Mosaic trisomy 2

Summary

Mosaic trisomy 2 (MONDO:0015763) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		22	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001562	Oligohydramnios	Frequent (30-79%)
HP:0002194	Delayed gross motor development	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0011800	Midface retrusion	Frequent (30-79%)
HP:0100790	Hernia	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000268	Dolichocephaly	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0001177	Preaxial hand polydactyly	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002251	Aganglionic megacolon	Occasional (5-29%)
HP:0002414	Spina bifida	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002984	Hypoplasia of the radius	Occasional (5-29%)
HP:0003022	Hypoplasia of the ulna	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0033725	Thin corpus callosum	Occasional (5-29%)
HP:0045005	Neural tube defect	Occasional (5-29%)
HP:0410030	Cleft lip	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic trisomy 2
Mondo ID	MONDO:0015763
Orphanet	1723
SNOMED CT	764623009
UMLS	C4707010
MedGen	1631294
GARD	0005331
Is cancer (heuristic)	no

Also known as: Mosaic trisomy chromosome 2 · Mosaic trisomy type 2 · trisomy 2 mosaicism

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › autosomal anomaly › chromosome 2 disorder › mosaic trisomy 2

Related subtypes (4): partial deletion of chromosome 2, partial duplication of chromosome 2, ring chromosome 2, maternal uniparental disomy of chromosome 2

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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703543	GRCh37/hg19 2p25.3-q37.3(chr2:1-243199373)	SRD5A2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRD5A2	Orphanet:1331	Familial prostate cancer
SRD5A2	Orphanet:753	46,XY difference of sex development due to 5-alpha-reductase 2 deficiency

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
SRD5A2	HGNC:11285	ENSG00000277893	P31213	3-oxo-5-alpha-steroid 4-dehydrogenase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRD5A2	3-oxo-5-alpha-steroid 4-dehydrogenase 2	Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids.

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)
SRD5A2	Enzyme (other)	yes	1.3.1.22	3-oxo-5_a-steroid_4-DH_C, 3-oxo-5-alpha-steroid_4-DH, SRD5A/TECR

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
bronchial epithelial cell	1
corpus epididymis	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRD5A2	66	tissue_specific	marker	corpus epididymis, bronchial epithelial cell, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRD5A2	1,103

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRD5A2	P31213	1

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
Androgen biosynthesis	1	1038.2×	0.005	SRD5A2
Metabolism of steroid hormones	1	519.1×	0.005	SRD5A2
Metabolism of steroids	1	137.6×	0.012	SRD5A2
Metabolism of lipids	1	31.6×	0.040	SRD5A2
Metabolism	1	11.6×	0.086	SRD5A2

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
phthalate metabolic process	1	16852.0×	9e-04	SRD5A2
biphenyl metabolic process	1	8426.0×	9e-04	SRD5A2
dibenzo-p-dioxin metabolic process	1	8426.0×	9e-04	SRD5A2
response to biphenyl	1	5617.3×	1e-03	SRD5A2
response to follicle-stimulating hormone	1	4213.0×	0.001	SRD5A2
testosterone biosynthetic process	1	2808.7×	0.001	SRD5A2
steroid catabolic process	1	2407.4×	0.001	SRD5A2
female genitalia development	1	2407.4×	0.001	SRD5A2
androgen biosynthetic process	1	1872.4×	0.001	SRD5A2
hypothalamus development	1	1053.2×	0.002	SRD5A2
androgen metabolic process	1	887.0×	0.002	SRD5A2
male genitalia development	1	887.0×	0.002	SRD5A2
response to steroid hormone	1	842.6×	0.002	SRD5A2
response to testosterone	1	468.1×	0.003	SRD5A2
response to peptide hormone	1	391.9×	0.004	SRD5A2
response to nutrient levels	1	366.4×	0.004	SRD5A2
bone development	1	276.3×	0.005	SRD5A2
hippocampus development	1	230.8×	0.005	SRD5A2
male gonad development	1	156.0×	0.007	SRD5A2
cell-cell signaling	1	69.6×	0.015	SRD5A2
response to xenobiotic stimulus	1	69.1×	0.015	SRD5A2
cell differentiation	1	29.1×	0.034	SRD5A2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
SRD5A2	FINASTERIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRD5A2	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FINASTERIDE	4	SRD5A2
GAMOLENIC ACID	3	SRD5A2
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SRD5A2	119	Binding:115, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRD5A2	1.3.1.22, 1.3.99.5	3-oxo-5alpha-steroid 4-dehydrogenase (NADP+), 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SRD5A2	119

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

5 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)
FINASTERIDE	4	SRD5A2
GAMOLENIC ACID	3	SRD5A2
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SRD5A2
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.