Maturity-onset diabetes of the young type 9

Summary

Maturity-onset diabetes of the young type 9 (MONDO:0012818) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	maturity-onset diabetes of the young type 9
Mondo ID	MONDO:0012818
MeSH	C567393
OMIM	612225
DOID	DOID:0111107
SNOMED CT	609576002
UMLS	C2677132
MedGen	383033
GARD	0010663
Is cancer (heuristic)	no

Also known as: diabetes mellitus MODY type 9 · maturity-onset diabetes of the young (disease) caused by mutation in PAX4 · maturity-onset diabetes of the young, type 9 · maturity-onset diabetes of the young, type IX · MODY PAX4 related · MODY type 9 · MODY9 · PAX4 maturity-onset diabetes of the young (disease) · type 9 maturity-onset diabetes of the young

Data availability: 34 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › diabetes mellitus › monogenic diabetes › maturity-onset diabetes of the young › maturity-onset diabetes of the young type 9

Related subtypes (14): maturity-onset diabetes of the young type 1, maturity-onset diabetes of the young type 2, renal cysts and diabetes syndrome, maturity-onset diabetes of the young type 3, maturity-onset diabetes of the young type 4, maturity-onset diabetes of the young type 6, maturity-onset diabetes of the young type 8, maturity-onset diabetes of the young type 7, maturity-onset diabetes of the young type 10, maturity-onset diabetes of the young type 11, Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young, maturity-onset diabetes of the young type 13, maturity-onset diabetes of the young type 14, maturity-onset diabetes of the young, type 12

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

34 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 5 benign/likely benign, 4 likely benign, 3 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1345146	NM_001366110.1(PAX4):c.1013C>T (p.Ala338Val)	PAX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13792	NM_001366110.1(PAX4):c.133C>T (p.Arg45Trp)	PAX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
549523	NM_001366110.1(PAX4):c.211G>T (p.Gly71Cys)	PAX4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129874	NM_001366110.1(PAX4):c.515G>A (p.Arg172Gln)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1315885	NM_001366110.1(PAX4):c.179G>A (p.Arg60His)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1316203	NM_001366110.1(PAX4):c.676C>T (p.Arg226Cys)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1318473	NM_001366110.1(PAX4):c.134G>A (p.Arg45Gln)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1359441	NM_001366110.1(PAX4):c.771+6C>T	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
13793	NM_001366110.1(PAX4):c.514C>T (p.Arg172Trp)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
13794	NM_001366110.1(PAX4):c.772-1G>A	PAX4	Uncertain significance	criteria provided, single submitter
1381394	NM_001366110.1(PAX4):c.488G>A (p.Arg163Gln)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1448516	NM_001366110.1(PAX4):c.638C>T (p.Thr213Met)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803877	NM_001366110.1(PAX4):c.-101_-100+2del	PAX4	Uncertain significance	criteria provided, single submitter
2236365	NM_001366110.1(PAX4):c.677G>A (p.Arg226His)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2502166	NM_001366110.1(PAX4):c.454G>A (p.Val152Ile)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2502226	NM_001366110.1(PAX4):c.779dup (p.Gly261fs)	PAX4	Uncertain significance	criteria provided, single submitter
2580177	NM_001366110.1(PAX4):c.225C>G (p.Ser75Arg)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584566	NM_001366110.1(PAX4):c.574_588del (p.Gly192_Asp196del)	PAX4	Uncertain significance	criteria provided, single submitter
358802	NM_001366110.1(PAX4):c.572G>A (p.Arg191His)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
358807	NM_001366110.1(PAX4):c.260G>A (p.Arg87Gln)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594293	NM_001366110.1(PAX4):c.380T>A (p.Val127Asp)	PAX4	Uncertain significance	criteria provided, single submitter
3891908	NM_001366110.1(PAX4):c.706C>G (p.Gln236Glu)	PAX4	Uncertain significance	criteria provided, single submitter
393408	NM_001366110.1(PAX4):c.932C>T (p.Pro311Leu)	PAX4	Uncertain significance	criteria provided, multiple submitters, no conflicts
438677	NM_001366110.1(PAX4):c.539G>A (p.Ser180Asn)	PAX4	Uncertain significance	no assertion criteria provided
1201272	NM_001366110.1(PAX4):c.636C>T (p.Asp212=)	PAX4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1320922	NM_001366110.1(PAX4):c.69T>C (p.Pro23=)	PAX4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1336936	NM_001366110.1(PAX4):c.762C>T (p.Ile254=)	PAX4	Likely benign	criteria provided, multiple submitters, no conflicts
1570070	NM_001366110.1(PAX4):c.345G>A (p.Gln115=)	PAX4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1571696	NM_001366110.1(PAX4):c.498C>T (p.His166=)	PAX4	Likely benign	criteria provided, multiple submitters, no conflicts
1583240	NM_001366110.1(PAX4):c.116G>T (p.Arg39Leu)	PAX4	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
PAX4	Supportive	Autosomal dominant	maturity-onset diabetes of the young	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX4	Orphanet:552	MODY

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
PAX4	HGNC:8618	ENSG00000106331	O43316	Paired box protein Pax-4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX4	Paired box protein Pax-4	Plays an important role in the differentiation and development of pancreatic islet beta 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)
PAX4	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

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
Brodmann (1909) area 10	1
cerebellar vermis	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX4	32	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, cerebellar vermis, Brodmann (1909) area 10

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX4	1,760

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX4	O43316	70.35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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 gene expression in endocrine-committed (NEUROG3+) progenitor cells	1	2284.0×	4e-04	PAX4

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
type B pancreatic cell differentiation	1	2106.5×	0.003	PAX4
sensory organ development	1	674.1×	0.005	PAX4
forebrain development	1	351.1×	0.007	PAX4
retina development in camera-type eye	1	255.3×	0.007	PAX4
animal organ morphogenesis	1	191.5×	0.007	PAX4
brain development	1	79.5×	0.015	PAX4
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PAX4

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
PAX4	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	PAX4

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)
PAX4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.