Renal dysplasia

Summary

Renal dysplasia (MONDO:0019638) is a disease with 3 cohort genes.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 2
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000	43.5	Europe	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000003	Multicystic kidney dysplasia	Frequent (30-79%)
HP:0000009	Functional abnormality of the bladder	Frequent (30-79%)
HP:0000091	Abnormal renal tubule morphology	Frequent (30-79%)
HP:0008678	Renal hypoplasia/aplasia	Frequent (30-79%)
HP:0011130	Abnormal renal calyx morphology	Frequent (30-79%)
HP:0012575	Abnormal nephron morphology	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0000010	Recurrent urinary tract infections	Occasional (5-29%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000070	Ureterocele	Occasional (5-29%)
HP:0000072	Hydroureter	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000105	Enlarged kidney	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001562	Oligohydramnios	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0004722	Thickening of the glomerular basement membrane	Occasional (5-29%)
HP:0005999	Ureteral atresia	Occasional (5-29%)
HP:0012300	Ureteral agenesis	Occasional (5-29%)
HP:0012330	Pyelonephritis	Occasional (5-29%)
HP:0012596	Moderate proteinuria	Occasional (5-29%)
HP:0030157	Flank pain	Occasional (5-29%)
HP:0031500	Abdominal mass	Occasional (5-29%)
HP:0031501	Pelvic mass	Occasional (5-29%)
HP:0001586	Vesicovaginal fistula	Very rare (<1-4%)
HP:0010957	Congenital posterior urethral valve	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	renal dysplasia
Mondo ID	MONDO:0019638
Orphanet	93108
ICD-10-CM	Q61.4
ICD-11	921320354
UMLS	C3536714
MedGen	760690
GARD	0019173
Is cancer (heuristic)	no

Also known as: renal dysplasia · renal dysplasia (disease)

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal dysplasia

Related subtypes (56): renal hypertension, kidney failure, nephritis, impaired renal function disease, nephrocalcinosis, atheroembolism of kidney, renal artery disease, nephrosis, cystic kidney disease, anuria, stricture or kinking of ureter, proteinuria, renal infectious disease, diabetes insipidus, orthostatic proteinuria, kidney hypertrophy, chronic kidney disease, hydronephrosis, renal tubular transport disease, kidney cortex necrosis, kidney papillary necrosis, perinephritis, renal aminoaciduria, autosomal dominant progressive nephropathy with hypertension, nephrolithiasis, X-linked diffuse leiomyomatosis-Alport syndrome, tubulointerstitial nephritis and uveitis syndrome, distal renal tubular acidosis, oligomeganephronia, duplication of urethra, renal tubular dysgenesis, exstrophy-epispadias complex, fetal lower urinary tract obstruction, IgG4-related kidney disease, congenital primary megaureter, renal nutcracker syndrome, renal hypoplasia, congenital megacalycosis, glomerular disorder, congenital renal artery stenosis, kidney neoplasm, renal tubule disorder, pyonephrosis, Arnold stickler bourne syndrome, C1q nephropathy, hypertensive nephropathy, atypical Fanconi syndrome-neonatal hyperinsulinism syndrome, idiopathic non-lupus full-house nephropathy, lachiewicz sibley syndrome, crush syndrome, obstructive nephropathy, inherited kidney disorder, acute tubulointerstitial nephritis, kidney cortex disease, non-syndromic supernumerary kidneys, neonatal renal venous thrombosis

Subtypes (2): renal dysplasia, unilateral, renal dysplasia, bilateral

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

2 retrieved; paginated sample, class counts are floors:

2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344867	NM_003396.3(WNT9B):c.11dup (p.Pro5fs)	LRRC37A2	Likely pathogenic	no assertion criteria provided
1804004	NM_001395002.1(MAP4K4):c.3458_3459del (p.Val1153fs)	MAP4K4	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
UPK3A	Supportive	Autosomal dominant	renal agenesis, unilateral	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UPK3A	Orphanet:93100	Renal agenesis, unilateral

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UPK3A	HGNC:12580	ENSG00000100373	O75631	Uroplakin-3a	gencc
LRRC37A2	HGNC:32404	ENSG00000238083	A6NM11	Leucine-rich repeat-containing protein 37A2	clinvar
MAP4K4	HGNC:6866	ENSG00000071054	O95819	Mitogen-activated protein kinase kinase kinase kinase 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UPK3A	Uroplakin-3a	Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells.
MAP4K4	Mitogen-activated protein kinase kinase kinase kinase 4	Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UPK3A	Other/Unknown	no		Uroplakin-3a, Uroplakin-3
LRRC37A2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37
MAP4K4	Kinase	yes		Prot_kinase_dom, CNH_dom, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

2 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
mucosa of urinary bladder	1
muscle of leg	1
cerebellar hemisphere	1
right testis	1
right uterine tube	1
C1 segment of cervical spinal cord	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UPK3A	126	broad	marker	gastrocnemius, mucosa of urinary bladder, muscle of leg
LRRC37A2	134		yes	right uterine tube, right testis, cerebellar hemisphere
MAP4K4	295	ubiquitous	marker	C1 segment of cervical spinal cord, cortical plate, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP4K4	1,975
LRRC37A2	601
UPK3A	508

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAP4K4	O95819	18

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UPK3A	O75631	78.77
LRRC37A2	A6NM11	42.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 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
Cellular Senescence	1	137.6×	0.022	MAP4K4
Oxidative Stress Induced Senescence	1	90.6×	0.022	MAP4K4
Cellular responses to stress	1	36.8×	0.032	MAP4K4
Cellular responses to stimuli	1	31.5×	0.032	MAP4K4

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
positive regulation of ARF protein signal transduction	1	2808.7×	0.003	MAP4K4
urea transport	1	2106.5×	0.003	UPK3A
urinary bladder development	1	2106.5×	0.003	UPK3A
positive regulation of focal adhesion disassembly	1	936.2×	0.005	MAP4K4
positive regulation of keratinocyte migration	1	648.1×	0.005	MAP4K4
positive regulation of hippo signaling	1	526.6×	0.005	MAP4K4
water transport	1	495.6×	0.005	UPK3A
sodium ion homeostasis	1	468.1×	0.005	UPK3A
negative regulation of cell-matrix adhesion	1	443.5×	0.005	MAP4K4
regulation of JNK cascade	1	443.5×	0.005	MAP4K4
potassium ion homeostasis	1	383.0×	0.005	UPK3A
positive regulation of focal adhesion assembly	1	324.1×	0.006	MAP4K4
regulation of MAPK cascade	1	227.7×	0.007	MAP4K4
neuron projection morphogenesis	1	138.1×	0.011	MAP4K4
epithelial cell differentiation	1	87.8×	0.017	UPK3A
cell morphogenesis	1	78.8×	0.017	UPK3A
MAPK cascade	1	76.6×	0.017	MAP4K4
kidney development	1	70.2×	0.017	UPK3A
protein phosphorylation	1	34.0×	0.034	MAP4K4
positive regulation of cell migration	1	30.9×	0.035	MAP4K4
intracellular signal transduction	1	19.1×	0.054	MAP4K4
negative regulation of apoptotic process	1	17.4×	0.057	MAP4K4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
MAP4K4	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAP4K4	62	4
UPK3A	0	0
LRRC37A2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	MAP4K4
AXITINIB	4	MAP4K4
SORAFENIB	4	MAP4K4
NERATINIB	4	MAP4K4
PALBOCICLIB	4	MAP4K4
ENTRECTINIB	4	MAP4K4
PACRITINIB	4	MAP4K4
VANDETANIB	4	MAP4K4
BOSUTINIB	4	MAP4K4
ABEMACICLIB	4	MAP4K4
GILTERITINIB	4	MAP4K4
PAZOPANIB	4	MAP4K4
NINTEDANIB	4	MAP4K4
SUNITINIB	4	MAP4K4
DASATINIB	4	MAP4K4
QUIZARTINIB	4	MAP4K4
MIDOSTAURIN	4	MAP4K4
GEFITINIB	4	MAP4K4
CRENOLANIB	3	MAP4K4
SARACATINIB	3	MAP4K4
BRIVANIB ALANINATE	3	MAP4K4
TESEVATINIB	3	MAP4K4
BRIVANIB	3	MAP4K4
FASUDIL	3	MAP4K4
CEDIRANIB	3	MAP4K4
DOVITINIB	3	MAP4K4
MOTESANIB	3	MAP4K4
LESTAURTINIB	3	MAP4K4
DORAMAPIMOD	2	MAP4K4
FORETINIB	2	MAP4K4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAP4K4	407	Binding:400, ADMET:5, Functional:1, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MAP4K4	407

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
PONATINIB	4	MAP4K4
AXITINIB	4	MAP4K4
SORAFENIB	4	MAP4K4
NERATINIB	4	MAP4K4
PALBOCICLIB	4	MAP4K4
ENTRECTINIB	4	MAP4K4
PACRITINIB	4	MAP4K4
VANDETANIB	4	MAP4K4
BOSUTINIB	4	MAP4K4
ABEMACICLIB	4	MAP4K4
GILTERITINIB	4	MAP4K4
PAZOPANIB	4	MAP4K4
NINTEDANIB	4	MAP4K4
SUNITINIB	4	MAP4K4
DASATINIB	4	MAP4K4
QUIZARTINIB	4	MAP4K4
MIDOSTAURIN	4	MAP4K4
GEFITINIB	4	MAP4K4
CRENOLANIB	3	MAP4K4
SARACATINIB	3	MAP4K4
BRIVANIB ALANINATE	3	MAP4K4
TESEVATINIB	3	MAP4K4
BRIVANIB	3	MAP4K4
FASUDIL	3	MAP4K4
CEDIRANIB	3	MAP4K4
DOVITINIB	3	MAP4K4
MOTESANIB	3	MAP4K4
LESTAURTINIB	3	MAP4K4
DORAMAPIMOD	2	MAP4K4
FORETINIB	2	MAP4K4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAP4K4
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	2	UPK3A, LRRC37A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UPK3A	0	—
LRRC37A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.