Isolated agenesis of gallbladder

Summary

Isolated agenesis of gallbladder (MONDO:0007642) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	25	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated agenesis of gallbladder
Mondo ID	MONDO:0007642
MeSH	C562564
OMIM	137040
Orphanet	440987
UMLS	C0266251
MedGen	82736
GARD	0021844
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › biliary tract disorder › isolated agenesis of gallbladder

Related subtypes (14): bile duct disorder, biliary tract neoplasm, gallstones, primary biliary cholangitis, bile reflux, postcholecystectomy syndrome, Alagille syndrome, cholelithiasis, ketamine-induced biliary dilatation, follicular cholangitis and pancreatitis, idiopathic ductopenia, Caroli syndrome, isolated congenital hepatic fibrosis, Rokitansky-Aschoff sinuses of the gallbladder

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
523483	NM_005378.6(MYCN):c.1226C>T (p.Pro409Leu)	MYCN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYCN	Orphanet:357027	Hereditary retinoblastoma
MYCN	Orphanet:357034	Non-hereditary retinoblastoma
MYCN	Orphanet:391641	Feingold syndrome type 1
MYCN	Orphanet:635	Neuroblastoma

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
MYCN	HGNC:7559	ENSG00000134323	P04198	N-myc proto-oncogene protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYCN	N-myc proto-oncogene protein	Positively regulates the transcription of MYCNOS in neuroblastoma cells.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYCN	Transcription factor	no		Tscrpt_reg_Myc, bHLH_dom, Tscrpt_reg_Myc_N

Expression context

Cohort genes with no expression data: 0.

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
cortical plate	1
embryo	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYCN	223	broad	yes	ventricular zone, cortical plate, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYCN	7,345

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYCN	P04198	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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 mRNA translation by microRNAs	1	1038.2×	0.005	MYCN
Signaling by ALK	1	571.0×	0.005	MYCN
TGFBR3 expression	1	456.8×	0.005	MYCN
Signaling by TGFBR3	1	368.4×	0.005	MYCN
Signaling by TGFB family members	1	115.3×	0.012	MYCN
Regulation of PD-L1(CD274) transcription	1	108.8×	0.012	MYCN
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.022	MYCN
Signal Transduction	1	10.2×	0.098	MYCN

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 inner ear auditory receptor cell differentiation	1	5617.3×	0.003	MYCN
autosome genomic imprinting	1	2407.4×	0.003	MYCN
negative regulation of astrocyte differentiation	1	1532.0×	0.003	MYCN
positive regulation of programmed cell death	1	1123.5×	0.003	MYCN
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.003	MYCN
cartilage condensation	1	766.0×	0.003	MYCN
astrocyte differentiation	1	766.0×	0.003	MYCN
branching morphogenesis of an epithelial tube	1	732.7×	0.003	MYCN
positive regulation of mesenchymal cell proliferation	1	601.9×	0.004	MYCN
embryonic skeletal system morphogenesis	1	391.9×	0.005	MYCN
epithelial cell proliferation	1	312.1×	0.005	MYCN
embryonic digit morphogenesis	1	300.9×	0.005	MYCN
positive regulation of miRNA transcription	1	290.6×	0.005	MYCN
positive regulation of epithelial cell proliferation	1	244.2×	0.006	MYCN
lung development	1	198.3×	0.007	MYCN
negative regulation of gene expression	1	69.1×	0.018	MYCN
positive regulation of gene expression	1	38.7×	0.030	MYCN
positive regulation of DNA-templated transcription	1	27.9×	0.040	MYCN
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	MYCN
regulation of transcription by RNA polymerase II	1	11.7×	0.086	MYCN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYCN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MYCN	11	Binding:11

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	MYCN

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)
MYCN	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.