Megacystis-microcolon-intestinal hypoperistalsis syndrome 2
diseaseOn this page
Also known as MMIHS2
Summary
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (MONDO:0025708) is a disease caused by MYH11 (GenCC Strong), with 3 cohort genes.
At a glance
- Causal gene: MYH11 (GenCC Strong)
- Cohort genes: 3
- ClinVar variants: 172
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | megacystis-microcolon-intestinal hypoperistalsis syndrome 2 |
| Mondo ID | MONDO:0025708 |
| OMIM | 619351 |
| UMLS | C5543476 |
| MedGen | 1788773 |
| GARD | 0016447 |
| Is cancer (heuristic) | no |
Also known as: MMIHS2
Data availability: 172 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › megacystis-microcolon-intestinal hypoperistalsis syndrome › megacystis-microcolon-intestinal hypoperistalsis syndrome 2
Related subtypes (4): megacystis-microcolon-intestinal hypoperistalsis syndrome 3, megacystis-microcolon-intestinal hypoperistalsis syndrome 4, megacystis-microcolon-intestinal hypoperistalsis syndrome 5, megacystis-microcolon-intestinal hypoperistalsis syndrome 1
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
172 retrieved; paginated sample, class counts are floors:
112 uncertain significance, 30 conflicting classifications of pathogenicity, 10 benign, 6 benign/likely benign, 5 pathogenic, 4 likely benign, 3 likely pathogenic, 2 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1341990 | GRCh37/hg19 16p13.11(chr16:15551302-16194578)x1 | ABCC1 | Pathogenic | criteria provided, single submitter |
| 1120184 | NM_002474.3(MYH11):c.3519_3520delinsTT (p.Glu1173_Gln1174delinsAspTer) | MYH11 | Pathogenic | no assertion criteria provided |
| 1252066 | NM_002474.3(MYH11):c.1033+1G>A | MYH11 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1341984 | NM_002474.3(MYH11):c.3122-2_3124del | MYH11 | Pathogenic | criteria provided, single submitter |
| 156401 | NM_002474.3(MYH11):c.3598A>T (p.Lys1200Ter) | MYH11 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 211548 | NM_002474.3(MYH11):c.3422_3470del (p.Lys1141fs) | MYH11 | Pathogenic | criteria provided, single submitter |
| 3776079 | NM_002474.3(MYH11):c.4435dup (p.Arg1479fs) | MYH11 | Pathogenic | criteria provided, single submitter |
| 2627065 | NM_002474.3(MYH11):c.3424C>T (p.Arg1142Ter) | MYH11 | Likely pathogenic | criteria provided, single submitter |
| 3366318 | NC_000016.9:g.(15797981_15802659)_(15892545_15917111)del | MYH11 | Likely pathogenic | criteria provided, single submitter |
| 3382738 | NM_002474.3(MYH11):c.582C>G (p.Tyr194Ter) | MYH11 | Likely pathogenic | criteria provided, single submitter |
| 1171454 | NM_002474.3(MYH11):c.2426G>A (p.Arg809Lys) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1329442 | NM_002474.3(MYH11):c.2082G>A (p.Leu694=) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 14135 | NM_002474.3(MYH11):c.2135G>A (p.Arg712Gln) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 161317 | NM_002474.3(MYH11):c.739C>T (p.Arg247Cys) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201039 | NM_002474.3(MYH11):c.5528C>T (p.Ser1843Leu) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201057 | NM_002474.3(MYH11):c.2741C>T (p.Ala914Val) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201068 | NM_002474.3(MYH11):c.3928G>A (p.Val1310Met) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201086 | NM_002474.3(MYH11):c.5499G>C (p.Glu1833Asp) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201092 | NM_002474.3(MYH11):c.5767G>A (p.Ala1923Thr) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201100 | NM_001040113.2(MYH11):c.654+1G>A | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 211547 | NM_002474.3(MYH11):c.2809_2810del (p.Arg937fs) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 252514 | NM_002474.3(MYH11):c.1913C>T (p.Ser638Leu) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 257258 | NM_002474.3(MYH11):c.3897C>T (p.Ala1299=) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263518 | NM_002474.3(MYH11):c.3766A>C (p.Lys1256Gln) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263862 | NM_002474.3(MYH11):c.472G>A (p.Ala158Thr) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 318108 | NM_002474.3(MYH11):c.4791+13G>A | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 465745 | NM_002474.3(MYH11):c.5092G>A (p.Ala1698Thr) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 629821 | NM_002474.3(MYH11):c.4117-6T>G | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 807997 | NM_002474.3(MYH11):c.5869G>C (p.Glu1957Gln) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 888295 | NM_002474.3(MYH11):c.3669C>A (p.Asp1223Glu) | MYH11 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| MYH11 | Strong | Autosomal recessive | megacystis-microcolon-intestinal hypoperistalsis syndrome 2 | 10 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MYH11 | Orphanet:2241 | Megacystis-microcolon-intestinal hypoperistalsis syndrome |
| MYH11 | Orphanet:229 | Familial aortic dissection |
| MYH11 | Orphanet:91387 | Familial thoracic aortic aneurysm and aortic dissection |
| MYH11 | Orphanet:98829 | Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) |
| NDE1 | Orphanet:2177 | Hydranencephaly |
| NDE1 | Orphanet:443162 | NDE1-related microhydranencephaly |
| NDE1 | Orphanet:89844 | Lissencephaly syndrome, Norman-Roberts type |
| ABCC1 | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MYH11 | HGNC:7569 | ENSG00000133392 | P35749 | Myosin-11 | gencc,clinvar |
| NDE1 | HGNC:17619 | ENSG00000072864 | Q9NXR1 | Nuclear distribution protein nudE homolog 1 | clinvar |
| ABCC1 | HGNC:51 | ENSG00000103222 | P33527 | Multidrug resistance-associated protein 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MYH11 | Myosin-11 | Muscle contraction. |
| NDE1 | Nuclear distribution protein nudE homolog 1 | Required for centrosome duplication and formation and function of the mitotic spindle. |
| ABCC1 | Multidrug resistance-associated protein 1 | Mediates export of organic anions and drugs from the cytoplasm. |
Protein-family classification
Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Transporter | 1 | 25.9× | 0.114 |
| Scaffold/PPI | 1 | 5.8× | 0.246 |
| Other/Unknown | 1 | 0.6× | 0.914 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MYH11 | Scaffold/PPI | no | IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail | |
| NDE1 | Other/Unknown | no | NUDE_dom, NUDE | |
| ABCC1 | Transporter | yes | 7.6.2.2 | ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP |
Expression context
Cohort genes with no expression data: 0.
3 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| lower esophagus | 2 |
| lower esophagus muscularis layer | 2 |
| right coronary artery | 1 |
| colonic epithelium | 1 |
| corpus callosum | 1 |
| ventricular zone | 1 |
| lower esophagus mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MYH11 | 143 | broad | marker | right coronary artery, lower esophagus, lower esophagus muscularis layer |
| NDE1 | 134 | ubiquitous | marker | colonic epithelium, ventricular zone, corpus callosum |
| ABCC1 | 134 | ubiquitous | marker | lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MYH11 | 3,818 |
| ABCC1 | 3,018 |
| NDE1 | 1,761 |
Structural data
PDB: 3 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ABCC1 | P33527 | 5 |
| MYH11 | P35749 | 1 |
| NDE1 | Q9NXR1 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 69. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Metabolism of porphyrins | 1 | 475.8× | 0.024 | ABCC1 |
| Transport of RCbl within the body | 1 | 475.8× | 0.024 | ABCC1 |
| NFE2L2 regulating MDR associated enzymes | 1 | 475.8× | 0.024 | ABCC1 |
| Heme degradation | 1 | 271.9× | 0.024 | ABCC1 |
| Sema4D in semaphorin signaling | 1 | 223.9× | 0.024 | MYH11 |
| Cobalamin (Cbl, vitamin B12) transport and metabolism | 1 | 211.5× | 0.024 | ABCC1 |
| RHO GTPases activate CIT | 1 | 200.3× | 0.024 | MYH11 |
| RHO GTPases Activate ROCKs | 1 | 200.3× | 0.024 | MYH11 |
| Synthesis of Leukotrienes (LT) and Eoxins (EX) | 1 | 190.3× | 0.024 | ABCC1 |
| Arachidonate metabolism | 1 | 190.3× | 0.024 | ABCC1 |
| Sema4D induced cell migration and growth-cone collapse | 1 | 190.3× | 0.024 | MYH11 |
| RHO GTPases activate PAKs | 1 | 181.3× | 0.024 | MYH11 |
| Developmental Lineage of Mammary Gland Myoepithelial Cells | 1 | 181.3× | 0.024 | MYH11 |
| RHO GTPase Effectors | 2 | 45.3× | 0.024 | MYH11, NDE1 |
| Signaling by Rho GTPases | 2 | 22.8× | 0.024 | MYH11, NDE1 |
| Signaling by Rho GTPases, Miro GTPases and RHOBTB3 | 2 | 22.3× | 0.024 | MYH11, NDE1 |
| Paracetamol ADME | 1 | 141.0× | 0.029 | ABCC1 |
| Semaphorin interactions | 1 | 131.3× | 0.029 | MYH11 |
| EPHA-mediated growth cone collapse | 1 | 126.9× | 0.029 | MYH11 |
| Nuclear events mediated by NFE2L2 | 1 | 112.0× | 0.031 | ABCC1 |
| RHO GTPases activate PKNs | 1 | 105.7× | 0.031 | MYH11 |
| Sphingolipid de novo biosynthesis | 1 | 95.2× | 0.033 | ABCC1 |
| Smooth Muscle Contraction | 1 | 88.5× | 0.034 | MYH11 |
| Centrosome maturation | 1 | 84.6× | 0.034 | NDE1 |
| Drug ADME | 1 | 76.1× | 0.036 | ABCC1 |
| Amplification of signal from the kinetochores | 1 | 65.6× | 0.039 | NDE1 |
| Cytoprotection by HMOX1 | 1 | 61.4× | 0.039 | ABCC1 |
| Metabolism of water-soluble vitamins and cofactors | 1 | 60.4× | 0.039 | ABCC1 |
| Sphingolipid metabolism | 1 | 56.0× | 0.039 | ABCC1 |
| EPH-Ephrin signaling | 1 | 55.2× | 0.039 | MYH11 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| antigen processing and presentation of lipid antigen via MHC class Ib | 1 | 5617.3× | 0.003 | ABCC1 |
| cyclic nucleotide transport | 1 | 5617.3× | 0.003 | ABCC1 |
| sphingolipid translocation | 1 | 5617.3× | 0.003 | ABCC1 |
| intracellular nitrogen homeostasis | 1 | 5617.3× | 0.003 | ABCC1 |
| pigment accumulation | 1 | 2808.7× | 0.005 | ABCC1 |
| chromosome localization | 1 | 2808.7× | 0.005 | NDE1 |
| granuloma formation | 1 | 1872.4× | 0.005 | ABCC1 |
| skeletal muscle myosin thick filament assembly | 1 | 1872.4× | 0.005 | MYH11 |
| glutathione transmembrane transport | 1 | 1404.3× | 0.005 | ABCC1 |
| neural tissue regeneration | 1 | 1404.3× | 0.005 | ABCC1 |
| mitotic centrosome separation | 1 | 936.2× | 0.005 | NDE1 |
| glucocorticoid metabolic process | 1 | 936.2× | 0.005 | ABCC1 |
| amygdala development | 1 | 936.2× | 0.005 | ABCC1 |
| NK T cell activation | 1 | 936.2× | 0.005 | ABCC1 |
| carboxylic acid transmembrane transport | 1 | 936.2× | 0.005 | ABCC1 |
| xenobiotic transport across blood-brain barrier | 1 | 936.2× | 0.005 | ABCC1 |
| leukotriene transport | 1 | 802.5× | 0.005 | ABCC1 |
| lymphocyte migration | 1 | 802.5× | 0.005 | ABCC1 |
| cobalamin transport | 1 | 624.1× | 0.006 | ABCC1 |
| response to fluid shear stress | 1 | 624.1× | 0.006 | ABCC1 |
| export across plasma membrane | 1 | 561.7× | 0.006 | ABCC1 |
| heme catabolic process | 1 | 510.7× | 0.006 | ABCC1 |
| elastic fiber assembly | 1 | 510.7× | 0.006 | MYH11 |
| amyloid-beta metabolic process | 1 | 510.7× | 0.006 | ABCC1 |
| hydrogen peroxide biosynthetic process | 1 | 468.1× | 0.006 | ABCC1 |
| endothelium development | 1 | 432.1× | 0.006 | ABCC1 |
| leukotriene metabolic process | 1 | 432.1× | 0.006 | ABCC1 |
| leukotriene biosynthetic process | 1 | 432.1× | 0.006 | ABCC1 |
| endothelial cell apoptotic process | 1 | 432.1× | 0.006 | ABCC1 |
| transepithelial transport | 1 | 401.2× | 0.006 | ABCC1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2
Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| ABCC1 | RIMONABANT |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ABCC1 | 23 | 4 |
| MYH11 | 0 | 0 |
| NDE1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| RIMONABANT | 4 | ABCC1 |
| VINBLASTINE | 4 | ABCC1 |
| CYCLOSPORINE | 4 | ABCC1 |
| DAUNORUBICIN | 4 | ABCC1 |
| ETRAVIRINE | 4 | ABCC1 |
| BENZBROMARONE | 4 | ABCC1 |
| ESTRONE SULFURIC ACID | 4 | ABCC1 |
| DOXORUBICIN | 4 | ABCC1 |
| MITOXANTRONE | 4 | ABCC1 |
| INDOMETHACIN | 4 | ABCC1 |
| IVERMECTIN | 4 | ABCC1 |
| VERAPAMIL | 4 | ABCC1 |
| VINCRISTINE | 4 | ABCC1 |
| VALSPODAR | 3 | ABCC1 |
| TARIQUIDAR | 3 | ABCC1 |
| QUERCETIN | 3 | ABCC1 |
| DEXVERAPAMIL | 2 | ABCC1 |
| VEDROPREVIR | 2 | ABCC1 |
| VERLUKAST | 2 | ABCC1 |
| BIRICODAR | 2 | ABCC1 |
| CLESACOSTAT | 2 | ABCC1 |
| BMS-754807 | 2 | ABCC1 |
| KAEMPFEROL | 1 | ABCC1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| ABCC1 | 459 | Binding:270, Functional:166, ADMET:23 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ABCC1 | 7.6.2.2, 7.6.2.3 | ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| ABCC1 | 459 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
23 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| RIMONABANT | 4 | ABCC1 |
| VINBLASTINE | 4 | ABCC1 |
| CYCLOSPORINE | 4 | ABCC1 |
| DAUNORUBICIN | 4 | ABCC1 |
| ETRAVIRINE | 4 | ABCC1 |
| BENZBROMARONE | 4 | ABCC1 |
| ESTRONE SULFURIC ACID | 4 | ABCC1 |
| DOXORUBICIN | 4 | ABCC1 |
| MITOXANTRONE | 4 | ABCC1 |
| INDOMETHACIN | 4 | ABCC1 |
| IVERMECTIN | 4 | ABCC1 |
| VERAPAMIL | 4 | ABCC1 |
| VINCRISTINE | 4 | ABCC1 |
| VALSPODAR | 3 | ABCC1 |
| TARIQUIDAR | 3 | ABCC1 |
| QUERCETIN | 3 | ABCC1 |
| DEXVERAPAMIL | 2 | ABCC1 |
| VEDROPREVIR | 2 | ABCC1 |
| VERLUKAST | 2 | ABCC1 |
| BIRICODAR | 2 | ABCC1 |
| CLESACOSTAT | 2 | ABCC1 |
| BMS-754807 | 2 | ABCC1 |
| KAEMPFEROL | 1 | ABCC1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | ABCC1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | MYH11, NDE1 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| MYH11 | 0 | — |
| NDE1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.