TMEM33
gene geneOn this page
Also known as FLJ10525Pom33
Summary
TMEM33 (transmembrane protein 33, HGNC:25541) is a protein-coding gene on chromosome 4p13, encoding Transmembrane protein 33 (P57088). Acts as a regulator of the tubular endoplasmic reticulum (ER) network by modulating intracellular calcium homeostasis.
Involved in positive regulation of endoplasmic reticulum unfolded protein response; regulation of endoplasmic reticulum tubular network organization; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane; melanosome; and nuclear envelope.
Source: NCBI Gene 55161 — RefSeq curated summary.
At a glance
- GWAS associations: 3
- Clinical variants (ClinVar): 48 total
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_018126
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:25541 |
| Approved symbol | TMEM33 |
| Name | transmembrane protein 33 |
| Location | 4p13 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | FLJ10525, Pom33 |
| Ensembl gene | ENSG00000109133 |
| Ensembl biotype | protein_coding |
| OMIM | 618515 |
| Entrez | 55161 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron
ENST00000264452, ENST00000504986, ENST00000506794, ENST00000508448, ENST00000510383, ENST00000513558, ENST00000513702, ENST00000883748, ENST00000883749, ENST00000883750, ENST00000883751, ENST00000927658, ENST00000927659
RefSeq mRNA: 1 — MANE Select: NM_018126
NM_018126
CCDS: CCDS3464
Canonical transcript exons
ENST00000504986 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000712704 | 41939196 | 41939383 |
| ENSE00002055098 | 41935429 | 41935529 |
| ENSE00002083003 | 41954070 | 41960803 |
| ENSE00003529454 | 41949302 | 41949385 |
| ENSE00003546209 | 41944793 | 41944926 |
| ENSE00003554291 | 41943747 | 41943814 |
| ENSE00003648204 | 41938602 | 41938696 |
Expression profiles
Bgee: expression breadth ubiquitous, 287 present calls, max score 95.70.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.9983 / max 307.8646, expressed in 1827 samples.
FANTOM5 promoters (6 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 47500 | 61.8881 | 1827 |
| 47502 | 3.6018 | 1434 |
| 47501 | 1.5171 | 971 |
| 47504 | 0.4596 | 199 |
| 47503 | 0.3513 | 152 |
| 203157 | 0.1804 | 54 |
Top tissues by expression
294 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| adrenal tissue | UBERON:0018303 | 95.70 | gold quality |
| buccal mucosa cell | CL:0002336 | 95.58 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 94.65 | gold quality |
| retina | UBERON:0000966 | 94.63 | gold quality |
| islet of Langerhans | UBERON:0000006 | 93.63 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 93.53 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 93.44 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 93.01 | gold quality |
| medial globus pallidus | UBERON:0002477 | 93.00 | gold quality |
| upper leg skin | UBERON:0004262 | 92.96 | gold quality |
| colonic mucosa | UBERON:0000317 | 92.88 | gold quality |
| corpus epididymis | UBERON:0004359 | 92.71 | gold quality |
| gingiva | UBERON:0001828 | 92.17 | gold quality |
| gingival epithelium | UBERON:0001949 | 92.09 | gold quality |
| caput epididymis | UBERON:0004358 | 92.09 | gold quality |
| globus pallidus | UBERON:0001875 | 91.95 | gold quality |
| squamous epithelium | UBERON:0006914 | 91.93 | gold quality |
| mammalian vulva | UBERON:0000997 | 91.82 | gold quality |
| monocyte | CL:0000576 | 91.72 | gold quality |
| mononuclear cell | CL:0000842 | 91.49 | gold quality |
| leukocyte | CL:0000738 | 91.36 | gold quality |
| duodenum | UBERON:0002114 | 90.88 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 90.85 | gold quality |
| blood | UBERON:0000178 | 90.70 | gold quality |
| tibia | UBERON:0000979 | 90.69 | gold quality |
| tendon | UBERON:0000043 | 90.66 | gold quality |
| placenta | UBERON:0001987 | 90.32 | gold quality |
| corpus callosum | UBERON:0002336 | 90.26 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 90.22 | gold quality |
| postcentral gyrus | UBERON:0002581 | 90.17 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 10.67 |
| E-MTAB-6524 | no | 143.40 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): TP53
miRNA regulators (miRDB)
339 targeting TMEM33, 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-1252-5P | 100.00 | 69.80 | 2774 |
| HSA-MIR-4795-3P | 100.00 | 74.62 | 4024 |
| HSA-MIR-3924 | 100.00 | 72.09 | 2394 |
| HSA-MIR-126-5P | 100.00 | 72.71 | 3180 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-6833-3P | 100.00 | 70.63 | 3197 |
| HSA-MIR-29A-3P | 100.00 | 73.11 | 1835 |
| HSA-MIR-29B-3P | 100.00 | 73.18 | 1833 |
| HSA-MIR-29C-3P | 100.00 | 73.15 | 1833 |
| HSA-MIR-4768-5P | 100.00 | 69.49 | 2861 |
| HSA-MIR-4262 | 100.00 | 73.26 | 3931 |
| HSA-MIR-200B-3P | 100.00 | 73.31 | 2693 |
| HSA-MIR-200C-3P | 100.00 | 73.35 | 2685 |
| HSA-MIR-429 | 100.00 | 73.44 | 2698 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-1277-5P | 100.00 | 73.95 | 5056 |
| HSA-MIR-4668-3P | 100.00 | 68.74 | 2635 |
| HSA-MIR-9-5P | 100.00 | 72.28 | 2361 |
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-5692B | 100.00 | 71.32 | 2622 |
| HSA-MIR-5692C | 100.00 | 71.32 | 2622 |
| HSA-MIR-12118 | 100.00 | 65.88 | 1270 |
| HSA-MIR-513A-5P | 100.00 | 69.77 | 2465 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-196A-1-3P | 99.99 | 72.15 | 2772 |
Literature-anchored findings (GeneRIF, showing 2)
- TMEM33 is a novel regulator of the PERK-eIE2alpha-ATF4 and IRE1-XBP1 axes of the UPR signaling. (PMID:26268696)
- PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. (PMID:34487377)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | tmem33 | ENSDARG00000041332 |
| mus_musculus | Tmem33 | ENSMUSG00000037720 |
| rattus_norvegicus | Tmem33 | ENSRNOG00000002254 |
| drosophila_melanogaster | Kr-h2 | FBGN0266449 |
| caenorhabditis_elegans | WBGENE00012555 |
Protein
Protein identifiers
Transmembrane protein 33 — P57088 (reviewed: P57088)
Alternative names: Protein DB83, SHINC-3
All UniProt accessions (5): P57088, D6RAA6, D6RBY2, H0Y8N0, J3KN43
UniProt curated annotations — full annotation on UniProt →
Function. Acts as a regulator of the tubular endoplasmic reticulum (ER) network by modulating intracellular calcium homeostasis. Mechanistically, stimulates PKD2 calcium-dependent activity. Suppresses the RTN3/4-induced formation of the ER tubules. Positively regulates PERK-mediated and IRE1-mediated unfolded protein response signaling. Plays an essential role in VEGF-mediated release of Ca(2+) from ER stores during angiogenesis. Also plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26. Participates in lipid metabolism by acting as a downstream effector of the pyruvate kinase/PKM. Forms a complex with RNF5 to facilitate polyubiquitination and subsequent degradation of SCAP on the ER membrane.
Subunit / interactions. Interacts with EIF2AK3. Interacts with ARL6IP1, isoform RTN1-A of RTN1, isoform RTN2-B of RTN2, isoform 3 of RTN3 and isoform 3 of RTN4. Interacts with RNF5. Interacts with RNF26. Interacts with PKD2.
Subcellular location. Endoplasmic reticulum membrane. Melanosome. Nucleus envelope.
Tissue specificity. Prostate cancer and several cancer cell lines (at protein level). Widely expressed. Expressed at higher levels in endocrine-resistant breast cancer cells as compared to endocrine-sensitive breast cancer cells. Expressed at higher levels in early recurrence breast cancer tissues as compared to non-recurrent breast tumors.
Induction. By endoplasmic reticulum (ER) stress.
Similarity. Belongs to the PER33/POM33 family.
RefSeq proteins (1): NP_060596* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR005344 | TMEM33/Pom33 | Family |
| IPR051645 | PER33/POM33_regulator | Family |
Pfam: PF03661
UniProt features (11 total): topological domain 4, transmembrane region 3, initiator methionine 1, chain 1, sequence conflict 1, modified residue 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P57088-F1 | 88.85 | 0.65 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (1): 2
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 234 (showing top):
ELVIDGE_HYPOXIA_DN, HORIUCHI_WTAP_TARGETS_DN, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, AACYNNNNTTCCS_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, ATGTTAA_MIR302C, GOBP_REGULATION_OF_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_ER_NUCLEUS_SIGNALING_PATHWAY, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GARY_CD5_TARGETS_DN, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION
GO Biological Process (8): response to endoplasmic reticulum stress (GO:0034976), innate immune response (GO:0045087), membrane organization (GO:0061024), endoplasmic reticulum tubular network organization (GO:0071786), regulation of endoplasmic reticulum tubular network organization (GO:1903371), positive regulation of IRE1-mediated unfolded protein response (GO:1903896), positive regulation of PERK-mediated unfolded protein response (GO:1903899), immune system process (GO:0002376)
GO Molecular Function (1): protein binding (GO:0005515)
GO Cellular Component (6): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), melanosome (GO:0042470), nucleus (GO:0005634), membrane (GO:0016020)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| positive regulation of endoplasmic reticulum unfolded protein response | 2 |
| endomembrane system | 2 |
| intracellular membrane-bounded organelle | 2 |
| cellular response to stress | 1 |
| immune response | 1 |
| defense response to symbiont | 1 |
| cellular component organization | 1 |
| endoplasmic reticulum organization | 1 |
| regulation of organelle organization | 1 |
| endoplasmic reticulum tubular network organization | 1 |
| IRE1-mediated unfolded protein response | 1 |
| regulation of IRE1-mediated unfolded protein response | 1 |
| PERK-mediated unfolded protein response | 1 |
| regulation of PERK-mediated unfolded protein response | 1 |
| biological_process | 1 |
| binding | 1 |
| nucleus | 1 |
| organelle envelope | 1 |
| cytoplasm | 1 |
| organelle membrane | 1 |
| nuclear outer membrane-endoplasmic reticulum membrane network | 1 |
| endoplasmic reticulum subcompartment | 1 |
| pigment granule | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
890 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| TMEM33 | RTN1 | Q16799 | 802 |
| TMEM33 | ENDOD1 | O94919 | 706 |
| TMEM33 | RNF26 | Q9BY78 | 677 |
| TMEM33 | TMEM43 | Q9BTV4 | 645 |
| TMEM33 | NUP210 | Q8TEM1 | 640 |
| TMEM33 | REEP5 | Q00765 | 616 |
| TMEM33 | SLC30A9 | Q6PML9 | 607 |
| TMEM33 | NUP133 | Q8WUM0 | 606 |
| TMEM33 | AHCTF1 | Q8WYP5 | 563 |
| TMEM33 | SEC13 | P55735 | 558 |
| TMEM33 | TMED1 | Q13445 | 529 |
| TMEM33 | NUP85 | Q9BW27 | 528 |
| TMEM33 | NDC1 | Q9BTX1 | 526 |
| TMEM33 | CFAP299 | Q6V702 | 504 |
| TMEM33 | PKD2 | Q13563 | 492 |
IntAct
192 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| MAP3K14 | CHUK | psi-mi:“MI:0914”(association) | 0.950 |
| EMC3 | EMC8 | psi-mi:“MI:0914”(association) | 0.730 |
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| BRAF | KRAS | psi-mi:“MI:0914”(association) | 0.680 |
| TMEM33 | MTNR1A | psi-mi:“MI:0915”(physical association) | 0.660 |
| MAPK7 | PFDN6 | psi-mi:“MI:0914”(association) | 0.640 |
| RAF1 | CALU | psi-mi:“MI:0914”(association) | 0.640 |
| DDX3X | psi-mi:“MI:0914”(association) | 0.630 | |
| TMEM33 | psi-mi:“MI:0915”(physical association) | 0.560 | |
| MTNR1A | PGRMC1 | psi-mi:“MI:0914”(association) | 0.530 |
| XPO1 | psi-mi:“MI:0914”(association) | 0.530 | |
| SLC30A2 | ESYT2 | psi-mi:“MI:0914”(association) | 0.530 |
| ERBB2 | NDUFA4 | psi-mi:“MI:0914”(association) | 0.530 |
| CFTR | PLEKHG3 | psi-mi:“MI:0914”(association) | 0.480 |
BioGRID (275): ABCC1 (Co-fractionation), TMEM33 (Affinity Capture-MS), TMEM33 (Proximity Label-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Reconstituted Complex), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TMEM33 (Affinity Capture-MS)
ESM2 similar proteins: A0MT11, A4FV75, A4QNE0, A5A6S6, A6H7C2, A6ZIQ8, O35841, O80845, P56589, P57088, Q10SM7, Q148K5, Q15005, Q28250, Q2KII7, Q2TBU2, Q3TMP8, Q3ZBE6, Q4R512, Q4R5B4, Q5BJI9, Q5M8Y1, Q5R644, Q5RAY6, Q5RF53, Q5U4F4, Q5VRJ8, Q5XIK2, Q5ZKG8, Q60HE1, Q6GLK9, Q6GQ39, Q6NRL4, Q84JW1, Q86UB9, Q91XC9, Q9BZZ5, Q9CR67, Q9CYN2, Q9CYV5
Diamond homologs: P57088, Q9CR67, Q9V447, Q9XWV0, Q9Z142
SIGNOR signaling
0 interactions.
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 209 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 |
|---|---|---|---|
| CD209 (DC-SIGN) signaling | 5 | 17.5× | 6e-04 |
| RAF activation | 7 | 15.9× | 2e-04 |
| Signaling by high-kinase activity BRAF mutants | 7 | 15.0× | 2e-04 |
| MAP2K and MAPK activation | 7 | 13.5× | 2e-04 |
| Negative regulation of MAPK pathway | 7 | 12.6× | 2e-04 |
| Signaling by moderate kinase activity BRAF mutants | 7 | 12.0× | 2e-04 |
| Paradoxical activation of RAF signaling by kinase inactive BRAF | 7 | 12.0× | 2e-04 |
| Signaling downstream of RAS mutants | 7 | 12.0× | 2e-04 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| regulation of intracellular pH | 8 | 26.6× | 6e-07 |
| bicarbonate transport | 6 | 26.6× | 5e-05 |
| MAPK cascade | 10 | 8.5× | 2e-04 |
| transmembrane transport | 9 | 8.4× | 5e-04 |
| response to ethanol | 8 | 6.5× | 9e-03 |
| cell migration | 12 | 4.1× | 1e-02 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
48 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 33 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1156 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 4:41935915:A:T | donor_gain | 1.0000 |
| 4:41935963:G:T | donor_gain | 1.0000 |
| 4:41938600:A:AG | acceptor_gain | 1.0000 |
| 4:41938601:G:GG | acceptor_gain | 1.0000 |
| 4:41939290:T:G | donor_gain | 1.0000 |
| 4:41939378:TTAC:T | donor_gain | 1.0000 |
| 4:41943746:GT:G | acceptor_gain | 1.0000 |
| 4:41943746:GTGA:G | acceptor_gain | 1.0000 |
| 4:41944789:TTA:T | acceptor_loss | 1.0000 |
| 4:41944790:TA:T | acceptor_loss | 1.0000 |
| 4:41944790:TAGG:T | acceptor_gain | 1.0000 |
| 4:41944791:A:AC | acceptor_loss | 1.0000 |
| 4:41944791:A:AG | acceptor_gain | 1.0000 |
| 4:41944792:G:A | acceptor_loss | 1.0000 |
| 4:41944792:G:GG | acceptor_gain | 1.0000 |
| 4:41944792:GGC:G | acceptor_gain | 1.0000 |
| 4:41944792:GGCA:G | acceptor_gain | 1.0000 |
| 4:41944792:GGCAA:G | acceptor_gain | 1.0000 |
| 4:41944924:TAGG:T | donor_loss | 1.0000 |
| 4:41944925:AGGT:A | donor_loss | 1.0000 |
| 4:41944926:GGTA:G | donor_loss | 1.0000 |
| 4:41944927:G:GA | donor_loss | 1.0000 |
| 4:41944927:G:GG | donor_gain | 1.0000 |
| 4:41944928:T:G | donor_loss | 1.0000 |
| 4:41949300:A:AG | acceptor_gain | 1.0000 |
| 4:41949300:AGT:A | acceptor_gain | 1.0000 |
| 4:41949301:G:GT | acceptor_gain | 1.0000 |
| 4:41949301:GT:G | acceptor_gain | 1.0000 |
| 4:41949301:GTG:G | acceptor_gain | 1.0000 |
| 4:41935450:C:CA | acceptor_gain | 0.9900 |
AlphaMissense
1608 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 4:41939251:A:C | S66R | 1.000 |
| 4:41939253:T:A | S66R | 1.000 |
| 4:41939253:T:G | S66R | 1.000 |
| 4:41939255:C:A | A67D | 1.000 |
| 4:41939264:T:C | L70P | 1.000 |
| 4:41939326:G:C | D91H | 1.000 |
| 4:41939326:G:T | D91Y | 1.000 |
| 4:41939327:A:C | D91A | 1.000 |
| 4:41939327:A:G | D91G | 1.000 |
| 4:41939327:A:T | D91V | 1.000 |
| 4:41939342:T:C | L96P | 1.000 |
| 4:41943770:T:C | F118L | 1.000 |
| 4:41943772:C:A | F118L | 1.000 |
| 4:41943772:C:G | F118L | 1.000 |
| 4:41944878:C:A | A161D | 1.000 |
| 4:41944887:A:T | E164V | 1.000 |
| 4:41944890:T:A | I165K | 1.000 |
| 4:41949342:T:C | F191L | 1.000 |
| 4:41949343:T:C | F191S | 1.000 |
| 4:41949344:T:A | F191L | 1.000 |
| 4:41949344:T:G | F191L | 1.000 |
| 4:41949346:T:C | L192P | 1.000 |
| 4:41949364:C:T | S198F | 1.000 |
| 4:41949374:C:A | N201K | 1.000 |
| 4:41949374:C:G | N201K | 1.000 |
| 4:41938638:T:A | W28R | 0.999 |
| 4:41938638:T:C | W28R | 0.999 |
| 4:41939218:T:G | Y55D | 0.999 |
| 4:41939228:C:A | A58D | 0.999 |
| 4:41939231:T:C | L59S | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000045598 (4:41956890 A>C), RS1000112069 (4:41949069 A>G), RS1000135817 (4:41944557 G>A), RS1000177840 (4:41935776 A>G), RS1000225819 (4:41942284 A>G), RS1000383839 (4:41951006 A>G), RS1000674583 (4:41959676 A>C), RS1000783324 (4:41952661 G>A), RS1000818318 (4:41951204 A>AAATGTGT), RS1000835254 (4:41954731 G>A), RS1000863963 (4:41936114 G>A), RS1000886183 (4:41954459 A>G), RS1001066590 (4:41947969 A>G), RS1001382082 (4:41955819 G>A,T), RS1001435673 (4:41940801 CCTT>C)
Disease associations
OMIM: gene MIM:618515 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST005355_3 | Helping behaviour (self reported) | 5.000000e-07 |
| GCST005355_5 | Helping behaviour (self reported) | 3.000000e-06 |
| GCST006940_94 | Neurociticism | 4.000000e-08 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007660 | neuroticism measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5724606 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1232461 | MOLIBRESIB | 2 | 1,538 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.28 | Kd | 5.302 | nM | CHEMBL5653589 |
| 8.28 | ED50 | 5.302 | nM | CHEMBL5653589 |
| 6.44 | IC50 | 360 | nM | MOLIBRESIB |
| 5.31 | Kd | 4889 | nM | CHEMBL3752910 |
| 5.31 | ED50 | 4889 | nM | CHEMBL3752910 |
PubChem BioAssay actives
3 with measured affinity, of 10 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 |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149613: Binding affinity to human TMEM33 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0053 | uM |
| 2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide | 2178717: Inhibition of TMEM33 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis | ic50 | 0.3600 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2149613: Binding affinity to human TMEM33 incubated for 45 mins by Kinobead based pull down assay | kd | 4.8887 | uM |
CTD chemical–gene interactions
41 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | decreases expression | 3 |
| sodium arsenite | decreases expression, affects cotreatment, increases abundance, increases expression | 3 |
| Cadmium Chloride | increases abundance, increases expression, decreases expression | 3 |
| Valproic Acid | decreases expression, increases expression | 2 |
| Cyclosporine | increases expression | 2 |
| geldanamycin | increases expression | 1 |
| 2,4,6-tribromophenol | decreases expression | 1 |
| methylmercuric chloride | increases expression, decreases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| decabromobiphenyl ether | decreases expression | 1 |
| beta-lapachone | increases expression | 1 |
| tetrabromobisphenol A | decreases expression | 1 |
| zinc chromate | increases abundance, increases expression | 1 |
| manganese chloride | increases abundance, increases expression, affects cotreatment | 1 |
| chromium hexavalent ion | increases abundance, increases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| ICG 001 | increases expression | 1 |
| abrine | decreases expression | 1 |
| pentabrominated diphenyl ether 100 | decreases expression | 1 |
| hexabrominated diphenyl ether 153 | decreases expression | 1 |
| jinfukang | decreases expression | 1 |
| LDN 193189 | affects cotreatment, decreases expression | 1 |
| (+)-JQ1 compound | decreases expression | 1 |
| bisphenol AF | increases expression | 1 |
| Resveratrol | affects cotreatment, increases expression | 1 |
| Vorinostat | decreases expression | 1 |
| Arsenic | affects cotreatment, increases abundance, increases expression | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Cadmium | increases abundance, increases expression | 1 |
ChEMBL screening assays
7 unique, capped per target: 7 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5652655 | Binding | Binding affinity to human TMEM33 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.