MAPK8IP2

Chr 22

mitogen-activated protein kinase 8 interacting protein 2

Also known as: IB-2, IB2, JIP2, PRKM8IPL

NCBI Gene: 23542 ENSG00000008735 UniProt: Q13387 OMIM: 607755

This gene encodes JIP2, a scaffold protein that organizes components of the JNK signaling pathway and regulates vesicle transport through interactions with JNK signaling components and motor proteins. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and motor dysfunction. The gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a scaffold protein that is thought to be involved in the regulation of the c-Jun amino-terminal kinase signaling pathway. This protein has been shown to interact with and regulate the activity of MAPK8/JNK1 and MAP2K7/MKK7 kinases. [provided by RefSeq, Jun 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— MAPK8IP2

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 39 VUS of 51 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 5.05

OE 0.00 (0.00–0.10)

Highly constrained

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

Missense Constraint?

2.56Z-score

OE missense 0.67 (0.61–0.73)

317 obs / 473.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.67 (0.61–0.73)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 29.7Missense obs/exp: 317 / 473.7Syn Z: 0.27

This gene — mechanism propensity

0.3196th %ile

GOF

0.4776th %ile

LOF

0.74top 10%

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

LOFprediction above median · LOEUF 0.10

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

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS39

Benign1

Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	39	0	0	39
Likely Benign	0	0	0	0
Benign	0	0	1	1
Total	39	1	1	41

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

View in ClinVar →

150 pathogenic / likely-pathogenic (of 167) ClinVar copy-number / structural variants overlap MAPK8IP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →