Short stature, Dauber-Argente type

Summary

Short stature, Dauber-Argente type (MONDO:0859182) is a disease caused by PAPPA2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PAPPA2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Short stature, Dauber-Argente type
Mondo ID	MONDO:0859182
OMIM	619489
UMLS	C5561968
MedGen	1794178
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › Short stature, Dauber-Argente type

Related subtypes (21): autoimmune disorder of musculoskeletal system, musculoskeletal system benign neoplasm, musculoskeletal system cancer, Klippel-Feil syndrome, enthesopathy, muscle tissue disorder, fasciitis, skeletal system disorder, synovial chondromatosis, auriculoosteodysplasia, hypertrophic osteoarthropathy, primary, autosomal dominant, Upington disease, Ramon syndrome, osteoporosis-oculocutaneous hypopigmentation syndrome, short stature, Brussels type, wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia, CINCA syndrome, chondrodysplasia with joint dislocations, gPAPP type, ligament disorder, synovium disorder, disease of the tendon

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

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1202641	NM_020318.3(PAPPA2):c.1928_1929insAT (p.Asp643fs)	PAPPA2	Pathogenic	no assertion criteria provided
1202642	NM_020318.3(PAPPA2):c.3098C>T (p.Ala1033Val)	PAPPA2	Pathogenic	no assertion criteria provided
1202643	NM_020318.3(PAPPA2):c.2656G>T (p.Glu886Ter)	PAPPA2	Pathogenic	no assertion criteria provided
4845794	NM_020318.3(PAPPA2):c.2958del (p.Leu987fs)	PAPPA2	Likely pathogenic	criteria provided, single submitter
2434576	NM_020318.3(PAPPA2):c.3798+10C>A	PAPPA2	Uncertain significance	criteria provided, single submitter
3065293	NM_020318.3(PAPPA2):c.2431+46del	PAPPA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
PAPPA2	Strong	Autosomal recessive	Short stature, Dauber-Argente type	3

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
PAPPA2	HGNC:14615	ENSG00000116183	Q9BXP8	Pappalysin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAPPA2	Pappalysin-2	Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the ‘163-Ser-|-Lys-164’ bond.

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)
PAPPA2	Protease	yes		Sushi_SCR_CCP_dom, Notch_dom, LamG-like

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
decidua	1
islet of Langerhans	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAPPA2	176	tissue_specific	marker	decidua, placenta, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAPPA2	699

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAPPA2	Q9BXP8	1

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 Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	PAPPA2

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
response to salt stress	1	1872.4×	0.003	PAPPA2
bone morphogenesis	1	601.9×	0.004	PAPPA2
regulation of cell growth	1	221.7×	0.008	PAPPA2
cell surface receptor signaling pathway	1	64.1×	0.020	PAPPA2
proteolysis	1	34.2×	0.029	PAPPA2

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
PAPPA2	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	1	PAPPA2
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)
PAPPA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.