Abdominal obesity-metabolic syndrome 4

Summary

Abdominal obesity-metabolic syndrome 4 (MONDO:0032837) 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	abdominal obesity-metabolic syndrome 4
Mondo ID	MONDO:0032837
OMIM	618620
DOID	DOID:0080945
UMLS	C5231430
MedGen	1704861
GARD	0025757
Is cancer (heuristic)	no

Also known as: AOMS4

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › abdominal obesity-metabolic syndrome › abdominal obesity-metabolic syndrome 4

Related subtypes (4): metabolic syndrome X, abdominal obesity-metabolic syndrome quantitative trait locus 2, abdominal obesity-metabolic syndrome 3, LIPE-related familial partial lipodystrophy

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:

3 uncertain significance, 3 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
633592	NM_033440.3(CELA2A):c.361G>A (p.Asp121Asn)	CELA2A	Pathogenic	no assertion criteria provided
633594	NM_033440.3(CELA2A):c.639+1G>C	CELA2A	Pathogenic	no assertion criteria provided
633595	NM_033440.3(CELA2A):c.209C>T (p.Thr70Met)	CELA2A	Pathogenic	criteria provided, multiple submitters, no conflicts
3385400	NM_033440.3(CELA2A):c.572G>A (p.Trp191Ter)	CELA2A	Likely pathogenic	criteria provided, single submitter
633593	NM_033440.3(CELA2A):c.253C>A (p.Leu85Met)	CELA2A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779043	NM_033440.3(CELA2A):c.442A>G (p.Ile148Val)	CELA2A	Uncertain significance	criteria provided, single submitter
3893041	NM_033440.3(CELA2A):c.356+5G>C	CELA2A	Uncertain significance	criteria provided, single submitter
4086226	NM_033440.3(CELA2A):c.379C>A (p.Leu127Met)	CELA2A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
CELA2A	Limited	Autosomal dominant	abdominal obesity-metabolic syndrome 4	2

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
CELA2A	HGNC:24609	ENSG00000142615	P08217	Chymotrypsin-like elastase family member 2A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CELA2A	Chymotrypsin-like elastase family member 2A	Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CELA2A	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA

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
islet of Langerhans	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CELA2A	128	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CELA2A	749

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CELA2A	P08217	93.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.011	CELA2A
Developmental Cell Lineages	1	223.9×	0.011	CELA2A
Formation of the cornified envelope	1	87.8×	0.019	CELA2A
Keratinization	1	55.7×	0.022	CELA2A
Developmental Biology	1	14.5×	0.069	CELA2A

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 catabolic process	1	4213.0×	0.001	CELA2A
regulation of platelet aggregation	1	2407.4×	0.001	CELA2A
regulation of insulin secretion	1	391.9×	0.004	CELA2A
response to insulin	1	230.8×	0.005	CELA2A
proteolysis	1	34.2×	0.029	CELA2A

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
CELA2A	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	1	CELA2A
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)
CELA2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.