Abdominal obesity-metabolic syndrome 3

Summary

Abdominal obesity-metabolic syndrome 3 (MONDO:0014352) is a disease caused by DYRK1B (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DYRK1B (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	abdominal obesity-metabolic syndrome 3
Mondo ID	MONDO:0014352
OMIM	615812
DOID	DOID:0060612
UMLS	C4014361
MedGen	862798
GARD	0024989
Is cancer (heuristic)	no

Also known as: abdominal obesity-metabolic syndrome 3 · abdominal obesity-metabolic syndrome type 3 · AOMS3 · DYRK1B metabolic syndrome · metabolic syndrome caused by mutation in DYRK1B

Data availability: 19 ClinVar variants · 4 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 3

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

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

19 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
496678	NM_001371928.1(AHDC1):c.2773C>T (p.Arg925Ter)	AHDC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132792	NM_004714.3(DYRK1B):c.304C>T (p.Arg102Cys)	DYRK1B	Pathogenic	criteria provided, single submitter
132793	NM_004714.3(DYRK1B):c.269A>C (p.His90Pro)	DYRK1B	Pathogenic	no assertion criteria provided
1803872	NM_004714.3(DYRK1B):c.63+7G>A	DYRK1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029888	NM_004714.3(DYRK1B):c.1541G>A (p.Arg514Gln)	DYRK1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285475	NM_004714.3(DYRK1B):c.1181C>T (p.Pro394Leu)	DYRK1B	Uncertain significance	criteria provided, single submitter
1803864	NM_004714.3(DYRK1B):c.1627C>T (p.Pro543Ser)	DYRK1B	Uncertain significance	criteria provided, single submitter
1803906	NM_004714.3(DYRK1B):c.1285G>C (p.Gly429Arg)	DYRK1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2343667	NM_004714.3(DYRK1B):c.532C>G (p.Arg178Gly)	DYRK1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441086	NM_004714.3(DYRK1B):c.1269G>T (p.Leu423=)	DYRK1B	Uncertain significance	criteria provided, single submitter
2441087	NM_004714.3(DYRK1B):c.1729C>T (p.Pro577Ser)	DYRK1B	Uncertain significance	criteria provided, single submitter
2584637	NM_004714.3(DYRK1B):c.1748C>T (p.Ala583Val)	DYRK1B	Uncertain significance	criteria provided, single submitter
2665009	NM_004714.3(DYRK1B):c.1640G>A (p.Arg547Gln)	DYRK1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064505	NM_004714.3(DYRK1B):c.1256G>T (p.Arg419Leu)	DYRK1B	Uncertain significance	criteria provided, single submitter
3242133	NM_004714.3(DYRK1B):c.1811C>T (p.Pro604Leu)	DYRK1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3353913	NM_004714.3(DYRK1B):c.236C>T (p.Ser79Leu)	DYRK1B	Uncertain significance	criteria provided, single submitter
3393112	NM_004714.3(DYRK1B):c.1228C>T (p.Arg410Cys)	DYRK1B	Uncertain significance	criteria provided, single submitter
3779301	NM_004714.3(DYRK1B):c.1640G>T (p.Arg547Leu)	DYRK1B	Uncertain significance	criteria provided, single submitter
4082207	NM_004714.3(DYRK1B):c.1120C>T (p.Arg374Trp)	DYRK1B	Uncertain significance	criteria provided, single submitter

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
DYRK1B	Strong	Autosomal dominant	abdominal obesity-metabolic syndrome 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AHDC1	Orphanet:412069	AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DYRK1B	HGNC:3092	ENSG00000105204	Q9Y463	Dual specificity tyrosine-phosphorylation-regulated kinase 1B	gencc,clinvar
AHDC1	HGNC:25230	ENSG00000126705	Q5TGY3	Transcription factor Gibbin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYRK1B	Dual specificity tyrosine-phosphorylation-regulated kinase 1B	Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities.
AHDC1	Transcription factor Gibbin	Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYRK1B	Kinase	yes	2.7.12.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
AHDC1	Other/Unknown	no		DUF4683, AHDC1

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
right testis	1
skeletal muscle tissue	1
Brodmann (1909) area 10	1
frontal pole	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYRK1B	134	ubiquitous	yes	hindlimb stylopod muscle, skeletal muscle tissue, right testis
AHDC1	232	ubiquitous	marker	paraflocculus, Brodmann (1909) area 10, frontal pole

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYRK1B	1,533
AHDC1	787

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYRK1B	Q9Y463	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AHDC1	Q5TGY3	38.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skin morphogenesis	1	702.2×	0.010	AHDC1
myoblast fusion	1	300.9×	0.010	DYRK1B
mesoderm formation	1	247.8×	0.010	AHDC1
adipose tissue development	1	200.6×	0.010	DYRK1B
protein phosphorylation	1	34.0×	0.041	DYRK1B
DNA repair	1	31.9×	0.041	DYRK1B
cell differentiation	1	14.6×	0.070	AHDC1
positive regulation of DNA-templated transcription	1	14.0×	0.070	DYRK1B

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
DYRK1B	NIRAPARIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DYRK1B	35	4
AHDC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIRAPARIB	4	DYRK1B
RUCAPARIB	4	DYRK1B
AFATINIB	4	DYRK1B
FEDRATINIB	4	DYRK1B
PALBOCICLIB	4	DYRK1B
ABEMACICLIB	4	DYRK1B
NINTEDANIB	4	DYRK1B
SUNITINIB	4	DYRK1B
MIDOSTAURIN	4	DYRK1B
CURCUMIN	3	DYRK1B
RIDAFOROLIMUS	3	DYRK1B
EPIGALOCATECHIN GALLATE	3	DYRK1B
ENZASTAURIN	3	DYRK1B
ALVOCIDIB	3	DYRK1B
LORECIVIVINT	3	DYRK1B
LESTAURTINIB	3	DYRK1B
RUBOXISTAURIN	3	DYRK1B
SILMITASERTIB	2	DYRK1B
SELICICLIB	2	DYRK1B
CC-401	2	DYRK1B
SU-014813	2	DYRK1B
CENISERTIB	2	DYRK1B
TG100-115	2	DYRK1B
RG-547	2	DYRK1B
AT-7519	2	DYRK1B
PICTILISIB	2	DYRK1B
PELITINIB	2	DYRK1B
SGX-523	1	DYRK1B
KW-2449	1	DYRK1B
AZD-1080	1	DYRK1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DYRK1B	422	Binding:412, Functional:5, ADMET:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DYRK1B	2.7.12.1	dual-specificity kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DYRK1B	422

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
NIRAPARIB	4	DYRK1B
RUCAPARIB	4	DYRK1B
AFATINIB	4	DYRK1B
FEDRATINIB	4	DYRK1B
PALBOCICLIB	4	DYRK1B
ABEMACICLIB	4	DYRK1B
NINTEDANIB	4	DYRK1B
SUNITINIB	4	DYRK1B
MIDOSTAURIN	4	DYRK1B
CURCUMIN	3	DYRK1B
RIDAFOROLIMUS	3	DYRK1B
EPIGALOCATECHIN GALLATE	3	DYRK1B
ENZASTAURIN	3	DYRK1B
ALVOCIDIB	3	DYRK1B
LORECIVIVINT	3	DYRK1B
LESTAURTINIB	3	DYRK1B
RUBOXISTAURIN	3	DYRK1B
SILMITASERTIB	2	DYRK1B
SELICICLIB	2	DYRK1B
CC-401	2	DYRK1B
SU-014813	2	DYRK1B
CENISERTIB	2	DYRK1B
TG100-115	2	DYRK1B
RG-547	2	DYRK1B
AT-7519	2	DYRK1B
PICTILISIB	2	DYRK1B
PELITINIB	2	DYRK1B
SGX-523	1	DYRK1B
KW-2449	1	DYRK1B
AZD-1080	1	DYRK1B

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DYRK1B
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	AHDC1

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)
AHDC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.