Renal hypodysplasia/aplasia 4

disease

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Also known as RHDA4

Summary

Renal hypodysplasia/aplasia 4 (MONDO:0030822) is a disease caused by GFRA1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: GFRA1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal hypodysplasia/aplasia 4
Mondo ID	MONDO:0030822
OMIM	619887
UMLS	C5676993
MedGen	1808595
GARD	0025644
Is cancer (heuristic)	no

Also known as: renal hypodysplasia/aplasia 4 · RHDA4

Data availability: 5 ClinVar variants · 3 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 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686971	NM_005264.8(GFRA1):c.1294del (p.Thr432fs)	GFRA1	Pathogenic	no assertion criteria provided
1686972	NM_005264.8(GFRA1):c.628G>T (p.Gly210Ter)	GFRA1	Pathogenic	no assertion criteria provided
1686970	NM_005264.8(GFRA1):c.676C>T (p.Arg226Ter)	GFRA1	Likely pathogenic	criteria provided, single submitter
1705592	NM_005264.8(GFRA1):c.362A>G (p.Tyr121Cys)	GFRA1	Uncertain significance	criteria provided, single submitter
3393411	NM_005264.8(GFRA1):c.1024A>G (p.Ile342Val)	GFRA1	Uncertain significance	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
GFRA1	Strong	Autosomal recessive	renal hypodysplasia/aplasia 4	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GFRA1	Orphanet:1848	Renal agenesis, bilateral

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
GFRA1	HGNC:4243	ENSG00000151892	P56159	GDNF family receptor alpha-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GFRA1	GDNF family receptor alpha-1	Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GFRA1	Other/Unknown	no		GDNF_rcpt, GDNF_rcpt_A1, GDNF/GAS1

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
dorsal root ganglion	1
endometrium epithelium	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GFRA1	231	broad	marker	endometrium epithelium, trigeminal ganglion, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GFRA1	1,492

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GFRA1	P56159	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Formation of the ureteric bud	1	496.5×	0.005	GFRA1
RET signaling	1	259.6×	0.005	GFRA1
NCAM1 interactions	1	248.3×	0.005	GFRA1
RAF/MAP kinase cascade	1	61.1×	0.016	GFRA1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glial cell-derived neurotrophic factor receptor signaling pathway	1	1203.7×	0.006	GFRA1
male gonad development	1	156.0×	0.014	GFRA1
kidney development	1	140.4×	0.014	GFRA1
neuron projection development	1	122.1×	0.014	GFRA1
cell surface receptor signaling pathway	1	64.1×	0.019	GFRA1
cell migration	1	61.5×	0.019	GFRA1
nervous system development	1	45.9×	0.022	GFRA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GFRA1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GFRA1	2	Binding:2

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	1	GFRA1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GFRA1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: GFRA1