Nephronophthisis 20

Summary

Nephronophthisis 20 (MONDO:0014997) is a disease caused by MAPKBP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MAPKBP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 20
Mondo ID	MONDO:0014997
OMIM	617271
DOID	DOID:0111127
UMLS	C4310640
MedGen	934607
GARD	0018181
Is cancer (heuristic)	no

Also known as: MAPKBP1 nephronophthisis (disease) · nephronophthisis (disease) caused by mutation in MAPKBP1 · nephronophthisis 20 · nephronophthisis type 20 · NPHP20

Data availability: 32 ClinVar variants · 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 › nephronophthisis 20

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, late-onset nephronophthisis, 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

ClinVar germline variants

32 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 6 pathogenic, 5 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 benign, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1526225	NM_014994.3(MAPKBP1):c.1270_1271del (p.Ser424fs)	MAPKBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374915	NM_014994.3(MAPKBP1):c.592C>T (p.Arg198Ter)	MAPKBP1	Pathogenic	no assertion criteria provided
374916	NM_014994.3(MAPKBP1):c.4375C>T (p.Arg1459Ter)	MAPKBP1	Pathogenic	criteria provided, single submitter
374917	NM_014994.3(MAPKBP1):c.1300C>T (p.Arg434Ter)	MAPKBP1	Pathogenic	no assertion criteria provided
374918	NM_014994.3(MAPKBP1):c.1613G>A (p.Arg538Gln)	MAPKBP1	Pathogenic	no assertion criteria provided
374919	NM_014994.3(MAPKBP1):c.2426-1G>A	MAPKBP1	Pathogenic	no assertion criteria provided
374920	NM_014994.3(MAPKBP1):c.2809C>T (p.Gln937Ter)	MAPKBP1	Pathogenic	no assertion criteria provided
3065329	NM_014994.3(MAPKBP1):c.2227C>T (p.Gln743Ter)	MAPKBP1	Likely pathogenic	criteria provided, single submitter
3779832	NM_014994.3(MAPKBP1):c.4299+1G>A	MAPKBP1	Likely pathogenic	criteria provided, single submitter
4056601	NM_014994.3(MAPKBP1):c.2092+1G>A	MAPKBP1	Likely pathogenic	criteria provided, single submitter
4087723	NM_014994.3(MAPKBP1):c.2885+2C>T	MAPKBP1	Likely pathogenic	criteria provided, single submitter
800821	NM_014994.3(MAPKBP1):c.934C>T (p.Arg312Ter)	MAPKBP1	Likely pathogenic	no assertion criteria provided
1032645	NM_014994.3(MAPKBP1):c.1585+15C>T	MAPKBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1336589	NM_014994.3(MAPKBP1):c.2519C>A (p.Ala840Glu)	MAPKBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030172	NM_014994.3(MAPKBP1):c.2230C>T (p.Arg744Cys)	MAPKBP1	Uncertain significance	criteria provided, single submitter
1030173	NM_014994.3(MAPKBP1):c.3662C>T (p.Ala1221Val)	MAPKBP1	Uncertain significance	criteria provided, single submitter
1032647	NM_014994.3(MAPKBP1):c.3998G>C (p.Ser1333Thr)	MAPKBP1	Uncertain significance	criteria provided, single submitter
1032648	NM_014994.3(MAPKBP1):c.97G>C (p.Glu33Gln)	MAPKBP1	Uncertain significance	criteria provided, single submitter
1462825	NM_014994.3(MAPKBP1):c.227A>G (p.Asn76Ser)	MAPKBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805864	NM_014994.3(MAPKBP1):c.1426A>G (p.Ile476Val)	MAPKBP1	Uncertain significance	criteria provided, single submitter
2582421	NM_014994.3(MAPKBP1):c.260A>G (p.Asn87Ser)	MAPKBP1	Uncertain significance	criteria provided, single submitter
3123364	NM_014994.3(MAPKBP1):c.1252C>T (p.Arg418Cys)	MAPKBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393416	NM_014994.3(MAPKBP1):c.2402C>T (p.Ala801Val)	MAPKBP1	Uncertain significance	criteria provided, single submitter
3577099	NM_014994.3(MAPKBP1):c.137G>A (p.Gly46Glu)	MAPKBP1	Uncertain significance	criteria provided, single submitter
3577100	NM_014994.3(MAPKBP1):c.4337G>A (p.Arg1446Gln)	MAPKBP1	Uncertain significance	criteria provided, single submitter
3779831	NM_014994.3(MAPKBP1):c.206+5G>A	MAPKBP1	Uncertain significance	criteria provided, single submitter
4077075	NM_014994.3(MAPKBP1):c.1586-2A>C	MAPKBP1	Uncertain significance	criteria provided, single submitter
4077093	NM_014994.3(MAPKBP1):c.1948G>C (p.Gly650Arg)	MAPKBP1	Uncertain significance	criteria provided, single submitter
917948	NM_014994.3(MAPKBP1):c.3304C>T (p.Arg1102Cys)	MAPKBP1	Uncertain significance	criteria provided, single submitter
728235	NM_014994.3(MAPKBP1):c.4030G>T (p.Gly1344Cys)	MAPKBP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MAPKBP1	Definitive	Autosomal recessive	nephronophthisis 20	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAPKBP1	Orphanet:93589	Late-onset nephronophthisis
MAPKBP1	Orphanet:93592	Juvenile 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
MAPKBP1	HGNC:29536	ENSG00000137802	O60336	Mitogen-activated protein kinase-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAPKBP1	Mitogen-activated protein kinase-binding protein 1	Negative regulator of NOD2 function.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAPKBP1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAPKBP1	251	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPKBP1	1,056

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAPKBP1	O60336	62.82

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
negative regulation of defense response to bacterium	1	5617.3×	7e-04	MAPKBP1
negative regulation of interleukin-8 production	1	991.3×	0.002	MAPKBP1
negative regulation of canonical NF-kappaB signal transduction	1	172.0×	0.006	MAPKBP1
positive regulation of JNK cascade	1	163.6×	0.006	MAPKBP1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
MAPKBP1	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	1	MAPKBP1

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)
MAPKBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.