MAPK8IP1

mitogen-activated protein kinase 8 interacting protein 1

Basic information

Region (hg38): 11:45885651-45906465

Previous symbols: [ "PRKM8IP" ]

Links

ENSG00000121653 ∙ NCBI:9479 ∙ OMIM:604641 ∙ HGNC:6882 ∙ Uniprot:Q9UQF2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diabetes mellitus, noninsulin-dependent (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the MAPK8IP1 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			42		1	43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1		1
Total	0	0	42	5	2

Variants in MAPK8IP1

This is a list of pathogenic ClinVar variants found in the MAPK8IP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-45885816-C-T		MAPK8IP1-related disorder	Likely benign (Mar 18, 2019)
11-45885839-G-C		not specified	Uncertain significance (Apr 19, 2023)
11-45885852-G-C		not specified	Uncertain significance (Feb 03, 2022)
11-45885872-G-C		not specified	Uncertain significance (May 09, 2023)
11-45885902-G-C		not specified	Uncertain significance (Sep 14, 2022)
11-45885908-C-T		not specified	Uncertain significance (Oct 05, 2023)
11-45898159-G-A		Diabetes mellitus type 2, susceptibility to	risk factor (Mar 01, 2000)
11-45898189-G-A		not specified	Uncertain significance (Mar 20, 2024)
11-45900139-C-T		not specified	Uncertain significance (May 27, 2022)
11-45900154-T-C		not specified	Uncertain significance (Apr 12, 2023)
11-45900157-T-C		not specified	Uncertain significance (Dec 01, 2022)
11-45900164-G-GGGC			Uncertain significance (-)
11-45900197-C-T		MAPK8IP1-related disorder	Likely benign (Apr 19, 2021)
11-45900260-G-C		not specified	Uncertain significance (May 11, 2022)
11-45900295-C-T		not specified	Uncertain significance (May 25, 2022)
11-45900305-G-T		MAPK8IP1-related disorder	Likely benign (Jan 05, 2023)
11-45900322-C-G		not specified	Uncertain significance (Dec 21, 2023)
11-45900394-C-T		not specified	Uncertain significance (May 26, 2023)
11-45900406-A-G		not specified	Uncertain significance (Nov 17, 2023)
11-45902013-C-T		not specified	Uncertain significance (Oct 25, 2022)
11-45902038-G-A		not specified	Uncertain significance (Oct 06, 2021)
11-45902378-A-C		not specified	Uncertain significance (Apr 26, 2024)
11-45902381-C-T		not specified	Uncertain significance (Mar 15, 2024)
11-45902420-C-T		not specified	Uncertain significance (May 06, 2024)
11-45902425-C-G		not specified	Uncertain significance (Jan 20, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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