MAPKBP1

mitogen-activated protein kinase binding protein 1, the group of WD repeat domain containing

Basic information

Region (hg38): 15:41774434-41827855

Links

ENSG00000137802 ∙ NCBI:23005 ∙ OMIM:616786 ∙ HGNC:29536 ∙ Uniprot:O60336 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• late-onset nephronophthisis (Supportive), mode of inheritance: AR
• nephronophthisis 1 (Supportive), mode of inheritance: AR
• nephronophthisis 20 (Strong), mode of inheritance: AR
• nephronophthisis 20 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis 20	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	28089251

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAPKBP1 gene.

• not_provided (271 variants)
• Inborn_genetic_diseases (179 variants)
• MAPKBP1-related_disorder (43 variants)
• Nephronophthisis_20 (32 variants)
• not_specified (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPKBP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014994.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	83	8	97
missense	1		214	28	8	251
nonsense	4	2				6
start loss			1			1
frameshift		1				1
splice donor/acceptor (+/-2bp)	1	5	1			7
Total	6	8	222	111	16

Highest pathogenic variant AF is 0.000013128873

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPKBP1	protein_coding	protein_coding	ENST00000456763	31	53422

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000210	1.00	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	693	892	0.777	0.0000521	9742
Missense in Polyphen		110	228.3	0.48181		2506
Synonymous	1.38	323	356	0.907	0.0000206	3154
Loss of Function	5.93	23	80.3	0.286	0.00000461	838

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000416	0.000416
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000167	0.000163
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.000124	0.000114
Middle Eastern	0.000167	0.000163
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:22700971). Involved in JNK signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6NS57, ECO:0000269|PubMed:22700971}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:28089251}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0907

Intolerance Scores

• loftool: 0.520
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.16

Haploinsufficiency Scores

• pHI: 0.488
• hipred: Y
• hipred_score: 0.639
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.408

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mapkbp1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of defense response to bacterium;negative regulation of interleukin-8 secretion
• Cellular component: nucleus;cytoplasm;mitotic spindle pole
• Molecular function: protein binding