MAPK8IP3

mitogen-activated protein kinase 8 interacting protein 3, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 16:1706166-1770351

Links

ENSG00000138834

∙ NCBI:23162 ∙ OMIM:605431 ∙ HGNC:6884 ∙ Uniprot:Q9UPT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder with or without variable brain abnormalities; NEDBA (Strong), mode of inheritance: AD
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA (Strong), mode of inheritance: AD
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA (Strong), mode of inheritance: AD
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with or without variable brain abnormalities	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	Craniofacial; Musculoskeletal; Neurologic	30612693; 30945334

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAPK8IP3 gene.

not_provided (207 variants)
Inborn_genetic_diseases (176 variants)
Neurodevelopmental_disorder_with_or_without_variable_brain_abnormalities%3B_NEDBA (91 variants)
MAPK8IP3-related_disorder (52 variants)
not_specified (18 variants)
Neurodevelopmental_disorder (3 variants)
See_cases (3 variants)
Intellectual_disability (2 variants)
Incidental_Discovery (1 variants)
Global_developmental_delay (1 variants)
2-3_finger_cutaneous_syndactyly (1 variants)
Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK8IP3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001318852.2. 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			1 clinvar	58 clinvar	7 clinvar	66
missense		10 clinvar	304 clinvar	52 clinvar		366
nonsense	3 clinvar	2 clinvar	5 clinvar			10
start loss						0
frameshift	1 clinvar	1 clinvar	4 clinvar			6
splice donor/acceptor (+/-2bp)		5 clinvar	3 clinvar	1 clinvar		9
Total	4	18	317	111	7

Highest pathogenic variant AF is 0.0000013683353

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPK8IP3	protein_coding	protein_coding	ENST00000250894	32	64135

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.99e-8	124732	0	48	124780	0.000192

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.88	663	908	0.731	0.0000620	8685
Missense in Polyphen		133	288.78	0.46056		2743
Synonymous	-2.54	453	389	1.16	0.0000296	2622
Loss of Function	7.19	5	69.9	0.0715	0.00000340	756

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000285	0.000284
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000603	0.0000556
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000333	0.000327
Middle Eastern	0.0000603	0.0000556
South Asian	0.00	0.00
Other	0.000178	0.000165

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 (PubMed:12189133). May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604). {ECO:0000250|UniProtKB:Q9ESN9, ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:21775604}.;
Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Ncore;MAPK Signaling Pathway;Arf6 trafficking events;Signaling events mediated by focal adhesion kinase (Consensus)

Recessive Scores

pRec: 0.189

Intolerance Scores

loftool: 0.0583
rvis_EVS: -2.65
rvis_percentile_EVS: 0.77

Haploinsufficiency Scores

pHI: 0.318
hipred: Y
hipred_score: 0.783
ghis: 0.694

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mapk8ip3
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; 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); vision/eye phenotype;

Zebrafish Information Network

Gene name: mapk8ip3
Affected structure: posterior lateral line
Phenotype tag: abnormal
Phenotype quality: swollen

Gene ontology

Biological process: activation of JUN kinase activity;vesicle-mediated transport;axon regeneration;regulation of JNK cascade;axon development;anterograde axonal protein transport
Cellular component: Golgi membrane;cytoplasm;axon;dendrite;growth cone;cytoplasmic vesicle;cell body;perinuclear region of cytoplasm;axon cytoplasm
Molecular function: MAP-kinase scaffold activity;protein binding;JUN kinase binding;kinesin binding;receptor signaling complex scaffold activity