Late-onset nephronophthisis

Summary

Late-onset nephronophthisis (MONDO:0019742) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	late-onset nephronophthisis
Mondo ID	MONDO:0019742
Orphanet	93589
UMLS	C5681620
MedGen	1842314
GARD	0016824
Is cancer (heuristic)	no

Data availability: 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › nephronophthisis › late-onset nephronophthisis

Related subtypes (17): nephronophthisis 1, nephronophthisis 2, nephronophthisis 3, nephronophthisis 4, nephronophthisis 7, nephronophthisis-like nephropathy 1, nephronophthisis 11, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 19, nephronophthisis 20, nephronophthisis-like nephropathy 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 8 · 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
MAPKBP1	Definitive	Autosomal recessive	nephronophthisis 20	5
NPHP3	Definitive	Autosomal recessive	nephronophthisis	10
XPNPEP3	Strong	Autosomal recessive	nephronophthisis-like nephropathy 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XPNPEP3	Orphanet:93589	Late-onset nephronophthisis
MAPKBP1	Orphanet:93589	Late-onset nephronophthisis
MAPKBP1	Orphanet:93592	Juvenile nephronophthisis
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, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
XPNPEP3	HGNC:28052	ENSG00000196236	Q9NQH7	Xaa-Pro aminopeptidase 3	gencc
MAPKBP1	HGNC:29536	ENSG00000137802	O60336	Mitogen-activated protein kinase-binding protein 1	gencc
NPHP3	HGNC:7907	ENSG00000113971	Q7Z494	Nephrocystin-3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XPNPEP3	Xaa-Pro aminopeptidase 3	Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala.
MAPKBP1	Mitogen-activated protein kinase-binding protein 1	Negative regulator of NOD2 function.
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · 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
Protease	1	12.2×	0.239
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
XPNPEP3	Protease	yes	3.4.11.9	Pept_M24, Aminopep_P_N, Creatin/AminoP/Spt16_N
MAPKBP1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
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
bronchial epithelial cell	1
buccal mucosa cell	1
sperm	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	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
XPNPEP3	263	ubiquitous	marker	buccal mucosa cell, bronchial epithelial cell, sperm
MAPKBP1	251	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
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
XPNPEP3	2,395
NPHP3	2,275
MAPKBP1	1,056

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XPNPEP3	Q9NQH7	1
NPHP3	Q7Z494	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAPKBP1	O60336	62.82

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 3 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	5617.3×	0.003	NPHP3
determination of stomach left/right asymmetry	1	5617.3×	0.003	NPHP3
convergent extension involved in gastrulation	1	2808.7×	0.003	NPHP3
convergent extension	1	1872.4×	0.003	NPHP3
negative regulation of defense response to bacterium	1	1872.4×	0.003	MAPKBP1
determination of pancreatic left/right asymmetry	1	1123.5×	0.003	NPHP3
maintenance of animal organ identity	1	1123.5×	0.003	NPHP3
regulation of Wnt signaling pathway, planar cell polarity pathway	1	1123.5×	0.003	NPHP3
determination of liver left/right asymmetry	1	936.2×	0.003	NPHP3
ureter development	1	936.2×	0.003	NPHP3
atrial septum development	1	702.2×	0.004	NPHP3
kidney morphogenesis	1	624.1×	0.004	NPHP3
epithelial cilium movement involved in determination of left/right asymmetry	1	432.1×	0.006	NPHP3
negative regulation of interleukin-8 production	1	330.4×	0.007	MAPKBP1
glomerular filtration	1	312.1×	0.007	XPNPEP3
establishment or maintenance of cell polarity	1	133.8×	0.014	NPHP3
photoreceptor cell maintenance	1	119.5×	0.015	NPHP3
non-motile cilium assembly	1	96.8×	0.018	NPHP3
heart looping	1	89.2×	0.018	NPHP3
determination of left/right symmetry	1	85.1×	0.018	NPHP3
lung development	1	66.1×	0.022	NPHP3
negative regulation of canonical NF-kappaB signal transduction	1	57.3×	0.024	MAPKBP1
protein processing	1	56.7×	0.024	XPNPEP3
positive regulation of JNK cascade	1	54.5×	0.024	MAPKBP1
kidney development	1	46.8×	0.026	NPHP3
extracellular matrix organization	1	40.7×	0.029	NPHP3
negative regulation of canonical Wnt signaling pathway	1	39.3×	0.029	NPHP3
Wnt signaling pathway	1	33.2×	0.033	NPHP3
lipid metabolic process	1	30.5×	0.035	NPHP3
cilium assembly	1	24.5×	0.042	NPHP3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
XPNPEP3	0	0
MAPKBP1	0	0
NPHP3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
XPNPEP3	1	ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
XPNPEP3	3.4.11.9	Xaa-Pro aminopeptidase

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

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	1	XPNPEP3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	MAPKBP1, 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)
XPNPEP3	1	—
MAPKBP1	0	—
NPHP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.