Penoscrotal transposition

Summary

Penoscrotal transposition (MONDO:0017285) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 20

Clinical features

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000047	Hypospadias	Very frequent (80-99%)
HP:0000069	Abnormality of the ureter	Very frequent (80-99%)
HP:0000078	Abnormality of the genital system	Very frequent (80-99%)
HP:0000104	Renal agenesis	Very frequent (80-99%)
HP:0000110	Renal dysplasia	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000768	Pectus carinatum	Very frequent (80-99%)
HP:0000795	Abnormality of the urethra	Very frequent (80-99%)
HP:0000811	Abnormal external genitalia	Very frequent (80-99%)
HP:0001638	Cardiomyopathy	Very frequent (80-99%)
HP:0002120	Cerebral cortical atrophy	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0006610	Wide intermamillary distance	Very frequent (80-99%)
HP:0007598	Bilateral single transverse palmar creases	Very frequent (80-99%)
HP:0100600	Penoscrotal transposition	Very frequent (80-99%)
HP:0000049	Shawl scrotum	Frequent (30-79%)
HP:0000269	Prominent occiput	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0010751	Chin dimple	Frequent (30-79%)
HP:0006443	Patellar aplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	penoscrotal transposition
Mondo ID	MONDO:0017285
MeSH	C536650
Orphanet	2842
ICD-11	1417779551
NCIT	C99010
SNOMED CT	312005008
UMLS	C1868854
MedGen	357036
GARD	0004273
MedDRA	10067287
Is cancer (heuristic)	no

Also known as: congenital penoscrotal transposition · congenital transposition of the penis · penoscrotal transposition · penoscrotal transposition (disease) · Prepenile scrotum

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › penoscrotal transposition

Related subtypes (25): benign male reproductive system neoplasm, hematocele of tunica vaginalis testis, male genital organ stricture, male genital organ vascular disease, penile disorder, testicular disorder, prostate disorder, epididymitis, hydrocele, male infertility, male genital tuberculosis, spermatocele, dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome, cryptorchidism, diphallia, postorgasmic illness syndrome, congenital bilateral absence of vas deferens, posterior hypospadias, isolated micropenis, male reproductive system neoplasm, fournier gangrene, congenital agenesis of the scrotum, scrotal disorder, congenital megaprepuce, epididymis disease

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1339481	NM_002204.4(ITGA3):c.1766G>C (p.Arg589Pro)	ITGA3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA3	Orphanet:306504	Interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome

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
ITGA3	HGNC:6139	ENSG00000005884	P26006	Integrin alpha-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGA3	Integrin alpha-3	Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA3	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p

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
metanephric glomerulus	1
right coronary artery	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA3	149	ubiquitous	marker	metanephric glomerulus, right coronary artery, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA3	2,079

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITGA3	P26006	83.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
MET promotes cell motility	1	601.0×	0.007	ITGA3
Basigin interactions	1	439.2×	0.007	ITGA3
Laminin interactions	1	380.7×	0.007	ITGA3
MET activates PTK2 signaling	1	380.7×	0.007	ITGA3
Signaling by MET	1	317.2×	0.007	ITGA3
Integrin cell surface interactions	1	134.3×	0.014	ITGA3
Cell surface interactions at the vascular wall	1	95.2×	0.017	ITGA3
Extracellular matrix organization	1	63.1×	0.022	ITGA3
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.024	ITGA3
Hemostasis	1	36.0×	0.031	ITGA3
Signal Transduction	1	10.2×	0.098	ITGA3

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
negative regulation of cell projection organization	1	5617.3×	0.002	ITGA3
response to gonadotropin	1	5617.3×	0.002	ITGA3
renal filtration	1	5617.3×	0.002	ITGA3
nephron development	1	1872.4×	0.003	ITGA3
mesodermal cell differentiation	1	1532.0×	0.003	ITGA3
dendritic spine maintenance	1	1296.3×	0.003	ITGA3
regulation of BMP signaling pathway	1	1203.7×	0.003	ITGA3
maternal process involved in female pregnancy	1	936.2×	0.003	ITGA3
regulation of Wnt signaling pathway	1	887.0×	0.003	ITGA3
regulation of transforming growth factor beta receptor signaling pathway	1	802.5×	0.003	ITGA3
negative regulation of Rho protein signal transduction	1	766.0×	0.003	ITGA3
exploration behavior	1	648.1×	0.004	ITGA3
leukocyte migration	1	624.1×	0.004	ITGA3
synaptic membrane adhesion	1	581.1×	0.004	ITGA3
positive regulation of cell-substrate adhesion	1	495.6×	0.004	ITGA3
skin development	1	443.5×	0.004	ITGA3
positive regulation of epithelial cell migration	1	411.0×	0.004	ITGA3
positive regulation of protein localization to plasma membrane	1	271.8×	0.006	ITGA3
Rho protein signal transduction	1	247.8×	0.006	ITGA3
lung development	1	198.3×	0.007	ITGA3
memory	1	183.2×	0.008	ITGA3
cell-matrix adhesion	1	163.6×	0.008	ITGA3
integrin-mediated signaling pathway	1	160.5×	0.008	ITGA3
positive regulation of neuron projection development	1	137.0×	0.009	ITGA3
neuron migration	1	133.8×	0.009	ITGA3
cell-cell adhesion	1	101.5×	0.011	ITGA3
heart development	1	78.8×	0.014	ITGA3
response to xenobiotic stimulus	1	69.1×	0.015	ITGA3
positive regulation of gene expression	1	38.7×	0.026	ITGA3

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
ITGA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ITGA3	5	Binding:5

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	ITGA3
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)
ITGA3	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.