MLN
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Summary
MLN (motilin, HGNC:7141) is a protein-coding gene on chromosome 6p21.31, encoding Promotilin (P12872). Plays an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle.
This gene encodes a small peptide hormone that is secreted by cells of the small intestine to regulate gastrointestinal contractions and motility. Proteolytic processing of the secreted protein produces the mature peptide and a byproduct referred to as motilin-associated peptide (MAP). Three transcript variants encoding different preproprotein isoforms but the same mature peptide have been found for this gene.
Source: NCBI Gene 4295 — RefSeq curated summary.
At a glance
- Clinical variants (ClinVar): 19 total
- Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.63 (unconstrained)
- MANE Select transcript:
NM_002418
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:7141 |
| Approved symbol | MLN |
| Name | motilin |
| Location | 6p21.31 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000096395 |
| Ensembl biotype | protein_coding |
| OMIM | 158270 |
| Entrez | 4295 |
Gene structure
Transcript identifiers
Ensembl transcripts: 6 — 6 protein_coding
MANE Select: ENST00000430124
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 1
ENST00000430124, ENST00000266003, ENST00000507738, ENST00000960632, ENST00001090880, ENST00001133652
RefSeq mRNA: 3 — MANE Select: NM_002418
NM_001040109, NM_001184698, NM_002418
CCDS: CCDS47412, CCDS4786, CCDS54993
Canonical transcript exons
ENST00000430124 — 5 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000738724 | 33799105 | 33799221 |
| ENSE00000849455 | 33795503 | 33795605 |
| ENSE00000849456 | 33801047 | 33801170 |
| ENSE00001675754 | 33794673 | 33794835 |
| ENSE00001817221 | 33803953 | 33804003 |
Expression profiles
Bgee: expression breadth ubiquitous, 116 present calls, max score 92.54.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2453 / max 128.0077, expressed in 19 samples.
Highest expression (Bgee): duodenum, jejunal mucosa, jejunum, cervix squamous epithelium, diaphragm.
Genetic regulation across tissues (GTEx eQTL / sQTL)
MLN is not an eGene in any GTEx v10 tissue: no tissue shows a variant significantly associated with its expression or splicing (q < 0.05).
FANTOM5 promoters
1 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 73192 | 0.2453 | 19 |
Top tissues by expression
showing 100 of 271 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| duodenum | UBERON:0002114 | 92.54 | gold quality |
| jejunal mucosa | UBERON:0000399 | 82.85 | gold quality |
| jejunum | UBERON:0002115 | 76.34 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 71.76 | gold quality |
| diaphragm | UBERON:0001103 | 71.09 | gold quality |
| endometrium epithelium | UBERON:0004811 | 71.06 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 70.58 | gold quality |
| frontal pole | UBERON:0002795 | 69.54 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 69.18 | gold quality |
| paraflocculus | UBERON:0005351 | 69.13 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 68.83 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 68.30 | gold quality |
| thymus | UBERON:0002370 | 68.17 | gold quality |
| oocyte | CL:0000023 | 67.87 | gold quality |
| olfactory bulb | UBERON:0002264 | 67.20 | gold quality |
| secondary oocyte | CL:0000655 | 67.12 | gold quality |
| cerebellar vermis | UBERON:0004720 | 66.52 | gold quality |
| cervix epithelium | UBERON:0004801 | 65.26 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 65.01 | gold quality |
| trachea | UBERON:0003126 | 64.73 | gold quality |
| orbitofrontal cortex | UBERON:0004167 | 64.35 | gold quality |
| type B pancreatic cell | CL:0000169 | 63.13 | gold quality |
| pancreatic ductal cell | CL:0002079 | 63.01 | silver quality |
| nipple | UBERON:0002030 | 62.69 | gold quality |
| dorsal plus ventral thalamus | UBERON:0001897 | 62.34 | gold quality |
| pericardium | UBERON:0002407 | 62.13 | gold quality |
| cardia of stomach | UBERON:0001162 | 62.10 | gold quality |
| dorsal root ganglion | UBERON:0000044 | 62.04 | gold quality |
| upper arm skin | UBERON:0004263 | 62.04 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 61.72 | gold quality |
| pylorus | UBERON:0001166 | 61.71 | gold quality |
| saphenous vein | UBERON:0007318 | 61.64 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 61.46 | gold quality |
| synovial joint | UBERON:0002217 | 61.43 | gold quality |
| ventral tegmental area | UBERON:0002691 | 61.37 | gold quality |
| tongue | UBERON:0001723 | 61.33 | gold quality |
| inferior vagus X ganglion | UBERON:0005363 | 61.32 | gold quality |
| subthalamic nucleus | UBERON:0001906 | 61.22 | gold quality |
| mucosa of urinary bladder | UBERON:0001259 | 61.16 | gold quality |
| tibialis anterior | UBERON:0001385 | 61.08 | silver quality |
| deltoid | UBERON:0001476 | 61.03 | gold quality |
| pons | UBERON:0000988 | 61.01 | gold quality |
| substantia nigra pars reticulata | UBERON:0001966 | 60.95 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 60.87 | gold quality |
| superior surface of tongue | UBERON:0007371 | 60.83 | gold quality |
| renal medulla | UBERON:0000362 | 60.78 | gold quality |
| body of tongue | UBERON:0011876 | 60.72 | gold quality |
| quadriceps femoris | UBERON:0001377 | 60.63 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 60.63 | gold quality |
| urethra | UBERON:0000057 | 60.62 | gold quality |
| medulla oblongata | UBERON:0001896 | 60.49 | gold quality |
| penis | UBERON:0000989 | 60.42 | gold quality |
| lateral nuclear group of thalamus | UBERON:0002736 | 60.41 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 60.35 | gold quality |
| vena cava | UBERON:0004087 | 60.24 | gold quality |
| substantia nigra pars compacta | UBERON:0001965 | 60.15 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 60.10 | gold quality |
| squamous epithelium | UBERON:0006914 | 60.08 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 59.79 | gold quality |
| superior vestibular nucleus | UBERON:0007227 | 59.71 | gold quality |
| ileal mucosa | UBERON:0000331 | 59.58 | silver quality |
| gingival epithelium | UBERON:0001949 | 59.53 | gold quality |
| decidua | UBERON:0002450 | 59.11 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 59.07 | gold quality |
| gluteal muscle | UBERON:0002000 | 59.02 | gold quality |
| triceps brachii | UBERON:0001509 | 58.91 | gold quality |
| vastus lateralis | UBERON:0001379 | 58.77 | gold quality |
| cartilage tissue | UBERON:0002418 | 58.52 | gold quality |
| gingiva | UBERON:0001828 | 58.51 | gold quality |
| epithelium of mammary gland | UBERON:0003244 | 58.41 | gold quality |
| amniotic fluid | UBERON:0000173 | 58.37 | gold quality |
| mammary duct | UBERON:0001765 | 57.83 | gold quality |
| oviduct epithelium | UBERON:0004804 | 57.81 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 57.57 | silver quality |
| epithelium of esophagus | UBERON:0001976 | 57.13 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 57.08 | gold quality |
| muscle tissue | UBERON:0002385 | 56.62 | gold quality |
| hair follicle | UBERON:0002073 | 56.16 | gold quality |
| parietal lobe | UBERON:0001872 | 55.85 | gold quality |
| biceps brachii | UBERON:0001507 | 55.69 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 55.53 | gold quality |
| inferior olivary complex | UBERON:0002127 | 55.49 | gold quality |
| buccal mucosa cell | CL:0002336 | 55.24 | gold quality |
| male germ cell | CL:0000015 | 54.99 | gold quality |
| mammalian vulva | UBERON:0000997 | 54.85 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 54.80 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 54.79 | gold quality |
| postcentral gyrus | UBERON:0002581 | 54.68 | gold quality |
| pleura | UBERON:0000977 | 54.51 | gold quality |
| myocardium | UBERON:0002349 | 54.22 | gold quality |
| sperm | CL:0000019 | 53.88 | gold quality |
| parietal pleura | UBERON:0002400 | 53.75 | gold quality |
| cranial nerve II | UBERON:0000941 | 53.68 | silver quality |
| small intestine | UBERON:0002108 | 53.68 | gold quality |
| colonic mucosa | UBERON:0000317 | 53.66 | gold quality |
| corpus epididymis | UBERON:0004359 | 53.49 | gold quality |
| oral cavity | UBERON:0000167 | 53.48 | gold quality |
| entorhinal cortex | UBERON:0002728 | 53.39 | gold quality |
| visceral pleura | UBERON:0002401 | 53.38 | gold quality |
| cauda epididymis | UBERON:0004360 | 52.10 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.98 |
HPA expression
RNA tissue specificity: Tissue enriched
showing 60 of 83 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Duodenum | tissue | 239.2 | high |
| Tongue | tissue | 137.2 | |
| Skeletal muscle | tissue | 117.4 | |
| Small intestine | tissue | 40.8 | high |
| Retina | tissue | 28.2 | |
| Cerebellum | tissue | 21.6 | |
| Pituitary gland | tissue | 7.7 | |
| Kidney | tissue | 7.5 | |
| Fallopian tube | tissue | 4.8 | |
| Pancreas | tissue | 2.6 | |
| Medulla oblongata | tissue | 2.3 | |
| Choroid plexus | tissue | 2.0 | |
| Putamen | tissue | 1.9 | |
| Thalamus | tissue | 1.9 | |
| Retrosplenial cortex | tissue | 1.9 | |
| Pons | tissue | 1.6 | |
| Hippocampus | tissue | 1.6 | |
| Basal ganglia | tissue | 1.5 | |
| Midbrain | tissue | 1.5 | |
| Substantia nigra | tissue | 1.5 | |
| Spinal cord | tissue | 1.5 | |
| Septum | tissue | 1.5 | |
| Locus coeruleus | tissue | 1.4 | |
| Olfactory bulb | tissue | 1.4 | |
| Locus coeruleus | tissue | 1.3 | |
| Nucleus accumbens | tissue | 1.3 | |
| Corpus callosum | tissue | 1.3 | |
| Prostate | tissue | 1.2 | |
| Entorhinal cortex | tissue | 1.2 | |
| Esophagus | tissue | 1.1 | |
| Postcentral gyrus | tissue | 1.1 | |
| Stomach 1 | tissue | 1.0 | |
| Hypothalamus | tissue | 0.9 | |
| Postcentral gyrus | tissue | 0.8 | |
| Duodenum | tissue | 0.8 | |
| Testis | tissue | 0.7 | |
| Lung | tissue | 0.7 | |
| Small intestine | tissue | 0.7 | |
| Gallbladder | tissue | 0.7 | |
| Nucleus accumbens | tissue | 0.6 | |
| Skin 1 | tissue | 0.6 | |
| Cerebral cortex | tissue | 0.6 | |
| Epididymis | tissue | 0.6 | |
| Ventral forebrain | tissue | 0.6 | |
| Retrosplenial and cingulate cortex | tissue | 0.6 | |
| Appendix | tissue | 0.5 | not detected |
| Cervix | tissue | 0.5 | |
| Endometrium 1 | tissue | 0.5 | |
| Spleen | tissue | 0.5 | |
| Hippocampal formation | tissue | 0.5 | |
| Occipital cortex | tissue | 0.5 | |
| Choroid plexus | tissue | 0.4 | |
| Hippocampus | tissue | 0.4 | not detected |
| Skin 1 | tissue | 0.3 | not detected |
| Lymph node | tissue | 0.3 | not detected |
| Testis | tissue | 0.3 | not detected |
| Thymus | tissue | 0.3 | |
| Retina | tissue | 0.2 | |
| Adrenal gland | tissue | 0.2 | not detected |
| Thymus | tissue | 0.2 |
Brain sub-regions (HPA Brain Atlas): detected in 367; highest nTPM — Cerebellar cortex (10.6), Flocculonodular lobe (9.6), Vermis (9.1), Reticular pontine nucleus, oral (3.2), Nucleus raphe obscurus (2.8).
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
Targeting MLN by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
3 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-1251-3P | 99.64 | 67.21 | 1408 |
| HSA-MIR-3978 | 99.24 | 68.39 | 2201 |
| HSA-MIR-6774-5P | 95.94 | 65.18 | 722 |
Functional genomics
gnomAD constraint: pLI 0.0185, LOEUF 1.63, missense Z -0.145 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000430124 — one region, missense o/e 0.85.
Literature-anchored findings (GeneRIF, showing 12)
- Plasma levels of motilin were studied in 16 untreated Celiac disease patients and in an age-matched control group of 18 healthy subjects by radioimmunoassay and by high-performance liquid chromatography (HPLC). (PMID:12732349)
- Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine. (PMID:17595255)
- The abnormal excretion of hormonal factors is closely related to gallstone formation (PMID:18234640)
- About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. (PMID:18609694)
- Ghrelin covaried with motilin in plasma in irritable bowel syndrome (IBS) but not in plasma from healthy subjects. This suggests the two peptides act together in IBS. (PMID:20338210)
- Motilin may directly influence adipocyte functions by stimulating energy storage. (PMID:21771971)
- Motilin stimulates growth hormone secretion and regulates interdigestive migrating contractions and fasting motor patterns in the gastrointestinal tract. [REVIEW] (PMID:22632857)
- motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients–{REVIEW} (PMID:26660537)
- Serum motilin levels and motilin gene polymorphisms in children with functional constipation. (PMID:27706119)
- Hemodialysis improves upper GI symptoms and gastric slow waves in CKD patients. An increase in ghrelin and a decrease in GLP-1 might be involved in the HD-induced improvement in gastric slow waves. (PMID:28566304)
- Physiological functions and potential clinical applications of motilin. (PMID:36436612)
- Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation. (PMID:36888769)
Cross-species orthologs
0 orthologs
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Canis lupus familiaris | P19863 | 95.5% | Diamond |
| Felis catus | Q9XSE2 | 95.5% | Diamond |
| Macaca mulatta | O18811 | 93.9% | Diamond |
| Ovis aries | O18845 | 92.2% | Diamond |
| Bos taurus | O62820 | 92.2% | Diamond |
| Equus caballus | O46617 | 80.9% | Diamond |
| Sus scrofa | P01307 | 78.1% | Diamond |
| Oryctolagus cuniculus | P27114 | 77.5% | Diamond |
| Cavia porcellus | Q99MP5 | 72.8% | Diamond |
| Gallus gallus | Q9PRP6 | 72.7% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| IP6K3 | protein-coding | 117283 |
| LEMD2 | protein-coding | 221496 |
| MIR3934 | ncRNA | 100500873 |
| UQCC2 | protein-coding | 84300 |
| LINC01016 | ncRNA | 100507584 |
Protein
Protein identifiers
Promotilin — P12872 (reviewed: P12872)
All UniProt accessions (1): P12872
UniProt curated annotations — full annotation on UniProt →
Function. Plays an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle.
Subcellular location. Secreted.
Similarity. Belongs to the motilin family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P12872-1 | 1 | yes |
| P12872-2 | 2 | |
| P12872-3 | 3 |
RefSeq proteins (3): NP_001035198, NP_001171627, NP_002409* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR006737 | Motilin_assoc | Domain |
| IPR006738 | Motilin_ghrelin | Domain |
| IPR015662 | Promotilin | Family |
Pfam: PF04643, PF04644
UniProt features (9 total): peptide 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, sequence variant 1, helix 1
Structure
Experimental structures (PDB)
2 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 8IBV | Cryo-EM structure of the motilin-bound motilin receptor-Gq protein complex | ELECTRON MICROSCOPY | 3.19 |
| 1LBJ | NMR solution structure of motilin in phospholipid bicellar solution | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P12872-F1 | 68.67 | 0.08 |
Antibody-complex structures (SAbDab)
1 antibodies co-crystallized with this protein: 8IBV
Human Protein Atlas
Protein class: Predicted secreted proteins
Protein evidence: Evidence at protein level
Antibody reliability (HPA): IH enhanced
Function
Pathways and Gene Ontology
Reactome pathways
2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
7 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-416476 | G alpha (q) signalling events | curated |
| R-HSA-375276 | Peptide ligand-binding receptors | curated |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | — |
| R-HSA-388396 | GPCR downstream signalling | — |
| R-HSA-500792 | GPCR ligand binding | — |
| R-HSA-162582 | Signal Transduction | — |
| R-HSA-372790 | Signaling by GPCR | — |
MSigDB gene sets: 53 (showing top):
MORF_ATRX, MORF_ESR1, BROWNE_HCMV_INFECTION_48HR_DN, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MORF_ETV3, AACTTT_UNKNOWN, MYB_Q3, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_BINDING, MORF_MT4, GCM_LTK, MYB_Q5_01, MORF_MYC, GOMF_HORMONE_ACTIVITY, MORF_PAX7
GO Biological Process (1): signal transduction (GO:0007165)
GO Molecular Function (3): hormone activity (GO:0005179), motilin receptor binding (GO:0031788), protein binding (GO:0005515)
GO Cellular Component (1): extracellular region (GO:0005576)
Reactome top-level categories
5 top-level categories:
| Category | Pathways |
|---|---|
| Signaling by GPCR | 2 |
| Class A/1 (Rhodopsin-like receptors) | 1 |
| GPCR downstream signalling | 1 |
| Signal Transduction | 1 |
| GPCR ligand binding | 1 |
GO top-level categories
9 GO namespaces:
| Category | Terms |
|---|---|
| cell communication | 1 |
| cellular process | 1 |
| signaling | 1 |
| regulation of cellular process | 1 |
| cellular response to stimulus | 1 |
| receptor ligand activity | 1 |
| G protein-coupled receptor binding | 1 |
| binding | 1 |
| cellular anatomical structure | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).
1 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| motilin receptor binding | MF | physical interaction |
Protein interactions and networks
STRING
showing 15 of 644 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| MLN | MLNR | O43193 | 988 |
| MLN | GAST | P01350 | 886 |
| MLN | GHRL | Q9UBU3 | 836 |
| MLN | PPY | P01298 | 833 |
| MLN | GHSR | Q92847 | 828 |
| MLN | SST | P01166 | 825 |
| MLN | NTS | P30990 | 824 |
| MLN | CCK | P06307 | 810 |
| MLN | GPR39 | O43194 | 800 |
| MLN | SCT | P09683 | 796 |
| MLN | VIP | P01282 | 779 |
| MLN | TUBB6 | Q9BUF5 | 760 |
| MLN | TUBB8 | Q3ZCM7 | 760 |
| MLN | TUBB4A | P04350 | 759 |
| MLN | TUBB4B | P05217 | 758 |
IntAct
Human interaction partners of MLN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
2 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| TMX2 | physical association | 0.560 | 3 |
| TTC19 | physical association | 0.560 | 3 |
BioGRID (2 interactions; top human partners by supporting records): TMX2 (Two-hybrid), TTC19 (Two-hybrid)
SIGNOR signaling
1 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| MLN | up-regulates | MLNR | binding |
Disease & clinical
Genetic variants
Variant evidence for MLN: 19 ClinVar records (0 pathogenic / likely pathogenic).
ClinVar
19 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 17 |
| Likely benign | 0 |
| Benign | 0 |
AlphaMissense
35 missense substitutions predicted likely pathogenic (of 749 scored), across 19 residues. Top 19 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| F30 | 5 | 0.825 | 0.924 |
| F26 | 4 | 0.865 | 0.937 |
| I29 | 3 | 0.712 | 0.773 |
| P28 | 3 | 0.604 | 0.620 |
| K48 | 2 | 0.659 | 0.659 |
| K5 | 2 | 0.605 | 0.605 |
| Q39 | 2 | 0.589 | 0.589 |
| Q93 | 2 | 0.580 | 0.580 |
| L10 | 2 | 0.576 | 0.583 |
| V27 | 1 | 0.732 | 0.732 |
| T31 | 1 | 0.728 | 0.728 |
| A20 | 1 | 0.683 | 0.683 |
| A16 | 1 | 0.673 | 0.673 |
| R43 | 1 | 0.664 | 0.664 |
| E34 | 1 | 0.637 | 0.637 |
| V13 | 1 | 0.626 | 0.626 |
| L35 | 1 | 0.613 | 0.613 |
| A8 | 1 | 0.609 | 0.609 |
| V12 | 1 | 0.603 | 0.603 |
HPA cancer prognostics
RNA cancer specificity: Group enriched (Pancreatic Adenocarcinoma, Stomach Adenocarcinoma, Testicular Germ Cell Tumor)
Disease associations
OMIM: gene MIM:158270 | disease phenotypes:
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5214853 (SINGLE PROTEIN)
PharmGKB: 1 entry (CPIC guideline: no)
Binding affinities (BindingDB)
35 measured of 36 human assays (36 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| CAS_52906-92-0 | EC50 | 0.0398 nM |
| MOTILIN | EC50 | 0.15 nM |
| NSC_0 | KI | 0.447 nM |
| [leu13]pMOT(1-19) | KI | 0.98 nM |
| [leu13]pMOT(1-22) | KI | 1 nM |
| [ala3,leu13]pMOT(1-14) | KI | 1.32 nM |
| [leu13]pMOT(1-16) | KI | 2.14 nM |
| [leu13]pMOT(1-14) | KI | 3.16 nM |
| [ala11,leu13]pMOT(1-14) | KI | 4.57 nM |
| [ala10,leu13]pMOT(1-14) | KI | 5.01 nM |
| N-ethyl, N-methyl Erythromycin-A enol ether | KI | 6.03 nM |
| [ala12,leu13]pMOT(1-14) | KI | 6.31 nM |
| [ala14,leu13]pMOT(1-14) | KI | 7.08 nM |
| [ala13,leu13]pMOT(1-14) | KI | 7.24 nM |
| Erythromycin-B enol ether | KI | 7.59 nM |
| [ala5,leu13]pMOT(1-14) | KI | 28.8 nM |
| [ala8,leu13]pMOT(1-14) | KI | 36.3 nM |
| [ala6,leu13]pMOT(1-14) | KI | 46.8 nM |
| [L-Bpa5,Ile13]Motilin | KI | 50 nM |
| ABT-229 | KI | 58.9 nM |
| [ala9,leu13]pMOT(1-14) | KI | 75.9 nM |
| [leu13]pMOT(1-11) | KI | 89.1 nM |
| Erythromycin-B | KI | 145 nM |
| Erythromycin-A enol ether | IC50 | 224 nM |
| N-ethyl, N-Methyl Erythromycin-A | KI | 240 nM |
| EM-B enolether | KI | 324 nM |
| [D-Bpa5,Ile13]Motilin | KI | 420 nM |
| Erythromycin A Enol Ether | KI | 537 nM |
| [ala7,leu13]pMOT(1-14) | KI | 1450 nM |
| [ala4,leu13]pMOT(1-14) | KI | 2570 nM |
| CAS_114-07-8 | KI | 3090 nM |
| [leu13]pMOT(1-9) | KI | 4070 nM |
| [leu13]pMOT(1-7) | KI | 6920 nM |
| [leu13]pMOT(1-5) | KI | 8910 nM |
| (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-{[(2R,3S,4R,6S)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione | IC50 | 72400 nM |
ChEMBL bioactivities
1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 5.14 | Ki | 7200 | nM | CHEMBL4789678 |
CTD chemical–gene interactions
7 total (human), top 7 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | affects methylation, increases expression | 2 |
| CGP 52608 | affects binding, increases reaction | 1 |
| bisphenol S | increases methylation | 1 |
| Carbamazepine | affects response to substance | 1 |
| Triclosan | increases expression | 1 |
| Valproic Acid | increases methylation | 1 |
| Aflatoxin B1 | increases methylation | 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 |
|---|---|---|---|
| CHEMBL5214700 | Binding | Selectivity interaction (Enzyme panel (ion channels, GPCRs, other targets)) EUB0000196bCl MLN | Selectivity Literature for EUbOPEN Chemogenomics Library wave 3 |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for MLN across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.