Maturity-onset diabetes of the young type 6

Summary

Maturity-onset diabetes of the young type 6 (MONDO:0011668) is a disease caused by NEUROD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NEUROD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 112

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	maturity-onset diabetes of the young type 6
Mondo ID	MONDO:0011668
MeSH	C565231
OMIM	606394
DOID	DOID:0111104
NCIT	C129745
SNOMED CT	609573005
UMLS	C1853371
MedGen	344030
GARD	0010660
Is cancer (heuristic)	no

Also known as: diabetes mellitus MODY type 6 · maturity onset diabetes of the Young, type 6 · maturity-onset diabetes of the young (disease) caused by mutation in NEUROD1 · maturity-onset diabetes of the young 6 · maturity-onset diabetes of the young, type 6 · MODY NEUROD1 related · MODY6 · NEUROD1 maturity-onset diabetes of the young (disease) · NEUROD1-associated monogenic diabetes · neurogenic differentiation Factor 1-associated monogenic diabetes · type 6 maturity-onset diabetes of the young

Data availability: 112 ClinVar variants · 5 GenCC gene-disease records.

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 6

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 8, maturity-onset diabetes of the young type 7, maturity-onset diabetes of the young type 9, 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

112 retrieved; paginated sample, class counts are floors:

84 uncertain significance, 9 likely benign, 7 conflicting classifications of pathogenicity, 7 benign, 3 benign/likely benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
218145	NM_002500.5(NEUROD1):c.309C>G (p.Arg103=)	NEUROD1	Pathogenic	no assertion criteria provided
4540411	NM_002500.5(NEUROD1):c.328G>C (p.Glu110Gln)	NEUROD1	Likely pathogenic	criteria provided, single submitter
129763	NM_002500.5(NEUROD1):c.590C>A (p.Pro197His)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2962458	NM_002500.5(NEUROD1):c.36C>T (p.Gly12=)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
333036	NM_002500.5(NEUROD1):c.973C>A (p.Arg325Ser)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
7854	NM_002500.5(NEUROD1):c.616dup (p.His206fs)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837463	NM_002500.5(NEUROD1):c.357G>A (p.Ala119=)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896247	NM_002500.5(NEUROD1):c.964G>A (p.Ala322Thr)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
899007	NM_002500.5(NEUROD1):c.34G>C (p.Gly12Arg)	NEUROD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001015	NM_002500.5(NEUROD1):c.616C>A (p.His206Asn)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1001142	NM_002500.5(NEUROD1):c.1031G>A (p.Arg344Gln)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014823	NM_002500.5(NEUROD1):c.284G>A (p.Arg95His)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1019474	NM_002500.5(NEUROD1):c.222GGA[1] (p.Glu75del)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1026908	NM_002500.5(NEUROD1):c.794C>G (p.Thr265Ser)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1038985	NM_002500.5(NEUROD1):c.758T>C (p.Leu253Pro)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1053839	NM_002500.5(NEUROD1):c.917C>T (p.Ala306Val)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1059324	NM_002500.5(NEUROD1):c.814C>A (p.Pro272Thr)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1307264	NM_002500.5(NEUROD1):c.1055C>T (p.Ala352Val)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1367987	NM_002500.5(NEUROD1):c.616C>G (p.His206Asp)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1369525	NM_002500.5(NEUROD1):c.112A>G (p.Lys38Glu)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1414018	NM_002500.5(NEUROD1):c.487C>T (p.Pro163Ser)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1417052	NM_002500.5(NEUROD1):c.761A>C (p.Glu254Ala)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1438002	NM_002500.5(NEUROD1):c.79C>T (p.Leu27Phe)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1462185	NM_002500.5(NEUROD1):c.746A>G (p.Tyr249Cys)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1490822	NM_002500.5(NEUROD1):c.86C>G (p.Ser29Cys)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1493150	NM_002500.5(NEUROD1):c.94G>A (p.Glu32Lys)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1503008	NM_002500.5(NEUROD1):c.175G>C (p.Glu59Gln)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1506659	NM_002500.5(NEUROD1):c.1043C>T (p.Ala348Val)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1956507	NM_002500.5(NEUROD1):c.714T>G (p.His238Gln)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1962103	NM_002500.5(NEUROD1):c.29T>C (p.Leu10Pro)	NEUROD1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
NEUROD1	Strong	Autosomal recessive	permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEUROD1	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
NEUROD1	HGNC:7762	ENSG00000162992	Q13562	Neurogenic differentiation factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEUROD1	Neurogenic differentiation factor 1	Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5’-CANNTG-3'.

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)
NEUROD1	Transcription factor	no		bHLH_dom, TF_bHLH_NeuroD, NeuroD_DUF

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
cerebellar vermis	1
cerebellum	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEUROD1	115	broad	marker	paraflocculus, cerebellar vermis, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEUROD1	2,901

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEUROD1	Q13562	62.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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×	0.002	NEUROD1
Regulation of beta-cell development	1	713.8×	0.003	NEUROD1
Regulation of gene expression in beta cells	1	519.1×	0.003	NEUROD1
Developmental Biology	1	14.5×	0.069	NEUROD1

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 intestinal epithelial structure maintenance	1	16852.0×	0.001	NEUROD1
pancreatic A cell fate commitment	1	8426.0×	0.001	NEUROD1
pancreatic PP cell fate commitment	1	8426.0×	0.001	NEUROD1
enteroendocrine cell differentiation	1	4213.0×	0.001	NEUROD1
embryonic organ morphogenesis	1	4213.0×	0.001	NEUROD1
negative regulation of type B pancreatic cell apoptotic process	1	2106.5×	0.002	NEUROD1
amacrine cell differentiation	1	1532.0×	0.003	NEUROD1
endocrine pancreas development	1	936.2×	0.004	NEUROD1
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.004	NEUROD1
signal transduction involved in regulation of gene expression	1	702.2×	0.004	NEUROD1
sensory organ development	1	674.1×	0.004	NEUROD1
dentate gyrus development	1	624.1×	0.004	NEUROD1
cellular response to glucocorticoid stimulus	1	624.1×	0.004	NEUROD1
obsolete positive regulation of DNA-binding transcription factor activity	1	601.9×	0.004	NEUROD1
axon development	1	455.5×	0.004	NEUROD1
insulin secretion	1	432.1×	0.004	NEUROD1
regulation of insulin secretion	1	391.9×	0.005	NEUROD1
inner ear development	1	374.5×	0.005	NEUROD1
cerebellum development	1	358.6×	0.005	NEUROD1
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.005	NEUROD1
positive regulation of cell differentiation	1	267.5×	0.005	NEUROD1
response to glucose	1	255.3×	0.005	NEUROD1
positive regulation of insulin secretion	1	255.3×	0.005	NEUROD1
neurogenesis	1	208.1×	0.006	NEUROD1
positive regulation of neuron differentiation	1	198.3×	0.006	NEUROD1
anterior/posterior pattern specification	1	181.2×	0.007	NEUROD1
glucose homeostasis	1	130.6×	0.009	NEUROD1
transcription by RNA polymerase II	1	70.5×	0.016	NEUROD1
positive regulation of apoptotic process	1	56.7×	0.019	NEUROD1
positive regulation of DNA-templated transcription	1	27.9×	0.037	NEUROD1

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
NEUROD1	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	NEUROD1

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)
NEUROD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.