Renal-hepatic-pancreatic dysplasia 1

Summary

Renal-hepatic-pancreatic dysplasia 1 (MONDO:0008833) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 386

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal-hepatic-pancreatic dysplasia 1
Mondo ID	MONDO:0008833
OMIM	208540
UMLS	C3715199
MedGen	811626
GARD	0018431
Is cancer (heuristic)	no

Also known as: NPHP3 renal-hepatic-pancreatic dysplasia · renal-hepatic-pancreatic dysplasia 1 · renal-hepatic-pancreatic dysplasia caused by mutation in NPHP3 · renal-hepatic-pancreatic dysplasia type 1 · RHPD1

Data availability: 386 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › renal-hepatic-pancreatic dysplasia › renal-hepatic-pancreatic dysplasia 1

Related subtypes (1): renal-hepatic-pancreatic dysplasia 2

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

386 retrieved; paginated sample, class counts are floors:

229 uncertain significance, 62 conflicting classifications of pathogenicity, 28 likely benign, 19 pathogenic/likely pathogenic, 17 likely pathogenic, 15 benign/likely benign, 12 pathogenic, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1706521	NM_153240.5(NPHP3):c.69del (p.Gly24fs)	LOC129937586	Pathogenic	no assertion criteria provided
1069581	NM_153240.5(NPHP3):c.3402_3403del (p.Ala1135fs)	NPHP3	Pathogenic	criteria provided, multiple submitters, no conflicts
1454636	NM_153240.5(NPHP3):c.469del (p.Arg157fs)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
195423	NM_153240.5(NPHP3):c.434_437del (p.Glu145fs)	NPHP3	Pathogenic	criteria provided, multiple submitters, no conflicts
2021418	NM_153240.5(NPHP3):c.1675del (p.His559fs)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
220868	NM_153240.5(NPHP3):c.2694-2_2694-1del	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2632	NM_153240.5(NPHP3):c.3821GAG[1] (p.Gly1275del)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2634	NM_153240.5(NPHP3):c.1381G>T (p.Glu461Ter)	NPHP3	Pathogenic	criteria provided, multiple submitters, no conflicts
2638	NM_153240.5(NPHP3):c.3340C>T (p.Gln1114Ter)	NPHP3	Pathogenic	criteria provided, single submitter
2640	NM_153240.5(NPHP3):c.2104C>T (p.Arg702Ter)	NPHP3	Pathogenic	criteria provided, multiple submitters, no conflicts
3383107	NM_153240.5(NPHP3):c.3357_3379dup (p.Leu1127delinsProTer)	NPHP3	Pathogenic	criteria provided, single submitter
462725	NM_153240.5(NPHP3):c.1985+1G>A	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
571434	NM_153240.5(NPHP3):c.2956dup (p.Gln986fs)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812666	NM_153240.5(NPHP3):c.520-1G>T	NPHP3	Pathogenic	criteria provided, multiple submitters, no conflicts
936828	NM_153240.5(NPHP3):c.2851C>T (p.Arg951Ter)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96511	NM_153240.5(NPHP3):c.2369T>C (p.Leu790Pro)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996537	NM_153240.5(NPHP3):c.2805C>T (p.Gly935=)	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029229	NM_153240.5(NPHP3):c.2570+1G>T	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454640	NM_153240.5(NPHP3):c.3775C>T (p.Arg1259Ter)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216136	NM_153240.5(NPHP3):c.1817G>A (p.Trp606Ter)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2634638	NM_153240.5(NPHP3):c.3812+2dup	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
499565	NM_153240.5(NPHP3):c.2311-2A>G	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
500889	NM_153240.5(NPHP3):c.634dup (p.Glu212fs)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
571559	NM_153240.5(NPHP3):c.2563C>T (p.Gln855Ter)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
597322	NM_153240.5(NPHP3):c.1101_1102insATTTTATTATT (p.His368fs)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635041	NM_153240.5(NPHP3):c.1174C>T (p.Arg392Ter)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
693989	NM_153240.5(NPHP3):c.3619C>T (p.Arg1207Ter)	NPHP3-ACAD11	Pathogenic	criteria provided, multiple submitters, no conflicts
848816	NM_153240.5(NPHP3):c.958-2A>G	NPHP3-ACAD11	Pathogenic	criteria provided, multiple submitters, no conflicts
853024	NM_153240.5(NPHP3):c.3003del (p.Phe1001fs)	NPHP3-ACAD11	Pathogenic	criteria provided, multiple submitters, no conflicts
96516	NM_153240.5(NPHP3):c.3373C>T (p.Arg1125Ter)	NPHP3-ACAD11	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NPHP3	Orphanet:294415	Renal-hepatic-pancreatic dysplasia
NPHP3	Orphanet:3032	NPHP3-related Meckel-like syndrome
NPHP3	Orphanet:3156	Senior-Loken syndrome
NPHP3	Orphanet:93589	Late-onset nephronophthisis
NPHP3	Orphanet:93591	Infantile nephronophthisis

Cohort genes → proteins

3 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NPHP3-AS1	HGNC:24129	ENSG00000248724		NPHP3 antisense RNA 1	clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar
NPHP3	HGNC:7907	ENSG00000113971	Q7Z494	Nephrocystin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NPHP3-AS1	Other/Unknown	no
NPHP3-ACAD11	Other/Unknown	no
NPHP3	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, P-loop_NTPase

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
male germ line stem cell (sensu Vertebrata) in testis	2
secondary oocyte	1
sural nerve	1
calcaneal tendon	1
endometrium	1
layer of synovial tissue	1
left ovary	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPHP3-AS1	59		marker	sural nerve, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
NPHP3-ACAD11	133	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, endometrium
NPHP3	254	ubiquitous	marker	superficial temporal artery, layer of synovial tissue, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NPHP3	2,275
NPHP3-AS1	0
NPHP3-ACAD11	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NPHP3	Q7Z494	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Trafficking of myristoylated proteins to the cilium	1	2284.0×	4e-04	NPHP3

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
determination of intestine left/right asymmetry	1	16852.0×	7e-04	NPHP3
determination of stomach left/right asymmetry	1	16852.0×	7e-04	NPHP3
convergent extension involved in gastrulation	1	8426.0×	9e-04	NPHP3
convergent extension	1	5617.3×	9e-04	NPHP3
determination of pancreatic left/right asymmetry	1	3370.4×	9e-04	NPHP3
maintenance of animal organ identity	1	3370.4×	9e-04	NPHP3
regulation of Wnt signaling pathway, planar cell polarity pathway	1	3370.4×	9e-04	NPHP3
determination of liver left/right asymmetry	1	2808.7×	9e-04	NPHP3
ureter development	1	2808.7×	9e-04	NPHP3
atrial septum development	1	2106.5×	0.001	NPHP3
kidney morphogenesis	1	1872.4×	0.001	NPHP3
epithelial cilium movement involved in determination of left/right asymmetry	1	1296.3×	0.002	NPHP3
establishment or maintenance of cell polarity	1	401.2×	0.005	NPHP3
photoreceptor cell maintenance	1	358.6×	0.005	NPHP3
non-motile cilium assembly	1	290.6×	0.006	NPHP3
heart looping	1	267.5×	0.006	NPHP3
determination of left/right symmetry	1	255.3×	0.006	NPHP3
lung development	1	198.3×	0.007	NPHP3
kidney development	1	140.4×	0.009	NPHP3
extracellular matrix organization	1	122.1×	0.010	NPHP3
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.010	NPHP3
Wnt signaling pathway	1	99.7×	0.011	NPHP3
lipid metabolic process	1	91.6×	0.011	NPHP3
cilium assembly	1	73.6×	0.014	NPHP3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
NPHP3-AS1	0	0
NPHP3-ACAD11	0	0
NPHP3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	3	NPHP3-AS1, NPHP3-ACAD11, NPHP3

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)
NPHP3-AS1	0	—
NPHP3-ACAD11	0	—
NPHP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.