Megacystis-microcolon-intestinal hypoperistalsis syndrome 5

Summary

Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 (MONDO:0030329) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	megacystis-microcolon-intestinal hypoperistalsis syndrome 5
Mondo ID	MONDO:0030329
OMIM	619431
UMLS	C5543636
MedGen	1782906
GARD	0027926
Is cancer (heuristic)	no

Also known as: megacystis-microcolon-intestinal hypoperistalsis syndrome 5 · MMIHS5

Data availability: 25 ClinVar variants.

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 5

Related subtypes (4): megacystis-microcolon-intestinal hypoperistalsis syndrome 2, megacystis-microcolon-intestinal hypoperistalsis syndrome 3, megacystis-microcolon-intestinal hypoperistalsis syndrome 4, 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

25 retrieved; paginated sample, class counts are floors:

8 pathogenic, 5 likely pathogenic, 4 benign, 4 uncertain significance, 3 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
132798	NM_001615.4(ACTG2):c.533G>T (p.Arg178Leu)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
132799	NM_001615.4(ACTG2):c.118C>T (p.Arg40Cys)	ACTG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132800	NM_001615.4(ACTG2):c.532C>T (p.Arg178Cys)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
132801	NM_001615.4(ACTG2):c.533G>A (p.Arg178His)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
132802	NM_001615.4(ACTG2):c.119G>A (p.Arg40His)	ACTG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132803	NM_001615.4(ACTG2):c.769C>T (p.Arg257Cys)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
132805	NM_001615.4(ACTG2):c.400T>A (p.Tyr134Asn)	ACTG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208792	NM_001615.4(ACTG2):c.770G>A (p.Arg257His)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
3024243	NM_001615.4(ACTG2):c.532C>A (p.Arg178Ser)	ACTG2	Pathogenic	criteria provided, single submitter
3362785	NM_001615.4(ACTG2):c.413A>G (p.Gln138Arg)	ACTG2	Pathogenic	criteria provided, single submitter
694269	NM_001615.4(ACTG2):c.188G>A (p.Arg63Gln)	ACTG2	Pathogenic	criteria provided, single submitter
1703035	NM_001615.4(ACTG2):c.116C>G (p.Pro39Arg)	ACTG2	Likely pathogenic	criteria provided, single submitter
1709289	NM_001615.4(ACTG2):c.188G>T (p.Arg63Leu)	ACTG2	Likely pathogenic	criteria provided, single submitter
1803217	NM_001615.4(ACTG2):c.593G>T (p.Gly198Val)	ACTG2	Likely pathogenic	criteria provided, single submitter
3065144	NM_001615.4(ACTG2):c.1007G>A (p.Arg336Gln)	ACTG2	Likely pathogenic	criteria provided, single submitter
3256572	NM_001615.4(ACTG2):c.464A>G (p.Asp155Gly)	ACTG2	Likely pathogenic	criteria provided, single submitter
2572538	NM_001615.4(ACTG2):c.131T>A (p.Val44Glu)	ACTG2	Uncertain significance	criteria provided, single submitter
2664268	NM_001615.4(ACTG2):c.359T>C (p.Met120Thr)	ACTG2	Uncertain significance	no assertion criteria provided
2664269	NM_001615.4(ACTG2):c.985A>C (p.Lys329Gln)	ACTG2	Uncertain significance	no assertion criteria provided
3362480	NM_001615.4(ACTG2):c.104T>C (p.Ile35Thr)	ACTG2	Uncertain significance	criteria provided, single submitter
1188856	NM_001615.4(ACTG2):c.-6C>T	ACTG2	Benign	criteria provided, multiple submitters, no conflicts
1188857	NM_001615.4(ACTG2):c.256-3T>C	ACTG2	Benign	criteria provided, multiple submitters, no conflicts
1188998	NM_001615.4(ACTG2):c.-36-12G>C	ACTG2	Benign	criteria provided, multiple submitters, no conflicts
4795842	NM_001615.4(ACTG2):c.724G>A (p.Glu242Lys)	ACTG2	Likely benign	criteria provided, single submitter
801724	NM_001615.4(ACTG2):c.354A>G (p.Glu118=)	ACTG2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTG2	Orphanet:104077	Myopathic intestinal pseudoobstruction
ACTG2	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
ACTG2	Orphanet:2604	Familial visceral myopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACTG2	HGNC:145	ENSG00000163017	P63267	Actin, gamma-enteric smooth muscle	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTG2	Actin, gamma-enteric smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTG2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cauda epididymis	1
saphenous vein	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTG2	241	broad	marker	seminal vesicle, cauda epididymis, saphenous vein

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACTG2	133

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTG2	P63267	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of CDH1 Function	1	951.7×	0.007	ACTG2
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.009	ACTG2
Smooth Muscle Contraction	1	265.6×	0.009	ACTG2
Activation of STAT3 by cadherin engagement	1	163.1×	0.009	ACTG2
Non-integrin membrane-ECM interactions	1	154.3×	0.009	ACTG2
Muscle contraction	1	77.2×	0.015	ACTG2
Extracellular matrix organization	1	63.1×	0.016	ACTG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesenchyme migration	1	3370.4×	7e-04	ACTG2
cellular response to acetaldehyde	1	3370.4×	7e-04	ACTG2
cellular response to interleukin-6	1	991.3×	0.002	ACTG2
response to ethanol	1	146.5×	0.009	ACTG2
positive regulation of gene expression	1	38.7×	0.026	ACTG2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTG2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 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.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	ACTG2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ACTG2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.