Maturity-onset diabetes of the young type 8

Summary

Maturity-onset diabetes of the young type 8 (MONDO:0012348) is a disease caused by CEL (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CEL (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 155

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	maturity-onset diabetes of the young type 8
Mondo ID	MONDO:0012348
MeSH	C565225
OMIM	609812
DOID	DOID:0111105
SNOMED CT	609575003
UMLS	C1853297
MedGen	342845
GARD	0010662
Is cancer (heuristic)	no

Also known as: CEL maturity-onset diabetes of the young (disease) · diabetes mellitus MODY type 8 · DPED · maturity-onset diabetes of the young (disease) caused by mutation in CEL · maturity-onset diabetes of the young, type 8 · maturity-onset diabetes of the young, type 8, with exocrine dysfunction · maturity-onset diabetes of the young, type VIII · MODY8 · type 8 maturity-onset diabetes of the young

Data availability: 155 ClinVar variants · 4 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 8

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 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

155 retrieved; paginated sample, class counts are floors:

111 uncertain significance, 16 conflicting classifications of pathogenicity, 15 likely benign, 4 benign/likely benign, 4 likely pathogenic, 3 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17600	NM_001807.6(CEL):c.1677del (p.Val560fs)	CEL	Pathogenic	no assertion criteria provided
3383345	NC_000009.11:g.(135939771_135947171)del	CEL	Pathogenic	criteria provided, single submitter
2438974	NM_001807.6(CEL):c.1875del (p.Val626fs)	CEL	Likely pathogenic	criteria provided, single submitter
35815	NM_001807.6(CEL):c.1776del (p.Val593fs)	CEL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3596587	NM_001807.6(CEL):c.2139dup (p.Val714fs)	CEL	Likely pathogenic	criteria provided, single submitter
828119	NM_001807.6(CEL):c.703C>T (p.Arg235Ter)	CEL	Likely pathogenic	criteria provided, single submitter
1201063	NM_001807.6(CEL):c.466_479del (p.Val156fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128687	NM_001807.6(CEL):c.1960T>G (p.Ser654Ala)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301626	NM_001807.6(CEL):c.337C>T (p.Gln113Ter)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676816	NM_001807.6(CEL):c.400G>A (p.Gly134Ser)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2456712	NM_001807.6(CEL):c.73G>A (p.Ala25Thr)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2502160	NM_001807.6(CEL):c.1427A>G (p.Gln476Arg)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2584560	NM_001807.6(CEL):c.1410_1411delinsACTC (p.Thr471fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290893	NM_001807.6(CEL):c.2172del (p.Val725fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3141901	NM_001807.6(CEL):c.874G>T (p.Val292Leu)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3237401	NM_001807.6(CEL):c.382G>A (p.Ala128Thr)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3383333	NM_001807.6(CEL):c.2073dup (p.Val692fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779041	NM_001807.6(CEL):c.2065G>C (p.Ala689Pro)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3893039	NM_001807.6(CEL):c.1801del (p.Ala601fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
549532	NM_001807.6(CEL):c.358G>A (p.Val120Ile)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
917438	NM_001807.6(CEL):c.850C>G (p.Arg284Gly)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
917572	NM_001807.6(CEL):c.1974del (p.Val659fs)	CEL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030479	NM_001807.6(CEL):c.1402G>A (p.Ala468Thr)	CEL	Uncertain significance	criteria provided, single submitter
1032004	NM_001807.6(CEL):c.2029G>T (p.Gly677Trp)	CEL	Uncertain significance	criteria provided, single submitter
128691	NM_001807.6(CEL):c.2092T>G (p.Ser698Ala)	CEL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1302296	NM_001807.6(CEL):c.1673_1684delinsGTTCCATGCCCT (p.Thr558_Pro562delinsSerSerMetProSer)	CEL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1308042	NM_001807.6(CEL):c.878C>T (p.Pro293Leu)	CEL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677928	NM_001807.6(CEL):c.895+2dup	CEL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803447	NM_001807.6(CEL):c.1412C>T (p.Thr471Met)	CEL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803880	Single allele	CEL	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
CEL	Strong	Autosomal dominant	maturity-onset diabetes of the young type 8	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEL	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
CEL	HGNC:1848	ENSG00000170835	P19835	Bile salt-activated lipase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEL	Bile salt-activated lipase	Catalyzes the hydrolysis of a wide range of substrates including cholesteryl esters, phospholipids, lysophospholipids, di- and tri-acylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEL	Enzyme (other)	yes	3.1.1.13	CarbesteraseB, Carboxylesterase_B_CS, Carboxylesterase_B_AS

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
body of pancreas	1
pancreas	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEL	186	tissue_specific	marker	body of pancreas, type B pancreatic cell, pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEL	1,233

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEL	P19835	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Digestion of dietary lipid	1	1631.4×	0.004	CEL
Digestion and absorption	1	761.3×	0.004	CEL
Digestion	1	571.0×	0.004	CEL
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.005	CEL
Developmental Cell Lineages	1	223.9×	0.005	CEL
Developmental Biology	1	14.5×	0.069	CEL

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
pancreatic juice secretion	1	3370.4×	8e-04	CEL
ceramide catabolic process	1	2407.4×	8e-04	CEL
intestinal cholesterol absorption	1	1404.3×	9e-04	CEL
lipid metabolic process	1	91.6×	0.011	CEL

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
CEL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CEL	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CEL	3.1.1.13	sterol esterase

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	1	CEL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CEL	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.