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…
LOFmechanismLOEUF 0.15
Clinical Summary— MAPK8IP3
🧬
Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 364 VUS of 595 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMAPK8IP3-related intellectual disability with variable brain anomaliesLOFAD

This gene — mechanism propensity

DN
0.4289th %ile
GOF
0.4085th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 65% of P/LP variants are LoF · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic15
VUS364
Likely Benign138
Benign23
Conflicting11
5
Pathogenic
15
Likely Pathogenic
364
VUS
138
Likely Benign
23
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
0
0
5
Likely Pathogenic
8
6
1
0
15
VUS
12
341
10
1
364
Likely Benign
4
57
11
66
138
Benign
0
1
10
12
23
Conflicting
—11
Total294053279556

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap MAPK8IP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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