MAPKBP1

Chr 15

mitogen-activated protein kinase binding protein 1

Also known as: JNKBP-1, JNKBP1, NPHP20

NCBI Gene: 23005 ENSG00000137802 UniProt: O60336

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. [provided by RefSeq, May 2017]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNephronophthisis 20

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nephronophthisis 20 · AR · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.000

Z-score 5.93

OE 0.29 (0.20–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.37Z-score

OE missense 0.78 (0.73–0.83)

693 obs / 892.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.41)

0≤0.351.4

Missense OE?0.78 (0.73–0.83)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 23 / 80.3Missense obs/exp: 693 / 892.4Syn Z: 1.38

Background carrier burden — how many people carry a rare variant somewhere in MAPKBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 31

1,735 rare PASS variants

Rare truncating (LoF)

1 in 1,800

165 rare PASS variants

Rare synonymous (reference)

1 in 69

771 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAPKBP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 49	1 in 1,800
South Asian	~43k	1 in 28	1 in 1,500
Remaining (unassigned)	~30k	1 in 30	1 in 3,800
European (Finnish)	~27k	1 in 71	1 in 3,300
Admixed American	~22k	1 in 33	1 in 1,900
African / African American	~21k	1 in 28	1 in 1,200
East Asian	~20k	1 in 48	1 in 1,400
Ashkenazi Jewish	~13k	1 in 86	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 34	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 30 coding exons well covered in gnomAD exomes and genomes.? see exons ↓