Renal hypodysplasia/aplasia 3

Summary

Renal hypodysplasia/aplasia 3 (MONDO:0024520) is a disease caused by GREB1L (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: GREB1L (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 79

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal hypodysplasia/aplasia 3
Mondo ID	MONDO:0024520
OMIM	617805
UMLS	C4540497
MedGen	1626497
GARD	0025410
Is cancer (heuristic)	no

Also known as: renal hypodysplasia/aplasia 3 · RHDA3

Data availability: 79 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › renal agenesis › renal hypodysplasia/aplasia 3

Related subtypes (5): renal hypodysplasia/aplasia 2, bilateral renal agenesis, renal agenesis, unilateral, renal hypodysplasia/aplasia 1, renal hypodysplasia/aplasia 4

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

79 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 22 likely pathogenic, 18 pathogenic, 5 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 benign, 1 likely pathogenic; association

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064690	NM_001142966.3(GREB1L):c.705G>T (p.Trp235Cys)	GREB1L	Pathogenic	no assertion criteria provided
1172553	NM_001142966.3(GREB1L):c.3977del (p.Lys1326fs)	GREB1L	Pathogenic	criteria provided, single submitter
1172554	NM_001142966.3(GREB1L):c.3983del (p.Gly1328fs)	GREB1L	Pathogenic	criteria provided, single submitter
2444520	NM_001142966.3(GREB1L):c.2614_2615del (p.Leu872fs)	GREB1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581335	NM_001142966.3(GREB1L):c.570dup (p.Phe191fs)	GREB1L	Pathogenic	criteria provided, single submitter
2626752	NM_001142966.3(GREB1L):c.1975C>T (p.Gln659Ter)	GREB1L	Pathogenic	criteria provided, single submitter
3894532	NM_001142966.3(GREB1L):c.2173C>T (p.Arg725Ter)	GREB1L	Pathogenic	criteria provided, single submitter
4291137	NM_001142966.3(GREB1L):c.2491_2492del (p.Leu831fs)	GREB1L	Pathogenic	criteria provided, single submitter
453273	NM_001142966.3(GREB1L):c.5378T>G (p.Leu1793Arg)	GREB1L	Pathogenic	criteria provided, single submitter
453274	NM_001142966.3(GREB1L):c.5608+1del	GREB1L	Pathogenic	no assertion criteria provided
453275	NM_001142966.3(GREB1L):c.4000dup (p.Leu1334fs)	GREB1L	Pathogenic	no assertion criteria provided
453276	NM_001142966.3(GREB1L):c.4680C>A (p.Tyr1560Ter)	GREB1L	Pathogenic	no assertion criteria provided
453277	NM_001142966.3(GREB1L):c.4700T>C (p.Leu1567Pro)	GREB1L	Pathogenic/Likely pathogenic	no assertion criteria provided
453279	NM_001142966.3(GREB1L):c.3295C>T (p.Gln1099Ter)	GREB1L	Pathogenic/Likely pathogenic	no assertion criteria provided
453280	NM_001142966.3(GREB1L):c.1582del (p.Gln528fs)	GREB1L	Pathogenic	no assertion criteria provided
453281	NM_001142966.3(GREB1L):c.4369-1G>C	GREB1L	Pathogenic	no assertion criteria provided
453282	NM_001142966.3(GREB1L):c.1780G>T (p.Glu594Ter)	GREB1L	Pathogenic	no assertion criteria provided
453283	NM_001142966.3(GREB1L):c.4607A>G (p.His1536Arg)	GREB1L	Pathogenic	no assertion criteria provided
4686791	NM_001142966.3(GREB1L):c.721C>T (p.Arg241Ter)	GREB1L	Pathogenic	criteria provided, multiple submitters, no conflicts
917901	NM_001142966.3(GREB1L):c.2787_2788del (p.Asp930fs)	GREB1L	Pathogenic	criteria provided, single submitter
917902	NM_001142966.3(GREB1L):c.2227del (p.Gln743fs)	GREB1L	Pathogenic	criteria provided, single submitter
2442169	NM_001142966.3(GREB1L):c.1984+3A>C	GREB1L	Likely pathogenic	criteria provided, single submitter
2498134	NM_001142966.3(GREB1L):c.4881_4882del (p.His1627fs)	GREB1L	Likely pathogenic	criteria provided, single submitter
2506468	NM_001142966.3(GREB1L):c.3704C>A (p.Ser1235Tyr)	GREB1L	Likely pathogenic	criteria provided, single submitter
2576970	NM_001142966.3(GREB1L):c.3863G>A (p.Trp1288Ter)	GREB1L	Likely pathogenic	criteria provided, single submitter
3066333	NM_001142966.3(GREB1L):c.1147_1153del (p.Thr383fs)	GREB1L	Likely pathogenic	criteria provided, single submitter
3238846	NM_001142966.3(GREB1L):c.3849_3850del (p.Tyr1284fs)	GREB1L	Likely pathogenic	criteria provided, single submitter
3256661	NM_001142966.3(GREB1L):c.3907del (p.Asp1303fs)	GREB1L	Likely pathogenic	criteria provided, single submitter
3382612	NM_001142966.3(GREB1L):c.2621G>A (p.Trp874Ter)	GREB1L	Likely pathogenic	criteria provided, single submitter
3775424	NM_001142966.3(GREB1L):c.3984_3996del (p.Tyr1330fs)	GREB1L	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
GREB1L	Definitive	Autosomal dominant	renal hypodysplasia/aplasia 3	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GREB1L	Orphanet:1848	Renal agenesis, bilateral
GREB1L	Orphanet:93100	Renal agenesis, unilateral

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GREB1L	HGNC:31042	ENSG00000141449	Q9C091	GREB1-like protein	gencc,clinvar
GREB1L-AS1	HGNC:58310	ENSG00000265751		GREB1L antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GREB1L	GREB1-like protein	Plays a major role in early metanephros and genital development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GREB1L	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C
GREB1L-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	2
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GREB1L	184	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius
GREB1L-AS1	78		yes	gastrocnemius, muscle of leg, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GREB1L	637
GREB1L-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GREB1L	Q9C091	72.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
paramesonephric duct development	1	4213.0×	0.002	GREB1L
mesonephric duct development	1	3370.4×	0.002	GREB1L
cardiac ventricle development	1	2407.4×	0.002	GREB1L
male genitalia development	1	887.0×	0.002	GREB1L
uterus development	1	802.5×	0.002	GREB1L
embryonic heart tube development	1	766.0×	0.002	GREB1L
cardiac muscle cell differentiation	1	674.1×	0.002	GREB1L
retinoic acid receptor signaling pathway	1	648.1×	0.002	GREB1L
ribosome biogenesis	1	624.1×	0.002	GREB1L
metanephros development	1	510.7×	0.003	GREB1L
branching involved in ureteric bud morphogenesis	1	366.4×	0.003	GREB1L
morphogenesis of an epithelium	1	343.9×	0.003	GREB1L
outflow tract morphogenesis	1	306.4×	0.004	GREB1L
kidney development	1	140.4×	0.007	GREB1L

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GREB1L	0	0
GREB1L-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	2	GREB1L, GREB1L-AS1

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)
GREB1L	0	—
GREB1L-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.