Islet cell adenomatosis

Summary

Islet cell adenomatosis (MONDO:0007834) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	islet cell adenomatosis
Mondo ID	MONDO:0007834
MeSH	C563258
OMIM	147630
NCIT	C4375
SNOMED CT	274944000
UMLS	C1578917
MedGen	293643
Is cancer (heuristic)	no

Also known as: INSDM · islet cell adenomatosis

Data availability: 8 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › islet cell adenomatosis

Related subtypes (11): gastrin secretion abnormality, abnormality of glucagon secretion, hyperinsulinism, post-surgical hypoinsulinemia, pancreatic cholera, diabetes mellitus, aggressive insulitis, benign insulitis, pancreatic neuroendocrine neoplasm, insulin-resistance syndrome type A, insulin-resistance syndrome type B

Subtypes (1): congenital isolated hyperinsulinism

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

8 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2578034	NM_201589.4(MAFA):c.170C>G (p.Thr57Arg)	MAFA	Pathogenic	criteria provided, single submitter
496645	NM_201589.4(MAFA):c.191C>T (p.Ser64Phe)	MAFA	Likely pathogenic	criteria provided, single submitter
1803218	NM_201589.4(MAFA):c.121T>G (p.Phe41Val)	MAFA	Uncertain significance	criteria provided, single submitter
2443167	NM_201589.4(MAFA):c.594CCA[7] (p.His206_His208del)	MAFA	Uncertain significance	criteria provided, single submitter
3242207	NM_201589.4(MAFA):c.631G>A (p.Ala211Thr)	MAFA	Uncertain significance	criteria provided, multiple submitters, no conflicts
3392479	NM_201589.4(MAFA):c.413C>A (p.Ala138Glu)	MAFA	Uncertain significance	criteria provided, single submitter
4292110	NM_201589.4(MAFA):c.182C>T (p.Ser61Phe)	MAFA	Uncertain significance	criteria provided, single submitter
2503478	NM_201589.4(MAFA):c.796G>T (p.Gly266Cys)	MAFA	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
MAFA	HGNC:23145	ENSG00000182759	Q8NHW3	Transcription factor MafA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAFA	Transcription factor MafA	Transcription factor that activates insulin gene expression.

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)
MAFA	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf

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
gastrocnemius	1
hindlimb stylopod muscle	1
quadriceps femoris	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAFA	89	broad	marker	quadriceps femoris, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAFA	478

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAFA	Q8NHW3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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 beta-cell development	1	713.8×	0.003	MAFA
Regulation of gene expression in beta cells	1	519.1×	0.003	MAFA
Developmental Biology	1	14.5×	0.069	MAFA

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
insulin secretion	1	432.1×	0.010	MAFA
response to glucose	1	255.3×	0.010	MAFA
regulation of DNA-templated transcription	1	31.6×	0.053	MAFA
positive regulation of transcription by RNA polymerase II	1	14.9×	0.084	MAFA
regulation of transcription by RNA polymerase II	1	11.7×	0.086	MAFA

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
MAFA	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	MAFA

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)
MAFA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.