Renal hypoplasia

Summary

Renal hypoplasia (MONDO:0019637) is a disease with 7 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 7
• ClinVar variants: 8
• 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:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000091	Abnormal renal tubule morphology	Frequent (30-79%)
HP:0005563	Decreased numbers of nephrons	Frequent (30-79%)
HP:0011035	Abnormal renal cortex morphology	Frequent (30-79%)
HP:0012210	Abnormal renal morphology	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0030162	Glomerulomegaly	Frequent (30-79%)
HP:0000010	Recurrent urinary tract infections	Occasional (5-29%)
HP:0000069	Abnormality of the ureter	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000122	Unilateral renal agenesis	Occasional (5-29%)
HP:0000125	Pelvic kidney	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001518	Small for gestational age	Occasional (5-29%)
HP:0001622	Premature birth	Occasional (5-29%)
HP:0001944	Dehydration	Occasional (5-29%)
HP:0001959	Polydipsia	Occasional (5-29%)
HP:0010481	Urethral valve	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	renal hypoplasia
Mondo ID	MONDO:0019637
Orphanet	93101
DOID	DOID:0080204
SNOMED CT	32659003
UMLS	C0266295
MedGen	120571
GARD	0019172
MedDRA	10049102
Is cancer (heuristic)	no

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

Data availability: 8 ClinVar variants · 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 hypoplasia

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 dysplasia, 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 hypoplasia, unilateral, renal hypoplasia, 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

8 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523434	NM_019023.5(PRMT7):c.1713C>A (p.Cys571Ter)	PRMT7	Pathogenic	criteria provided, multiple submitters, no conflicts
523435	NM_019023.5(PRMT7):c.322G>T (p.Glu108Ter)	PRMT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047903	GRCh37/hg19 4p16.3(chr4:388344-3872380)	TMEM175	Pathogenic	criteria provided, single submitter
523499	NM_012330.4(KAT6B):c.3399_3402del (p.Arg1133fs)	KAT6B	Likely pathogenic	criteria provided, single submitter
1344867	NM_003396.3(WNT9B):c.11dup (p.Pro5fs)	LRRC37A2	Likely pathogenic	no assertion criteria provided
1328399	NM_000278.5(PAX2):c.576del (p.Ile193fs)	PAX2	Likely pathogenic	criteria provided, single submitter
691939	NM_024072.4(DDX54):c.856G>A (p.Val286Met)	DDX54	Conflicting classifications of pathogenicity	no assertion criteria provided
242914	NM_000503.6(EYA1):c.121G>C (p.Glu41Gln)	EYA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
PRMT7	Orphanet:464288	Short stature-brachydactyly-obesity-global developmental delay syndrome
EYA1	Orphanet:107	BOR syndrome
EYA1	Orphanet:2792	Otofaciocervical syndrome
EYA1	Orphanet:52429	Branchiootic syndrome
PAX2	Orphanet:1475	Renal coloboma syndrome
PAX2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PAX2	Orphanet:97362	Renal hypoplasia, bilateral

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
DDX54	HGNC:20084	ENSG00000123064	Q8TDD1	ATP-dependent RNA helicase DDX54	clinvar
PRMT7	HGNC:25557	ENSG00000132600	Q9NVM4	Protein arginine N-methyltransferase 7	clinvar
TMEM175	HGNC:28709	ENSG00000127419	Q9BSA9	Endosomal/lysosomal proton channel TMEM175	clinvar
LRRC37A2	HGNC:32404	ENSG00000238083	A6NM11	Leucine-rich repeat-containing protein 37A2	clinvar
EYA1	HGNC:3519	ENSG00000104313	Q99502	Protein phosphatase EYA1	clinvar
PAX2	HGNC:8616	ENSG00000075891	Q02962	Paired box protein Pax-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
DDX54	ATP-dependent RNA helicase DDX54	Nucleolar RNA helicase that is involved in diverse cellular processes including ribosome biogenesis, DNA damage response, RNA splicing, transcriptional regulation, innate immunity, and nervous system development.
PRMT7	Protein arginine N-methyltransferase 7	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA.
TMEM175	Endosomal/lysosomal proton channel TMEM175	Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH.
EYA1	Protein phosphatase EYA1	Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5.
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.14

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
Transcription factor	2	2.4×	0.613
Enzyme (other)	1	1.7×	0.626
Other/Unknown	4	1.0×	0.626

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
DDX54	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
PRMT7	Enzyme (other)	yes	2.1.1.321	MeTrfase_PRMT7, Arg_MeTrfase, SAM-dependent_MTases_sf
TMEM175	Other/Unknown	no		TMEM175-like
LRRC37A2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37
EYA1	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

Expression context

Cohort genes with no expression data: 0.

5 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	3
sural nerve	2
cerebellar cortex	2
right hemisphere of cerebellum	2
cortical plate	1
ventricular zone	1
nucleus accumbens	1
upper arm skin	1
right testis	1
right uterine tube	1
choroid plexus epithelium	1
mucosa of paranasal sinus	1
urethra	1
adult mammalian kidney	1
metanephros cortex	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
DDX54	257	ubiquitous	marker	sural nerve, nucleus accumbens, upper arm skin
PRMT7	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
TMEM175	223	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
LRRC37A2	134		yes	right uterine tube, right testis, cerebellar hemisphere
EYA1	205	broad	marker	choroid plexus epithelium, urethra, mucosa of paranasal sinus
PAX2	92	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX54	4,447
KAT6B	2,214
PAX2	2,208
PRMT7	2,036
EYA1	1,806
LRRC37A2	601
TMEM175	548

Intra-cohort edges

A	B	Sources
EYA1	PAX2	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TMEM175	Q9BSA9	18
DDX54	Q8TDD1	6
KAT6B	Q8WYB5	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRMT7	Q9NVM4	93.19
EYA1	Q99502	66.68
PAX2	Q02962	61.52
LRRC37A2	A6NM11	42.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 7 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the ureteric bud	2	248.3×	2e-04	EYA1, PAX2
Chromatin organization	2	40.8×	0.003	KAT6B, PRMT7
Chromatin modifying enzymes	2	36.1×	0.003	KAT6B, PRMT7
Formation of intermediate mesoderm	1	356.9×	0.006	PAX2
Nephron development	1	219.6×	0.008	PAX2
Formation of the nephric duct	1	158.6×	0.009	PAX2
RMTs methylate histone arginines	1	36.6×	0.030	PRMT7
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	36.6×	0.030	EYA1
HATs acetylate histones	1	19.8×	0.049	KAT6B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesodermal cell fate specification	2	702.2×	3e-04	EYA1, PAX2
cochlea morphogenesis	2	193.7×	0.002	EYA1, PAX2
branching involved in ureteric bud morphogenesis	2	122.1×	0.004	EYA1, PAX2
optic chiasma development	1	2808.7×	0.005	PAX2
otic vesicle morphogenesis	1	2808.7×	0.005	EYA1
positive regulation of optic nerve formation	1	2808.7×	0.005	PAX2
optic cup morphogenesis involved in camera-type eye development	1	1404.3×	0.005	PAX2
optic nerve structural organization	1	1404.3×	0.005	PAX2
regulation of metanephros size	1	1404.3×	0.005	PAX2
pronephric field specification	1	1404.3×	0.005	PAX2
obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	1	1404.3×	0.005	PAX2
obsolete negative regulation of apoptotic process involved in metanephric collecting duct development	1	1404.3×	0.005	PAX2
obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development	1	1404.3×	0.005	PAX2
positive regulation of metanephric DCT cell differentiation	1	1404.3×	0.005	PAX2
positive regulation of epithelial cell proliferation	2	81.4×	0.005	EYA1, PAX2
nephric duct formation	1	936.2×	0.006	PAX2
positive regulation of metanephric glomerulus development	1	936.2×	0.006	PAX2
positive regulation of secondary heart field cardioblast proliferation	1	936.2×	0.006	EYA1
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	936.2×	0.006	PAX2
striated muscle tissue development	1	702.2×	0.006	EYA1
peptidyl-arginine methylation	1	702.2×	0.006	PRMT7
ureter maturation	1	702.2×	0.006	PAX2
metanephric distal convoluted tubule development	1	702.2×	0.006	PAX2
optic nerve morphogenesis	1	561.7×	0.006	PAX2
vestibulocochlear nerve formation	1	561.7×	0.006	PAX2
lysosomal lumen pH elevation	1	561.7×	0.006	TMEM175
metanephric mesenchymal cell differentiation	1	561.7×	0.006	PAX2
metanephric epithelium development	1	561.7×	0.006	PAX2
metanephric nephron tubule formation	1	561.7×	0.006	PAX2
regulation of metanephric nephron tubule epithelial cell differentiation	1	561.7×	0.006	PAX2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 3 of 7 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRMT7	1	3
KAT6B	0	0
DDX54	0	0
TMEM175	0	0
LRRC37A2	0	0
EYA1	0	0
PAX2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADEMETIONINE	3	PRMT7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PRMT7	100	Binding:98, Functional:2
KAT6B	22	Binding:20, Functional:2
PAX2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase
PRMT7	2.1.1.321	type III protein arginine methyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRMT7	100

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
ADEMETIONINE	3	PRMT7

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	1	PRMT7
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	KAT6B, DDX54, TMEM175, LRRC37A2, EYA1, PAX2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KAT6B	22	—
DDX54	0	—
TMEM175	0	—
LRRC37A2	0	—
EYA1	0	—
PAX2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.