenCC curated gene-disease
Mondo (1): autosomal recessive osteopetrosis 4 (MONDO:0012676)
Orphanet (1): Autosomal recessive malignant osteopetrosis (Orphanet:667)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
1 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST005951_34 | Body mass index | 3.000000e-08 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004340 | body mass index |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| C566933 | Osteopetrosis, Autosomal Recessive 4 (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL3317331 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
Binding affinities (BindingDB)
1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid | IC50 | 2900 nM | US-9522881: Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) |
ChEMBL bioactivities
1 potent at pChembl≥5 of 4 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 5.89 | IC50 | 1300 | nM | CHEMBL3319356 |
PubChem BioAssay actives
1 with measured affinity, of 13 total; 1 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 |
|---|---|---|---|---|
| 6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid | 1182545: Inhibition of Ssu72 (unknown origin) | ic50 | 1.3000 | uM |
CTD chemical–gene interactions
33 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects cotreatment, increases expression, increases methylation | 5 |
| bisphenol A | increases methylation, increases expression, affects cotreatment | 2 |
| sodium arsenite | decreases expression | 2 |
| bisphenol F | affects cotreatment, increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| monomethylarsonous acid | decreases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, increases expression | 1 |
| ICG 001 | increases expression | 1 |
| Grape Seed Proanthocyanidins | affects cotreatment, increases expression | 1 |
| dorsomorphin | increases expression, affects cotreatment | 1 |
| eprenetapopt | affects expression, affects reaction | 1 |
| Sunitinib | increases expression | 1 |
| Fulvestrant | affects cotreatment, increases methylation | 1 |
| Acetaminophen | increases expression | 1 |
| Air Pollutants | increases expression, increases abundance | 1 |
| Arsenic | affects expression, affects methylation | 1 |
| Catechin | increases expression, affects cotreatment | 1 |
| Dexamethasone | affects cotreatment, increases expression | 1 |
| Doxorubicin | increases expression | 1 |
| Indomethacin | affects cotreatment, increases expression | 1 |
| Ivermectin | decreases expression | 1 |
| Methyl Methanesulfonate | decreases expression | 1 |
| Phthalic Acids | increases methylation | 1 |
| Rotenone | decreases expression | 1 |
| Smoke | decreases expression | 1 |
| Tobacco Smoke Pollution | increases expression | 1 |
| 1-Methyl-3-isobutylxanthine | affects cotreatment, increases expression | 1 |
| Cyclosporine | decreases expression | 1 |
| Sodium Selenite | increases 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 |
|---|---|---|---|
| CHEMBL3369287 | Binding | Inhibition of Ssu72 (unknown origin) | Therapeutic potential of targeting the oncogenic SHP2 phosphatase. — J Med Chem |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): autosomal recessive osteopetrosis 4