MAPK8IP3

Chr 16

mitogen-activated protein kinase 8 interacting protein 3

Also known as: JIP-3, JIP3, JSAP1, NEDBA, SYD2, syd

NCBI Gene: 23162ENSG00000138834UniProt: Q9UPT6

The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with or without variable brain abnormalities

Clinical highlights

Gene-disease validity (ClinGen)
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
11
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.15
LOEUF· LoF intol.
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.15LOEUF
pLI 1.000
Z-score 7.19
OE 0.07 (0.04–0.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
2.88Z-score
OE missense 0.73 (0.69–0.78)
663 obs / 907.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.07 (0.04–0.15)
0≤0.351.4
Missense OE?0.73 (0.69–0.78)
0≤0.61.4
Synonymous OE?1.16
0≤1.21.6
LoF obs/exp: 5 / 69.9Missense obs/exp: 663 / 907.5Syn Z: -2.54

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MAPK8IP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients