MAPK8IP1
mitogen-activated protein kinase 8 interacting protein 1
Basic information
Region (hg38): 11:45885651-45906465
Previous symbols: [ "PRKM8IP" ]
Links
Phenotypes
GenCC
Source:
- diabetes mellitus, noninsulin-dependent (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Diabetes mellitus | AD | 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 | Endocrine | 10700186 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (100 variants)
- not_provided (5 variants)
- MAPK8IP1-related_disorder (5 variants)
- Diabetes_mellitus_type_2,_susceptibility_to (1 variants)
- Type_2_diabetes_mellitus (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK8IP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005456.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 100 | 103 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 100 | 5 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPK8IP1 | protein_coding | protein_coding | ENST00000241014 | 12 | 20815 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000169 | 125595 | 0 | 3 | 125598 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 309 | 392 | 0.788 | 0.0000266 | 4545 |
| Missense in Polyphen | 107 | 158.22 | 0.67625 | 1808 | ||
| Synonymous | 0.0718 | 174 | 175 | 0.993 | 0.0000129 | 1456 |
| Loss of Function | 4.83 | 1 | 29.2 | 0.0343 | 0.00000173 | 334 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000480 | 0.0000462 |
| European (Non-Finnish) | 0.0000179 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK- regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells. {ECO:0000250|UniProtKB:Q9WVI9}.;
- Disease
- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10700186}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
- Pathway
- MAPK signaling pathway - Homo sapiens (human);EGF-Ncore;MAPK Signaling Pathway;Reelin signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.261
Intolerance Scores
- loftool
- 0.0389
- rvis_EVS
- -0.62
- rvis_percentile_EVS
- 17.31
Haploinsufficiency Scores
- pHI
- 0.379
- hipred
- Y
- hipred_score
- 0.800
- ghis
- 0.568
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mapk8ip1
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- regulation of transcription, DNA-templated;JUN phosphorylation;vesicle-mediated transport;negative regulation of JUN kinase activity;regulation of JNK cascade;positive regulation of JNK cascade;regulation of CD8-positive, alpha-beta T cell proliferation;negative regulation of intrinsic apoptotic signaling pathway
- Cellular component
- nucleus;cytoplasm;endoplasmic reticulum membrane;cytosol;plasma membrane;mitochondrial membrane;dendritic growth cone;axonal growth cone;cell body;dentate gyrus mossy fiber;synapse;perinuclear region of cytoplasm
- Molecular function
- protein kinase inhibitor activity;MAP-kinase scaffold activity;protein binding;JUN kinase binding;kinesin binding;mitogen-activated protein kinase kinase binding;mitogen-activated protein kinase kinase kinase binding