CMBL
gene geneOn this page
Also known as FLJ23617
Summary
CMBL (carboxymethylenebutenolidase homolog, HGNC:25090) is a protein-coding gene on chromosome 5p15.2, encoding Carboxymethylenebutenolidase homolog (Q96DG6). Cysteine hydrolase whose endogenous substrates and physiological function are unknown.
CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase family that is highly expressed in liver cytosol. CMBL preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al., 2010 [PubMed 20177059]).
Source: NCBI Gene 134147 — RefSeq curated summary.
At a glance
- GWAS associations: 1
- Clinical variants (ClinVar): 62 total — 2 pathogenic
- Druggable target: yes
- MANE Select transcript:
NM_138809
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:25090 |
| Approved symbol | CMBL |
| Name | carboxymethylenebutenolidase homolog |
| Location | 5p15.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | FLJ23617 |
| Ensembl gene | ENSG00000164237 |
| Ensembl biotype | protein_coding |
| OMIM | 613379 |
| Entrez | 134147 |
Gene structure
Transcript identifiers
Ensembl transcripts: 27 — 21 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron
ENST00000296658, ENST00000503834, ENST00000506224, ENST00000506821, ENST00000510532, ENST00000511963, ENST00000514202, ENST00000873539, ENST00000873540, ENST00000873541, ENST00000873542, ENST00000873543, ENST00000873544, ENST00000873545, ENST00000873546, ENST00000873547, ENST00000873548, ENST00000873549, ENST00000873550, ENST00000873551, ENST00000873552, ENST00000873553, ENST00000873554, ENST00000873555, ENST00000873556, ENST00000873557, ENST00000941395
RefSeq mRNA: 1 — MANE Select: NM_138809
NM_138809
CCDS: CCDS3878
Canonical transcript exons
ENST00000296658 — 6 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001266385 | 10277595 | 10280632 |
| ENSE00001315089 | 10307625 | 10307902 |
| ENSE00003475769 | 10290548 | 10290781 |
| ENSE00003501504 | 10286354 | 10286496 |
| ENSE00003510720 | 10282197 | 10282288 |
| ENSE00003603908 | 10288422 | 10288529 |
Expression profiles
Bgee: expression breadth ubiquitous, 252 present calls, max score 99.85.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2050 / max 385.0840, expressed in 1530 samples.
FANTOM5 promoters (9 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 60890 | 16.6116 | 1508 |
| 60889 | 4.5055 | 1325 |
| 60888 | 1.1975 | 451 |
| 60893 | 0.8309 | 453 |
| 60894 | 0.3017 | 157 |
| 60891 | 0.2688 | 127 |
| 60887 | 0.2047 | 96 |
| 60892 | 0.1454 | 50 |
| 60886 | 0.1390 | 45 |
Top tissues by expression
257 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| kidney epithelium | UBERON:0004819 | 99.85 | gold quality |
| ileal mucosa | UBERON:0000331 | 99.70 | gold quality |
| jejunal mucosa | UBERON:0000399 | 99.58 | gold quality |
| vastus lateralis | UBERON:0001379 | 99.16 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 98.67 | gold quality |
| biceps brachii | UBERON:0001507 | 98.59 | gold quality |
| jejunum | UBERON:0002115 | 98.51 | gold quality |
| duodenum | UBERON:0002114 | 98.27 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 98.21 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 97.96 | gold quality |
| quadriceps femoris | UBERON:0001377 | 97.86 | gold quality |
| colonic mucosa | UBERON:0000317 | 97.51 | gold quality |
| renal medulla | UBERON:0000362 | 97.15 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 96.97 | gold quality |
| deltoid | UBERON:0001476 | 96.95 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 96.90 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 96.82 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 96.76 | gold quality |
| adult organism | UBERON:0007023 | 96.58 | gold quality |
| rectum | UBERON:0001052 | 96.42 | gold quality |
| muscle tissue | UBERON:0002385 | 96.36 | gold quality |
| muscle organ | UBERON:0001630 | 96.12 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 95.96 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 95.92 | gold quality |
| gastrocnemius | UBERON:0001388 | 95.86 | gold quality |
| liver | UBERON:0002107 | 95.82 | gold quality |
| pancreatic ductal cell | CL:0002079 | 95.78 | gold quality |
| muscle of leg | UBERON:0001383 | 95.62 | gold quality |
| kidney | UBERON:0002113 | 95.35 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 94.15 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 13.92 |
| E-CURD-88 | no | 504.93 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
67 targeting CMBL, 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-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-7110-3P | 100.00 | 73.18 | 2486 |
| HSA-MIR-4283 | 100.00 | 66.42 | 2097 |
| HSA-MIR-450A-1-3P | 100.00 | 69.33 | 1837 |
| HSA-MIR-6873-3P | 100.00 | 71.42 | 2626 |
| HSA-MIR-5193 | 100.00 | 67.26 | 1744 |
| HSA-MIR-1229-3P | 99.97 | 66.49 | 906 |
| HSA-MIR-607 | 99.97 | 73.62 | 5593 |
| HSA-MIR-551B-5P | 99.96 | 71.28 | 3493 |
| HSA-MIR-6778-3P | 99.96 | 67.29 | 2693 |
| HSA-MIR-2110 | 99.96 | 66.68 | 1930 |
| HSA-MIR-9983-3P | 99.94 | 71.48 | 3631 |
| HSA-MIR-145-5P | 99.92 | 71.13 | 1836 |
| HSA-MIR-5195-3P | 99.92 | 70.92 | 1877 |
| HSA-MIR-6768-5P | 99.92 | 67.36 | 1942 |
| HSA-MIR-6783-3P | 99.89 | 67.92 | 2059 |
| HSA-MIR-548AZ-5P | 99.83 | 69.94 | 3230 |
| HSA-MIR-548T-5P | 99.83 | 69.91 | 3220 |
| HSA-MIR-4668-5P | 99.79 | 70.58 | 3782 |
| HSA-MIR-3934-3P | 99.76 | 65.51 | 1351 |
| HSA-MIR-4699-3P | 99.71 | 70.15 | 3142 |
| HSA-MIR-4729 | 99.69 | 72.18 | 4233 |
| HSA-MIR-17-3P | 99.55 | 66.77 | 1311 |
| HSA-MIR-3609 | 99.52 | 69.89 | 2587 |
| HSA-MIR-548AH-5P | 99.52 | 69.73 | 2626 |
| HSA-MIR-7159-3P | 99.51 | 70.17 | 1920 |
| HSA-MIR-4489 | 99.50 | 65.56 | 785 |
| HSA-MIR-6513-5P | 99.43 | 67.81 | 1071 |
| HSA-MIR-548AV-3P | 99.43 | 68.50 | 1721 |
| HSA-MIR-4316 | 99.37 | 65.75 | 1360 |
Literature-anchored findings (GeneRIF, showing 2)
- By comparing the enzyme kinetics and chemical inhibition properties between the recombinant protein and tissue preparations, CMBL was shown to be the primary olmesartan medoxomil bioactivating enzyme in the liver and intestine. (PMID:20177059)
- p53-responsive CMBL reprograms glucose metabolism and suppresses cancer development by destabilizing phosphofructokinase PFKP. (PMID:37967006)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | cmbl | ENSDARG00000073786 |
| mus_musculus | Cmbl | ENSMUSG00000022235 |
| rattus_norvegicus | Cmbl | ENSRNOG00000011260 |
Protein
Protein identifiers
Carboxymethylenebutenolidase homolog — Q96DG6 (reviewed: Q96DG6)
All UniProt accessions (1): Q96DG6
UniProt curated annotations — full annotation on UniProt →
Function. Cysteine hydrolase whose endogenous substrates and physiological function are unknown. Catalyzes the hydrolytic activation of several ester-based prodrugs, by cleaving the dioxolone ring to yield their respective active metabolites, diacetyl and CO2. Can thus convert the prodrugs Olmesartan medoxomil and Azilsartan medoxomil into their active metabolites (Olmesartan and Azilsartan), two angiotensin receptor blockers. Is also able to activate beta-lactam antibiotics Faropenem medoxomil and Lenampicillin.
Subcellular location. Cytoplasm. Cytosol.
Tissue specificity. Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level).
Activity regulation. Strongly inhibited by p-chloromercuribenzoate (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP). Not inhibited by DFP, PMSF, eserine or EDTA.
Similarity. Belongs to the dienelactone hydrolase family.
RefSeq proteins (1): NP_620164* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR002925 | Dienelactn_hydro | Domain |
| IPR029058 | AB_hydrolase_fold | Homologous_superfamily |
| IPR042946 | CMBL | Family |
Pfam: PF01738
Enzyme classification (BRENDA):
- EC 3.1.1.45 — carboxymethylenebutenolidase (BRENDA: 19 organisms, 75 substrates, 31 inhibitors, 42 Km, 41 kcat entries)
Substrate kinetics (BRENDA)
16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| 4-NITROPHENYL ACETATE | 0.012–0.014 | 6 |
| TRANS-4-CARBOXYMETHYLENEBUT-2-EN-4-OLIDE | 0.015–9.9 | 6 |
| CIS-4-CARBOXYMETHYLENEBUT-2-EN-4-OLIDE | 0.0281–0.59 | 5 |
| OLMESARTAN MEDOXOMIL | 0.16–0.48 | 5 |
| ALPHA-NAPHTHYL ACETATE | 0.02–0.074 | 4 |
| P-NITROPHENYL ACETATE | 0.007–0.021 | 4 |
| TRANS-DIENELACTONE | 0.1017–0.55 | 3 |
| 4-FLUOROMUCONOLACTONE | 1.2 | 1 |
| CIS-4-CARBOXYMETHYLENEBUT-2-CHLORO-2-EN-4-OLIDE | 0.0022 | 1 |
| CIS-4-CARBOXYMETHYLENEBUT-2-METHYL-2-EN-4-OLIDE | 0.31 | 1 |
| FAROPENEM MEDOXOMIL | 0.28 | 1 |
| LENAMPICILLIN | 0.063 | 1 |
| PROTOANEMONIN | 0.415 | 1 |
| 4-CARBOXYMETHYLENEBUT-2-EN-4-OLIDE | — | 0 |
| E-DIENELACTONE | — | 0 |
UniProt features (13 total): active site 3, modified residue 3, mutagenesis site 2, sequence conflict 2, initiator methionine 1, chain 1, sequence variant 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q96DG6-F1 | 91.92 | 0.83 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (3): 132 (nucleophile); 179; 212
Post-translational modifications (3): 2, 36, 223
Mutagenesis-validated functional residues (2):
| Position | Phenotype |
|---|---|
| 132 | 70% inhibition of enzymatic activity. |
| 132 | 97% inhibition of enzymatic activity. |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-211945 | Phase I - Functionalization of compounds |
MSigDB gene sets: 109 (showing top):
REACTOME_BIOLOGICAL_OXIDATIONS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, TSENG_IRS1_TARGETS_DN, SANSOM_APC_TARGETS_DN, BURTON_ADIPOGENESIS_6, CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP, CHICAS_RB1_TARGETS_CONFLUENT, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_17, KATSANOU_ELAVL1_TARGETS_UP, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D
GO Biological Process (1): xenobiotic metabolic process (GO:0006805)
GO Molecular Function (1): hydrolase activity (GO:0016787)
GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| Biological oxidations | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 2 |
| metabolic process | 1 |
| cellular response to xenobiotic stimulus | 1 |
| catalytic activity | 1 |
| cytoplasm | 1 |
| extracellular vesicle | 1 |
| intracellular anatomical structure | 1 |
Protein interactions and networks
STRING
1466 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| CMBL | ATPSCKMT | Q6P4H8 | 883 |
| CMBL | BTC | P35070 | 640 |
| CMBL | AREG | P15514 | 632 |
| CMBL | EREG | O14944 | 548 |
| CMBL | LHCGR | P22888 | 544 |
| CMBL | KRT14 | P02533 | 495 |
| CMBL | ZNF575 | Q86XF7 | 492 |
| CMBL | ROPN1L | Q96C74 | 476 |
| CMBL | AGTR1 | P30556 | 466 |
| CMBL | PRELID3B | Q9Y3B1 | 443 |
| CMBL | TK2 | O00142 | 425 |
| CMBL | BLOC1S6 | Q9UL45 | 414 |
| CMBL | IDH2 | P48735 | 408 |
| CMBL | ZNF114 | Q8NC26 | 402 |
| CMBL | SLC16A14 | Q7RTX9 | 401 |
IntAct
44 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| RCAN1 | PPP3CB | psi-mi:“MI:0914”(association) | 0.660 |
| steC | SCD | psi-mi:“MI:0914”(association) | 0.460 |
| CMBL | SMARCA2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| ECE1 | CMBL | psi-mi:“MI:0915”(physical association) | 0.370 |
| SMS | BAP1 | psi-mi:“MI:0914”(association) | 0.350 |
| SAP30 | BRMS1 | psi-mi:“MI:0914”(association) | 0.350 |
| Crocc | CLASP2 | psi-mi:“MI:0914”(association) | 0.350 |
| KIF20B | ACSL3 | psi-mi:“MI:0914”(association) | 0.350 |
| SNCA | SRRM1 | psi-mi:“MI:0914”(association) | 0.350 |
| Chmp6 | NSF | psi-mi:“MI:0914”(association) | 0.350 |
| ECH1 | A2ML1 | psi-mi:“MI:0914”(association) | 0.350 |
| CTCF | ZRANB2 | psi-mi:“MI:0914”(association) | 0.350 |
| CMBL | H2BC11 | psi-mi:“MI:0914”(association) | 0.350 |
| TRIM24 | DDTL | psi-mi:“MI:0914”(association) | 0.350 |
| TSPYL4 | CMBL | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF514 | SRSF10 | psi-mi:“MI:0914”(association) | 0.350 |
| P | psi-mi:“MI:0914”(association) | 0.350 | |
| M | psi-mi:“MI:0914”(association) | 0.350 | |
| H2AX | ANXA6 | psi-mi:“MI:0914”(association) | 0.350 |
| CMBL | TRAPPC13 | psi-mi:“MI:0914”(association) | 0.350 |
| SYNCRIP | psi-mi:“MI:0914”(association) | 0.350 | |
| TUB4q | psi-mi:“MI:0914”(association) | 0.350 | |
| FAM111A | DFFA | psi-mi:“MI:0914”(association) | 0.350 |
| FAM20B | PLEKHG3 | psi-mi:“MI:0914”(association) | 0.350 |
| GPX8 | CMBL | psi-mi:“MI:0914”(association) | 0.350 |
| HBB | HNRNPH2 | psi-mi:“MI:0914”(association) | 0.350 |
| INPP5K | UBR5 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (92): CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS), CMBL (Affinity Capture-MS)
ESM2 similar proteins: A0A1P8AWH8, A2Y8B9, F1QR43, F4JG10, F4JVN6, F4KFT7, O18756, O22975, O23617, O80574, O80596, O80738, O94923, Q06402, Q0VC13, Q0WUI9, Q10MJ1, Q1PET6, Q3U1V6, Q43093, Q43847, Q5IH13, Q5IH14, Q5MAU8, Q5VS72, Q6DHV7, Q6YXW6, Q6ZHE5, Q80SY6, Q8L7N4, Q8LB01, Q8VYP9, Q8VZF3, Q8W4K1, Q8W519, Q94AH8, Q94AS5, Q94E75, Q96DG6, Q99683
Diamond homologs: O67802, P46209, Q7TP52, Q96DG6, Q5RBU3, Q5XH09, Q6P7K0, Q8R1G2
SIGNOR signaling
0 interactions.
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 60 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 |
|---|---|---|---|
| CHD1 and CHD2 subfamily | 5 | 12.7× | 3e-03 |
| mRNA Polyadenylation | 6 | 12.3× | 9e-04 |
| Processing of Capped Intron-Containing Pre-mRNA | 6 | 11.5× | 9e-04 |
| mRNA Splicing - Major Pathway | 7 | 8.9× | 9e-04 |
| Dengue Virus-Host Interactions | 8 | 8.5× | 9e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
62 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 2 |
| Likely pathogenic | 0 |
| Uncertain significance | 43 |
| Likely benign | 4 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (2)
| Variant ID | HGVS | Classification |
|---|---|---|
| 2685147 | GRCh37/hg19 5p15.31-15.1(chr5:9002950-15174932)x1 | Pathogenic |
| 563031 | GRCh37/hg19 5p15.32-14.3(chr5:5830053-19490899)x1 | Pathogenic |
SpliceAI
884 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 5:10282195:A:AC | donor_gain | 1.0000 |
| 5:10282195:ACGT:A | donor_gain | 1.0000 |
| 5:10282196:C:CC | donor_gain | 1.0000 |
| 5:10282196:CGTC:C | donor_gain | 1.0000 |
| 5:10282198:T:TA | donor_gain | 1.0000 |
| 5:10282286:TGC:T | acceptor_gain | 1.0000 |
| 5:10282287:GC:G | acceptor_gain | 1.0000 |
| 5:10282288:CC:C | acceptor_gain | 1.0000 |
| 5:10282289:C:CC | acceptor_gain | 1.0000 |
| 5:10282289:CTGAA:C | acceptor_loss | 1.0000 |
| 5:10282290:T:A | acceptor_loss | 1.0000 |
| 5:10288525:TGGTT:T | acceptor_gain | 1.0000 |
| 5:10290546:A:AC | donor_gain | 1.0000 |
| 5:10290547:C:CC | donor_gain | 1.0000 |
| 5:10290559:T:A | donor_gain | 1.0000 |
| 5:10290782:C:CC | acceptor_gain | 1.0000 |
| 5:10282195:ACGTC:A | donor_gain | 0.9900 |
| 5:10282196:CGT:C | donor_gain | 0.9900 |
| 5:10282196:CGTCC:C | donor_gain | 0.9900 |
| 5:10282284:AATGC:A | acceptor_gain | 0.9900 |
| 5:10282285:ATGC:A | acceptor_gain | 0.9900 |
| 5:10288415:AACTC:A | donor_loss | 0.9900 |
| 5:10288417:CTC:C | donor_loss | 0.9900 |
| 5:10288418:TCA:T | donor_loss | 0.9900 |
| 5:10288419:C:CG | donor_loss | 0.9900 |
| 5:10288420:A:AT | donor_loss | 0.9900 |
| 5:10288526:GGTT:G | acceptor_gain | 0.9900 |
| 5:10288528:TT:T | acceptor_gain | 0.9900 |
| 5:10288530:C:CC | acceptor_gain | 0.9900 |
| 5:10290537:TTTA:T | donor_gain | 0.9900 |
AlphaMissense
1623 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 5:10280549:G:C | F214L | 0.997 |
| 5:10280549:G:T | F214L | 0.997 |
| 5:10280551:A:G | F214L | 0.997 |
| 5:10290614:T:A | D50V | 0.993 |
| 5:10280570:A:C | F207L | 0.991 |
| 5:10280570:A:T | F207L | 0.991 |
| 5:10280572:A:G | F207L | 0.991 |
| 5:10286427:G:C | F131L | 0.989 |
| 5:10286427:G:T | F131L | 0.989 |
| 5:10286429:A:G | F131L | 0.989 |
| 5:10290614:T:G | D50A | 0.986 |
| 5:10290615:C:G | D50H | 0.984 |
| 5:10290623:A:T | V47D | 0.981 |
| 5:10290603:A:G | W54R | 0.980 |
| 5:10290603:A:T | W54R | 0.980 |
| 5:10286428:A:G | F131S | 0.977 |
| 5:10286431:C:T | G130E | 0.977 |
| 5:10282220:C:G | D179H | 0.976 |
| 5:10286419:C:A | G134V | 0.976 |
| 5:10286423:A:G | W133R | 0.976 |
| 5:10286423:A:T | W133R | 0.976 |
| 5:10286424:G:C | C132W | 0.975 |
| 5:10290607:A:C | F52L | 0.975 |
| 5:10290607:A:T | F52L | 0.975 |
| 5:10290609:A:G | F52L | 0.975 |
| 5:10280555:A:C | H212Q | 0.974 |
| 5:10280555:A:T | H212Q | 0.974 |
| 5:10286426:A:G | C132R | 0.974 |
| 5:10280473:A:G | W240R | 0.973 |
| 5:10280473:A:T | W240R | 0.973 |
dbSNP variants (sampled 300 via entrez): RS1000141452 (5:10297772 G>A), RS1000246047 (5:10292018 A>G), RS1000385478 (5:10296421 C>T), RS1000404757 (5:10281837 C>A,T), RS1000417614 (5:10296159 A>T), RS1000441777 (5:10303559 G>A,T), RS1000590121 (5:10303200 T>G), RS1000630570 (5:10281985 C>T), RS1000776413 (5:10301947 G>A,C), RS1000841407 (5:10304055 C>T), RS1000872713 (5:10303706 T>C), RS1000920222 (5:10279735 T>C), RS1001327409 (5:10304767 A>G,T), RS1001510966 (5:10291515 G>A), RS1001549687 (5:10296274 G>A)
Disease associations
OMIM: gene MIM:613379 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
1 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST009391_720 | Metabolite levels | 5.000000e-06 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0010532 | salicylurate measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL6066502 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 7.28 | Kd | 52.35 | nM | CHEMBL5653589 |
| 7.25 | ED50 | 56.09 | nM | CHEMBL5653589 |
| 6.20 | Kd | 626.6 | nM | CHEMBL3752910 |
| 6.17 | ED50 | 671.4 | nM | CHEMBL3752910 |
PubChem BioAssay actives
2 with measured affinity, of 4 total; 2 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 |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148093: Binding affinity to human CMBL incubated for 45 mins by Kinobead based pull down assay | kd | 0.0524 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148093: Binding affinity to human CMBL incubated for 45 mins by Kinobead based pull down assay | kd | 0.6266 | uM |
CTD chemical–gene interactions
60 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | affects methylation, increases expression, increases methylation | 6 |
| Cisplatin | affects expression, affects cotreatment, increases expression | 4 |
| Aflatoxin B1 | affects expression, decreases expression, increases expression | 4 |
| Cyclosporine | affects expression, decreases expression | 3 |
| bisphenol A | decreases expression, increases expression | 2 |
| Acetaminophen | decreases expression, increases expression | 2 |
| Arsenic | affects methylation, increases abundance, increases expression | 2 |
| Estradiol | affects cotreatment, increases expression, decreases expression | 2 |
| Formaldehyde | decreases expression, increases expression | 2 |
| Testosterone | decreases expression, increases expression | 2 |
| Valproic Acid | affects expression, decreases expression | 2 |
| Cadmium Chloride | increases expression | 2 |
| bisphenol F | increases expression | 1 |
| bufotalin | decreases expression | 1 |
| chloroacetaldehyde | increases expression | 1 |
| lead acetate | affects cotreatment, increases expression | 1 |
| sodium arsenate | increases abundance, increases expression | 1 |
| zinc protoporphyrin | affects cotreatment, increases expression | 1 |
| sodium arsenite | decreases expression | 1 |
| butyraldehyde | decreases expression | 1 |
| aflatoxin B2 | decreases methylation | 1 |
| nickel sulfate | increases expression | 1 |
| beta-methylcholine | affects expression | 1 |
| pentanal | decreases expression | 1 |
| adefovir dipivoxil | increases expression | 1 |
| K 7174 | decreases expression | 1 |
| nutlin 3 | increases secretion, affects cotreatment | 1 |
| bisphenol B | increases expression | 1 |
| abrine | decreases expression | 1 |
| bisphenol S | increases expression | 1 |
ChEMBL screening assays
1 unique, capped per target: 1 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5651135 | Binding | Binding affinity to human CMBL incubated for 45 mins by Kinobead based pull down assay | NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem |
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.