Urogenital tract malformation

Summary

Urogenital tract malformation (MONDO:0019356) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	urogenital tract malformation
Mondo ID	MONDO:0019356
Orphanet	83001
ICD-10-CM	Q60-Q64
UMLS	C0042063
MedGen	52948
GARD	0019029
Is cancer (heuristic)	no

Data availability: 16 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › urogenital tract malformation

Related subtypes (51): disorder of sexual differentiation, hereditary neurocutaneous angioma, nevoid basal cell carcinoma syndrome, angioosteohypertrophic syndrome, Larsen syndrome, schwannomatosis, linear nevus sebaceous syndrome, lethal Larsen-like syndrome, pseudodiastrophic dysplasia, focal dermal hypoplasia, microtia, neurofibromatosis-Noonan syndrome, Becker nevus syndrome, Legius syndrome, bone fragility with contractures, arterial rupture, and deafness, blindness - scoliosis - arachnodactyly syndrome, cutis laxa - Marfanoid syndrome, Maffucci syndrome, hydrops fetalis, ankyloblepharon filiforme-imperforate anus syndrome, developmental anomaly of metabolic origin, progeroid syndrome, facial cleft, Desbuquois dysplasia, cysts and fistulae of the face and oral cavity, macroglossia, middle ear anomaly, cleft palate, cutis laxa, infectious embryofetopathy, toxic or drug-related embryofetopathy, hemihyperplasia-multiple lipomatosis syndrome, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis, PTEN hamartoma tumor syndrome, marfanoid habitus-inguinal hernia-advanced bone age syndrome, neurofibromatosis type 1, multiple congenital anomalies/dysmorphic syndrome, congenital limb malformation, hereditary hemorrhagic telangiectasia, congenital anomaly of kidney and urinary tract, anotia, central nervous system malformation, Ehlers-Danlos syndrome, X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome, joint laxity, short stature, and myopia, diaphragmatic malformation, abdominal wall malformation, port-wine nevi-mega cisterna magna-hydrocephalus syndrome, conjoined twins, TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations

Subtypes (3): exstrophy-epispadias complex, fetal lower urinary tract obstruction, isolated persistent urogenital sinus

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

16 retrieved; paginated sample, class counts are floors:

7 likely pathogenic, 3 pathogenic, 3 pathogenic/likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1180850	NM_032551.5(KISS1R):c.969C>A (p.Tyr323Ter)	KISS1R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619228	NM_001127392.3(MYRF):c.1303G>A (p.Gly435Arg)	MYRF	Pathogenic/Likely pathogenic	no assertion criteria provided
1180650	NM_138694.4(PKHD1):c.8642+1G>T	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
189143	NM_138694.4(PKHD1):c.7916C>A (p.Ser2639Ter)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
371152	NM_138694.4(PKHD1):c.10972_10973del (p.Ile3658fs)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
3339	NM_000348.4(SRD5A2):c.164T>A (p.Leu55Gln)	SRD5A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180776	NM_001692.4(ATP6V1B1):c.509del (p.Pro170fs)	ATP6V1B1	Likely pathogenic	criteria provided, single submitter
977137	NM_001127392.3(MYRF):c.1786C>T (p.Gln596Ter)	MYRF	Likely pathogenic	criteria provided, single submitter
996605	NM_001127392.3(MYRF):c.1904-1G>A	MYRF	Likely pathogenic	no assertion criteria provided
996606	NM_001127392.3(MYRF):c.1160T>C (p.Phe387Ser)	MYRF	Likely pathogenic	no assertion criteria provided
996607	NM_001127392.3(MYRF):c.1209G>C (p.Gln403His)	MYRF	Likely pathogenic	no assertion criteria provided
996608	NM_001127392.3(MYRF):c.1435C>G (p.Leu479Val)	MYRF	Likely pathogenic	no assertion criteria provided
996740	NM_001127392.3(MYRF):c.239dup (p.Gly81fs)	MYRF	Likely pathogenic	no assertion criteria provided
996604	NM_001127392.3(MYRF):c.2036T>C (p.Val679Ala)	MYRF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267945	46;XY;t(1;18)(q32.1;q22.1)		Uncertain significance	criteria provided, single submitter
619229	NM_001127392.3(MYRF):c.2084G>A (p.Arg695His)	MYRF	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · 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
MYRF	Orphanet:647811	Cardiac-urogenital syndrome
KISS1R	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
KISS1R	Orphanet:650077	Genetic central precocious puberty in female
KISS1R	Orphanet:650097	Genetic central precocious puberty in male
ATP6V1B1	Orphanet:402041	Autosomal recessive distal renal tubular acidosis
PKHD1	Orphanet:53035	Caroli disease
PKHD1	Orphanet:731	Autosomal recessive polycystic kidney disease

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SRD5A2	HGNC:11285	ENSG00000277893	P31213	3-oxo-5-alpha-steroid 4-dehydrogenase 2	clinvar
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	clinvar
KISS1R	HGNC:4510	ENSG00000116014	Q969F8	KiSS-1 receptor	clinvar
ATP6V1B1	HGNC:853	ENSG00000116039	P15313	V-type proton ATPase subunit B, kidney isoform	clinvar
PKHD1	HGNC:9016	ENSG00000170927	P08F94	Fibrocystin	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.
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
KISS1R	KiSS-1 receptor	Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54).
ATP6V1B1	V-type proton ATPase subunit B, kidney isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
PKHD1	Fibrocystin	Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/ or ensures the maintenance of the architecture of the lumen of the kidney.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.6

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	5.8×	0.480
GPCR	1	4.8×	0.480
Enzyme (other)	1	2.4×	0.588
Transcription factor	1	1.6×	0.595
Other/Unknown	1	0.4×	0.983

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
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
KISS1R	GPCR	yes		GPCR_Rhodpsn, KiSS_1_rcpt, GPCR_Rhodpsn_7TM
ATP6V1B1	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu
PKHD1	Antibody/Immunoglobulin	yes		IPT_dom, PbH1, Pectin_lyase_fold/virulence

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	2
bronchial epithelial cell	1
corpus epididymis	1
epithelium of bronchus	1
C1 segment of cervical spinal cord	1
inferior vagus X ganglion	1
middle frontal gyrus	1
buccal mucosa cell	1
endothelial cell	1
pons	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
kidney epithelium	1
renal medulla	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
MYRF	223	ubiquitous	marker	middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion
KISS1R	109	broad	yes	pons, buccal mucosa cell, endothelial cell
ATP6V1B1	152	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, metanephros cortex
PKHD1	51	tissue_specific	marker	kidney epithelium, renal medulla, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V1B1	2,172
PKHD1	1,211
SRD5A2	1,103
MYRF	979
KISS1R	811

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KISS1R	Q969F8	6
MYRF	Q9Y2G1	2
SRD5A2	P31213	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP6V1B1	P15313	87.21
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 5 evidence-associated genes (3 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 3 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	346.1×	0.030	SRD5A2
Metabolism of steroid hormones	1	173.0×	0.030	SRD5A2
Insulin receptor recycling	1	126.9×	0.030	ATP6V1B1
Transferrin endocytosis and recycling	1	122.8×	0.030	ATP6V1B1
ROS and RNS production in phagocytes	1	112.0×	0.030	ATP6V1B1
Amino acids regulate mTORC1	1	66.8×	0.042	ATP6V1B1
Metabolism of steroids	1	45.9×	0.053	SRD5A2
Ion channel transport	1	32.0×	0.066	ATP6V1B1
Class A/1 (Rhodopsin-like receptors)	1	24.7×	0.068	KISS1R
Peptide ligand-binding receptors	1	24.7×	0.068	KISS1R
GPCR ligand binding	1	21.4×	0.071	KISS1R
G alpha (q) signalling events	1	19.1×	0.073	KISS1R
GPCR downstream signalling	1	14.5×	0.088	KISS1R
Signaling by GPCR	1	13.4×	0.089	KISS1R
Metabolism of lipids	1	10.5×	0.104	SRD5A2
Metabolism	1	3.9×	0.251	SRD5A2
Signal Transduction	1	3.4×	0.267	KISS1R

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	3370.4×	0.011	SRD5A2
regulation of cholangiocyte proliferation	1	3370.4×	0.011	PKHD1
biphenyl metabolic process	1	1685.2×	0.011	SRD5A2
dibenzo-p-dioxin metabolic process	1	1685.2×	0.011	SRD5A2
renal tubular secretion	1	1123.5×	0.011	ATP6V1B1
response to biphenyl	1	1123.5×	0.011	SRD5A2
renal sodium ion transport	1	842.6×	0.011	ATP6V1B1
response to follicle-stimulating hormone	1	842.6×	0.011	SRD5A2
renal sodium excretion	1	842.6×	0.011	ATP6V1B1
central nervous system myelin maintenance	1	561.7×	0.011	MYRF
testosterone biosynthetic process	1	561.7×	0.011	SRD5A2
vacuolar proton-transporting V-type ATPase complex assembly	1	561.7×	0.011	ATP6V1B1
regulation of establishment of planar polarity	1	561.7×	0.011	PKHD1
steroid catabolic process	1	481.5×	0.011	SRD5A2
female genitalia development	1	481.5×	0.011	SRD5A2
pH reduction	1	481.5×	0.011	ATP6V1B1
androgen biosynthetic process	1	374.5×	0.011	SRD5A2
olfactory behavior	1	374.5×	0.011	ATP6V1B1
homeostatic process	1	337.0×	0.011	PKHD1
positive regulation of hormone secretion	1	337.0×	0.011	KISS1R
establishment of centrosome localization	1	337.0×	0.011	PKHD1
chloride ion homeostasis	1	306.4×	0.012	ATP6V1B1
regulation of pH	1	280.9×	0.013	ATP6V1B1
regulation of cell-matrix adhesion	1	259.3×	0.013	PKHD1
regulation of cell-cell adhesion	1	240.7×	0.013	PKHD1
negative regulation of epithelial cell apoptotic process	1	240.7×	0.013	PKHD1
hypothalamus development	1	210.7×	0.013	SRD5A2
central nervous system myelination	1	198.3×	0.013	MYRF
epithelial cell morphogenesis	1	187.2×	0.013	PKHD1
regulation of TOR signaling	1	187.2×	0.013	PKHD1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 3

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
KISS1R	3	3
MYRF	0	0
ATP6V1B1	0	0
PKHD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FINASTERIDE	4	SRD5A2
GAMOLENIC ACID	3	SRD5A2
KISSPEPTIN-10	3	KISS1R
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2
BENZETHONIUM CHLORIDE	2	KISS1R
TAK-448	2	KISS1R

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
KISS1R	48	Binding:24, Functional:24
ATP6V1B1	1	Binding:1

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: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

8 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
KISSPEPTIN-10	3	KISS1R
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2
BENZETHONIUM CHLORIDE	2	KISS1R
TAK-448	2	KISS1R

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	1	KISS1R
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	PKHD1
E	Difficult family or no structure, no drug	2	MYRF, ATP6V1B1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYRF	0	—
ATP6V1B1	1	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.