Megacystis-microcolon-intestinal hypoperistalsis syndrome 4

Summary

Megacystis-microcolon-intestinal hypoperistalsis syndrome 4 (MONDO:0030296) is a disease caused by MYL9 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MYL9 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	megacystis-microcolon-intestinal hypoperistalsis syndrome 4
Mondo ID	MONDO:0030296
OMIM	619365
UMLS	C5543519
MedGen	1783600
GARD	0027925
Is cancer (heuristic)	no

Also known as: megacystis-microcolon-intestinal hypoperistalsis syndrome 4 · MMIHS4

Data availability: 1 ClinVar variant · 3 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 4

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
818204	NM_006097.5(MYL9):c.184+2_184+10del	DLGAP4-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
MYL9	Strong	Autosomal recessive	megacystis-microcolon-intestinal hypoperistalsis syndrome 4	3

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYL9	HGNC:15754	ENSG00000101335	P24844	Myosin regulatory light polypeptide 9	gencc
DLGAP4-AS1	HGNC:51223	ENSG00000232907		DLGAP4 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYL9	Myosin regulatory light polypeptide 9	Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYL9	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
DLGAP4-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
popliteal artery	1
right coronary artery	1
tibial artery	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYL9	263	ubiquitous	marker	popliteal artery, tibial artery, right coronary artery
DLGAP4-AS1	161	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYL9	3,272
DLGAP4-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYL9	P24844	84.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 2 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
Sema4D in semaphorin signaling	1	671.8×	0.008	MYL9
RHO GTPases activate CIT	1	601.0×	0.008	MYL9
RHO GTPases Activate ROCKs	1	601.0×	0.008	MYL9
Sema4D induced cell migration and growth-cone collapse	1	571.0×	0.008	MYL9
RHO GTPases activate PAKs	1	543.8×	0.008	MYL9
Semaphorin interactions	1	393.8×	0.009	MYL9
EPHA-mediated growth cone collapse	1	380.7×	0.009	MYL9
RHO GTPases activate PKNs	1	317.2×	0.009	MYL9
Smooth Muscle Contraction	1	265.6×	0.010	MYL9
EPH-Ephrin signaling	1	165.5×	0.014	MYL9
Transcriptional regulation by RUNX1	1	146.4×	0.014	MYL9
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.016	MYL9
Muscle contraction	1	77.2×	0.023	MYL9
RHO GTPase Effectors	1	68.0×	0.024	MYL9
Axon guidance	1	45.1×	0.033	MYL9
Nervous system development	1	42.9×	0.033	MYL9
Signaling by Rho GTPases	1	34.2×	0.038	MYL9
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	MYL9
RNA Polymerase II Transcription	1	22.5×	0.054	MYL9
Gene expression (Transcription)	1	17.8×	0.064	MYL9
Generic Transcription Pathway	1	15.1×	0.072	MYL9
Developmental Biology	1	14.5×	0.072	MYL9
Signal Transduction	1	10.2×	0.098	MYL9

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
regulation of muscle contraction	1	1685.2×	0.002	MYL9
myofibril assembly	1	1123.5×	0.002	MYL9
stress fiber assembly	1	766.0×	0.002	MYL9
platelet aggregation	1	337.0×	0.003	MYL9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MYL9	0	0
DLGAP4-AS1	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	2	MYL9, DLGAP4-AS1

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)
MYL9	0	—
DLGAP4-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.