Nephronophthisis-like nephropathy 1

disease

On this page

Also known as nephronophthisis (disease) caused by mutation in XPNPEP3nephronophthisis-like nephropathy type 1NPHP-XPNPEP3NPHPL1XPNPEP3 nephronophthisis (disease)

Summary

Nephronophthisis-like nephropathy 1 (MONDO:0013163) is a disease caused by XPNPEP3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: XPNPEP3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 296

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis-like nephropathy 1
Mondo ID	MONDO:0013163
OMIM	613159
DOID	DOID:0111117
UMLS	C3150419
MedGen	461769
GARD	0018180
Is cancer (heuristic)	no

Also known as: nephronophthisis (disease) caused by mutation in XPNPEP3 · nephronophthisis-like nephropathy 1 · nephronophthisis-like nephropathy type 1 · NPHP-XPNPEP3 · NPHPL1 · XPNPEP3 nephronophthisis (disease)

Data availability: 296 ClinVar variants · 4 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 › nephronophthisis-like nephropathy 1

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

296 retrieved; paginated sample, class counts are floors:

175 uncertain significance, 57 likely benign, 24 benign, 13 conflicting classifications of pathogenicity, 12 likely pathogenic, 8 pathogenic, 7 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3068436	Single allele	LOC130067534	Pathogenic	no assertion criteria provided
1012365	NM_022098.4(XPNPEP3):c.1040G>A (p.Trp347Ter)	XPNPEP3	Pathogenic	no assertion criteria provided
1192531	NM_022098.4(XPNPEP3):c.720dup (p.Gln241fs)	XPNPEP3	Pathogenic	no assertion criteria provided
1415192	NM_022098.4(XPNPEP3):c.85C>T (p.Arg29Ter)	XPNPEP3	Pathogenic	criteria provided, single submitter
2426715	NC_000022.10:g.(?41282297)(41282539_?)del	XPNPEP3	Pathogenic	criteria provided, single submitter
2886078	NM_022098.4(XPNPEP3):c.250C>T (p.Gln84Ter)	XPNPEP3	Pathogenic	criteria provided, single submitter
51	NM_022098.4(XPNPEP3):c.1357G>T (p.Gly453Cys)	XPNPEP3	Pathogenic	criteria provided, single submitter
52	NM_022098.4(XPNPEP3):c.931_934del (p.Asn311fs)	XPNPEP3	Pathogenic	no assertion criteria provided
1012366	NM_022098.4(XPNPEP3):c.645del (p.Ser216fs)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
1497807	NM_022098.4(XPNPEP3):c.1055+2T>G	XPNPEP3	Likely pathogenic	criteria provided, single submitter
2500236	NM_022098.4(XPNPEP3):c.658C>T (p.Gln220Ter)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
2500237	NM_022098.4(XPNPEP3):c.1194_1200del (p.Asp398fs)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3383357	NM_022098.4(XPNPEP3):c.499C>T (p.Arg167Ter)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588056	NM_022098.4(XPNPEP3):c.97del (p.Leu33fs)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588059	NM_022098.4(XPNPEP3):c.130C>T (p.Arg44Ter)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588069	NM_022098.4(XPNPEP3):c.589+1G>T	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588073	NM_022098.4(XPNPEP3):c.760C>T (p.Arg254Ter)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588077	NM_022098.4(XPNPEP3):c.855+1G>A	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3588082	NM_022098.4(XPNPEP3):c.937_938del (p.Leu313fs)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
3767168	NM_022098.4(XPNPEP3):c.466C>T (p.Arg156Ter)	XPNPEP3	Likely pathogenic	criteria provided, single submitter
167851	NM_022098.4(XPNPEP3):c.590-8A>G	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2041308	NM_022098.4(XPNPEP3):c.882C>T (p.Gly294=)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2078337	NM_022098.4(XPNPEP3):c.793-19T>G	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
341668	NM_022098.4(XPNPEP3):c.718A>T (p.Ile240Leu)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
341675	NM_022098.4(XPNPEP3):c.1188T>C (p.Leu396=)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3588051	NM_022098.4(XPNPEP3):c.19G>A (p.Ala7Thr)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
538749	NM_022098.4(XPNPEP3):c.1477C>G (p.Pro493Ala)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632390	NM_022098.4(XPNPEP3):c.856-2A>G	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695160	NM_022098.4(XPNPEP3):c.817A>G (p.Ser273Gly)	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
696213	NM_022098.4(XPNPEP3):c.1056-9C>T	XPNPEP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
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

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
XPNPEP3	HGNC:28052	ENSG00000196236	Q9NQH7	Xaa-Pro aminopeptidase 3	gencc,clinvar

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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

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

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
bronchial epithelial cell	1
buccal mucosa cell	1
sperm	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XPNPEP3	2,395

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XPNPEP3	Q9NQH7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
glomerular filtration	1	936.2×	0.003	XPNPEP3
protein processing	1	170.2×	0.009	XPNPEP3
proteolysis	1	34.2×	0.029	XPNPEP3

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
XPNPEP3	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: 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	1	XPNPEP3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
XPNPEP3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: XPNPEP3