MAPKBP1

Summary

MAPKBP1 (mitogen-activated protein kinase binding protein 1, HGNC:29536) is a protein-coding gene on chromosome 15q15.1, encoding Mitogen-activated protein kinase-binding protein 1 (O60336). Negative regulator of NOD2 function.

This gene encodes a scaffold protein that regulates the JNK (c-Jun N-terminal kinase) and NOD2 (nucleotide-binding oligomerization domain-containing protein 2) signaling pathways. The encoded protein interacts with another related JNK pathway scaffold protein, WDR62, via a conserved dimerization domain, and enhances JNK signaling. This protein may play a role in bacterial immunity by binding to the NOD2 receptor and negatively regulating downstream antibacterial and pro-inflammatory signaling. Mutations in this gene that impair cellular localization of the encoded protein cause a form of nephronophthisis, an autosomal-recessive kidney disorder, in human patients.

Source: NCBI Gene 23005 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephronophthisis 20 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 550 total — 6 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014994

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29536
Approved symbol	MAPKBP1
Name	mitogen-activated protein kinase binding protein 1
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0596, NPHP20
Ensembl gene	ENSG00000137802
Ensembl biotype	protein_coding
OMIM	616786
Entrez	23005

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 9 protein_coding, 9 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000456763, ENST00000457542, ENST00000502292, ENST00000502695, ENST00000503526, ENST00000505061, ENST00000505373, ENST00000506301, ENST00000507147, ENST00000507762, ENST00000508050, ENST00000510535, ENST00000512433, ENST00000512970, ENST00000514566, ENST00000515164, ENST00000905150, ENST00000905151, ENST00000938892, ENST00000938893, ENST00000938894

RefSeq mRNA: 3 — MANE Select: NM_014994 NM_001128608, NM_001265611, NM_014994

CCDS: CCDS32201, CCDS45239, CCDS58359

Canonical transcript exons

ENST00000457542 — 31 exons

Exon	Start	End
ENSE00002083064	41825209	41827855
ENSE00003461456	41818194	41818305
ENSE00003465611	41815259	41815405
ENSE00003467296	41812516	41812653
ENSE00003469865	41799823	41799914
ENSE00003479923	41815624	41815799
ENSE00003480859	41824484	41824569
ENSE00003486929	41822939	41823222
ENSE00003508362	41810883	41810945
ENSE00003517754	41819246	41819379
ENSE00003526365	41813621	41813781
ENSE00003528324	41819595	41819650
ENSE00003536092	41818009	41818084
ENSE00003537230	41821584	41821750
ENSE00003538700	41823447	41824061
ENSE00003547135	41822593	41822677
ENSE00003548814	41821965	41822110
ENSE00003565896	41812919	41813101
ENSE00003571233	41811957	41812127
ENSE00003610113	41816559	41816650
ENSE00003615052	41820832	41821068
ENSE00003621755	41775167	41775389
ENSE00003626706	41822225	41822422
ENSE00003643140	41817388	41817458
ENSE00003653738	41818823	41818957
ENSE00003670940	41817614	41817735
ENSE00003677716	41818519	41818582
ENSE00003680057	41814550	41814739
ENSE00003686621	41816910	41817035
ENSE00003690101	41811178	41811235
ENSE00003849183	41774484	41774610

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9167 / max 415.9739, expressed in 1788 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146208	8.4416	1781
146209	0.4330	223
146212	0.4067	204
146210	0.3733	178
146211	0.2256	94
146213	0.0365	14

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.17	gold quality
cerebellar hemisphere	UBERON:0002245	97.07	gold quality
cerebellar cortex	UBERON:0002129	96.97	gold quality
cerebellum	UBERON:0002037	95.84	gold quality
sural nerve	UBERON:0015488	94.52	gold quality
left testis	UBERON:0004533	93.97	gold quality
right testis	UBERON:0004534	93.85	gold quality
pancreatic ductal cell	CL:0002079	92.33	silver quality
endothelial cell	CL:0000115	91.81	silver quality
secondary oocyte	CL:0000655	91.78	gold quality
oocyte	CL:0000023	91.42	gold quality
gingival epithelium	UBERON:0001949	91.13	silver quality
testis	UBERON:0000473	90.72	gold quality
skin of abdomen	UBERON:0001416	90.48	gold quality
skin of leg	UBERON:0001511	90.13	gold quality
right frontal lobe	UBERON:0002810	89.86	gold quality
lower esophagus mucosa	UBERON:0035834	89.75	gold quality
esophagus mucosa	UBERON:0002469	89.53	gold quality
zone of skin	UBERON:0000014	88.96	gold quality
right lobe of thyroid gland	UBERON:0001119	88.64	gold quality
cervix squamous epithelium	UBERON:0006922	88.60	silver quality
primary visual cortex	UBERON:0002436	88.50	gold quality
esophagus	UBERON:0001043	88.27	gold quality
left lobe of thyroid gland	UBERON:0001120	88.20	gold quality
right ovary	UBERON:0002118	88.00	gold quality
cortical plate	UBERON:0005343	87.87	gold quality
mucosa of stomach	UBERON:0001199	87.82	gold quality
thyroid gland	UBERON:0002046	87.68	gold quality
gingiva	UBERON:0001828	87.57	silver quality
left ovary	UBERON:0002119	87.51	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting MAPKBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6081	99.48	66.07	1446

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 3)

• JNKBP1 and NOD2 are co-expressed in the human intestinal epithelium and in immune cells recruited in the lamina propria, which suggests that JNKBP1 contributes to maintain NOD2-mediated intestinal immune homeostasis. (PMID:22700971)
• We identified mutations in MAPKBP1 as a genetic cause of juvenile or late-onset and cilia-independent nephronophthisis. (PMID:28089251)
• Novel nephronophthisis-associated variants reveal functional importance of MAPKBP1 dimerization for centriolar recruitment. (PMID:32505465)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mapkbp1	ENSMUSG00000033902
rattus_norvegicus	Mapkbp1	ENSRNOG00000007018

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), POC1B (ENSG00000139323), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

Mitogen-activated protein kinase-binding protein 1 — O60336 (reviewed: O60336)

Alternative names: JNK-binding protein 1

All UniProt accessions (4): O60336, D6R9F7, D6RAI2, D6RHX7

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of NOD2 function. It down-regulates NOD2-induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response. Involved in JNK signaling pathway.

Subunit / interactions. Can form homodimers (via C-terminus). Interacts (via C-terminus) with WDR62 (via C-terminus). Interacts with MAPK9. Interacts (via N-terminus) with NOD2; the interaction is enhanced in presence of muramyl dipeptide (MDP). Interacts with MAPK10.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Spindle pole.

Tissue specificity. Expressed in intestinal mucosa, where it is detected in epithelial cells, endothelial cells, smooth muscle cells and immune cells, such as lymphocytes. Expressed in kidney.

Disease relevance. Nephronophthisis 20 (NPHP20) [MIM:617271] A form of nephronophthisis, an autosomal recessive chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. Some patients have cystic kidneys of normal size and no extrarenal manifestations, whereas others have enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis. NPHP20 patients do not show extrarenal manifestations or evidence of a ciliopathy, such as situs inversus or polydactyly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal WD40 domain is necessary for the interaction with NOD2 and down-regulation of NOD2 function.

Isoforms (6)

UniProt ID	Names	Canonical?
O60336-1	1	yes
O60336-2	2
O60336-3	3
O60336-4	4
O60336-5	5
O60336-6	6

RefSeq proteins (3): NP_001122080, NP_001252540, NP_055809* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR055292	MABP1	Family
IPR056161	WD40_MABP1-WDR62_1st	Domain
IPR056162	WD40_MABP1-WDR62_2nd	Domain
IPR056364	WDR62-MABP1_CC	Domain

Pfam: PF24780, PF24782, PF24795

UniProt features (41 total): repeat 12, compositionally biased region 8, splice variant 7, region of interest 4, sequence variant 4, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60336-F1	62.82	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 1198

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_255, AAGCCAT_MIR135A_MIR135B, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, MODULE_317, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, FOSTER_TOLERANT_MACROPHAGE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_JNK_CASCADE

GO Biological Process (6): negative regulation of interleukin-8 production (GO:0032717), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of JNK cascade (GO:0046330), negative regulation of defense response to bacterium (GO:1900425), translational initiation (GO:0006413), regulation of intracellular signal transduction (GO:1902531)

GO Molecular Function (2): translation initiation factor activity (GO:0003743), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitotic spindle pole (GO:0097431), spindle pole (GO:0000922), nucleus (GO:0005634), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
intracellular membraneless organelle	2
negative regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
defense response to bacterium	1
regulation of defense response to bacterium	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
regulation of signal transduction	1
intracellular signal transduction	1
translational initiation	1
translation factor activity	1
binding	1
intracellular anatomical structure	1
spindle pole	1
mitotic spindle	1
spindle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPKBP1	MAPK9	P45984	503
MAPKBP1	JUN	P05412	492
MAPKBP1	ANKS6	Q68DC2	484
MAPKBP1	MAPK8	P45983	448
MAPKBP1	RCAN3	Q9UKA8	440
MAPKBP1	NPHP1	O15259	419
MAPKBP1	SDCCAG8	Q86SQ7	384
MAPKBP1	CCDC172	P0C7W6	376
MAPKBP1	CFAP418	Q96NL8	363
MAPKBP1	NEK8	Q86SG6	352
MAPKBP1	SLC25A26	Q70HW3	352
MAPKBP1	WDR19	Q8NEZ3	347
MAPKBP1	AAMP	Q13685	336
MAPKBP1	NME7	Q9Y5B8	334
MAPKBP1	UNC5CL	Q8IV45	331
MAPKBP1	KPNB1	Q14974	331

IntAct

228 interactions, top by confidence:

A	B	Type	Score
GLRX3	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	KRT31	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	MDFI	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-12	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	GLRX3	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
MDFI	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
MAPKBP1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (82): MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), MAPKBP1 (Two-hybrid), ADAMTSL4 (Two-hybrid), TEX11 (Two-hybrid)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RUS2, O43379, O60336, P58742, Q08BB3, Q0VBY8, Q148I1, Q15334, Q3MHH0, Q3SZD4, Q3U3T8, Q499N3, Q4R3J7, Q4VBE8, Q5FW06, Q5QP82, Q5RCX2, Q5T6F0, Q5U4D9, Q5U4F6, Q5VW00, Q5ZJL7, Q63ZP7, Q6AX81, Q6AY87, Q6NS57, Q6NWH1, Q6P1M3, Q6P809, Q7Z5U6, Q80Y17, Q86W42, Q8AVS9, Q8BGW4, Q8BGZ3, Q8C5V5, Q8HXL3, Q8K4K5

Diamond homologs: O43379, O60336, Q3U3T8, Q6DFF9, Q6NS57, Q8HXL3, Q9AV81, Q6CG48

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	22	29.9×	2e-26
Formation of the cornified envelope	6	12.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	5	43.0×	1e-05
intermediate filament organization	6	36.1×	4e-06
epithelial cell differentiation	5	21.9×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

550 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	7
Uncertain significance	251
Likely benign	178
Benign	44

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
374915	NM_014994.3(MAPKBP1):c.592C>T (p.Arg198Ter)	Pathogenic
374916	NM_014994.3(MAPKBP1):c.4375C>T (p.Arg1459Ter)	Pathogenic
374917	NM_014994.3(MAPKBP1):c.1300C>T (p.Arg434Ter)	Pathogenic
374918	NM_014994.3(MAPKBP1):c.1613G>A (p.Arg538Gln)	Pathogenic
374919	NM_014994.3(MAPKBP1):c.2426-1G>A	Pathogenic
374920	NM_014994.3(MAPKBP1):c.2809C>T (p.Gln937Ter)	Pathogenic
2810405	NM_014994.3(MAPKBP1):c.1904+1G>A	Likely pathogenic
3044490	NM_014994.3(MAPKBP1):c.2156+1G>A	Likely pathogenic
3065329	NM_014994.3(MAPKBP1):c.2227C>T (p.Gln743Ter)	Likely pathogenic
3779832	NM_014994.3(MAPKBP1):c.4299+1G>A	Likely pathogenic
4056601	NM_014994.3(MAPKBP1):c.2092+1G>A	Likely pathogenic
4087723	NM_014994.3(MAPKBP1):c.2885+2C>T	Likely pathogenic
800821	NM_014994.3(MAPKBP1):c.934C>T (p.Arg312Ter)	Likely pathogenic

SpliceAI

5855 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41775386:CAAGG:C	donor_loss	1.0000
15:41775387:AAGGT:A	donor_loss	1.0000
15:41775388:AGG:A	donor_loss	1.0000
15:41775390:G:GA	donor_loss	1.0000
15:41775391:T:A	donor_loss	1.0000
15:41799913:GG:G	donor_gain	1.0000
15:41799914:GG:G	donor_gain	1.0000
15:41810879:TCAGG:T	acceptor_loss	1.0000
15:41810882:G:GT	acceptor_loss	1.0000
15:41810882:GGT:G	acceptor_gain	1.0000
15:41810941:TCCAG:T	donor_loss	1.0000
15:41810942:CCAG:C	donor_loss	1.0000
15:41810943:CAGG:C	donor_loss	1.0000
15:41810944:AGG:A	donor_loss	1.0000
15:41810945:GGTAA:G	donor_loss	1.0000
15:41810946:GTAA:G	donor_loss	1.0000
15:41810947:T:G	donor_loss	1.0000
15:41811176:A:AG	acceptor_gain	1.0000
15:41811177:G:GG	acceptor_gain	1.0000
15:41811952:TGCAG:T	acceptor_gain	1.0000
15:41811954:CAG:C	acceptor_gain	1.0000
15:41811954:CAGA:C	acceptor_loss	1.0000
15:41811955:A:AG	acceptor_gain	1.0000
15:41811955:AGA:A	acceptor_gain	1.0000
15:41811955:AGAGT:A	acceptor_gain	1.0000
15:41811956:G:GA	acceptor_gain	1.0000
15:41811956:G:T	acceptor_loss	1.0000
15:41811956:GA:G	acceptor_gain	1.0000
15:41811956:GAG:G	acceptor_gain	1.0000
15:41811956:GAGT:G	acceptor_gain	1.0000

AlphaMissense

9761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41799830:T:C	L41S	1.000
15:41799902:C:A	A65D	1.000
15:41799913:G:T	G69W	1.000
15:41811225:T:A	V106D	1.000
15:41811970:C:A	P114H	1.000
15:41811979:G:C	R117P	1.000
15:41811982:T:A	V118D	1.000
15:41811984:T:A	W119R	1.000
15:41811984:T:C	W119R	1.000
15:41812078:T:A	V150D	1.000
15:41812086:G:C	G153R	1.000
15:41812087:G:A	G153D	1.000
15:41812099:A:T	D157V	1.000
15:41812108:T:A	V160D	1.000
15:41812116:T:A	W163R	1.000
15:41812116:T:C	W163R	1.000
15:41812540:A:G	K175E	1.000
15:41812542:G:C	K175N	1.000
15:41812542:G:T	K175N	1.000
15:41812592:T:C	F192S	1.000
15:41812595:T:A	V193D	1.000
15:41812603:G:C	G196R	1.000
15:41812604:G:A	G196D	1.000
15:41812604:G:T	G196V	1.000
15:41812610:G:C	R198P	1.000
15:41812618:A:G	K201E	1.000
15:41812620:A:C	K201N	1.000
15:41812620:A:T	K201N	1.000
15:41812621:T:C	F202L	1.000
15:41812622:T:C	F202S	1.000

dbSNP variants (sampled 300 via entrez): RS1000005359 (15:41825200 C>A), RS1000088224 (15:41810961 T>C), RS1000088657 (15:41787107 G>A), RS1000155882 (15:41789102 C>G,T), RS1000202086 (15:41811617 G>A), RS1000218103 (15:41804758 C>G,T), RS1000365200 (15:41818808 G>T), RS1000578177 (15:41814578 A>G), RS1000648835 (15:41777532 G>A), RS1000708983 (15:41813158 C>A,G,T), RS1000785292 (15:41777038 G>A), RS1000824565 (15:41811343 C>G), RS1000844058 (15:41793680 G>C), RS1000956142 (15:41826619 G>A), RS1001003521 (15:41806432 G>A)

Disease associations

OMIM: gene MIM:616786 | disease phenotypes: MIM:617271

GenCC curated gene-disease

Disease	Classification	Inheritance
nephronophthisis 20	Definitive	Autosomal recessive
late-onset nephronophthisis	Supportive	Autosomal recessive
nephronophthisis 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nephronophthisis 20	Definitive	AR

Mondo (3): nephronophthisis 20 (MONDO:0014997), late-onset nephronophthisis (MONDO:0019742), nephronophthisis 1 (MONDO:0009728)

Orphanet (0):

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000107	Renal cyst
HP:0002650	Scoliosis
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003774	Stage 5 chronic kidney disease
HP:0011462	Young adult onset

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST006586_34	Urinary albumin excretion	2.000000e-12
GCST007094_223	Diastolic blood pressure	4.000000e-13
GCST007483_6	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-06
GCST007487_56	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-08
GCST007502_43	Waist-to-hip ratio adjusted for BMI (additive genetic model)	8.000000e-06
GCST90000025_209	Appendicular lean mass	9.000000e-14
GCST90020024_481	A body shape index	2.000000e-08
GCST90020024_482	A body shape index	5.000000e-10
GCST90020025_445	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020025_447	Waist-to-hip ratio adjusted for BMI	7.000000e-13
GCST90020025_448	Waist-to-hip ratio adjusted for BMI	6.000000e-11
GCST90020025_449	Waist-to-hip ratio adjusted for BMI	5.000000e-11
GCST90020027_623	Waist-hip index	2.000000e-09
GCST90020027_625	Waist-hip index	1.000000e-12
GCST90020027_626	Waist-hip index	1.000000e-10
GCST90020027_627	Waist-hip index	8.000000e-11
GCST90020029_287	Waist circumference adjusted for body mass index	5.000000e-11
GCST90020029_288	Waist circumference adjusted for body mass index	7.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0006336	diastolic blood pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537699	Nephronophthisis, familial juvenile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	affects localization, affects binding, decreases reaction	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methapyrilene	increases methylation	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XQ30	HAP1 MAPKBP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies