JAKMIP3

Chr 10

Janus kinase and microtubule interacting protein 3

Also known as: C10orf14, C10orf39, Jamip3, NECC2, bA140A10.5

NCBI Gene: 282973ENSG00000188385UniProt: Q5VZ66

The protein binds kinases and microtubules and localizes to the Golgi apparatus and membrane. Mutations cause autosomal recessive neurodevelopmental disorder with progressive microcephaly, seizures, and brain atrophy. This gene is highly constrained against loss-of-function variants (LOEUF 0.40), suggesting that complete loss of protein function is poorly tolerated.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
97
P/LP submissions
0%
P/LP missense
0.40
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— JAKMIP3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
97 unique Pathogenic / Likely Pathogenic· 144 VUS of 256 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.067
Z-score 5.00
OE 0.25 (0.16–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.32Z-score
OE missense 0.84 (0.77–0.91)
425 obs / 508.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.16–0.40)
0≤0.351.4
Missense OE0.84 (0.77–0.91)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 13 / 51.8Missense obs/exp: 425 / 508.8Syn Z: -1.19
DN
0.87top 5%
GOF
0.74top 25%
LOF
0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic5
VUS144
Likely Benign4
92
Pathogenic
5
Likely Pathogenic
144
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
5
0
5
VUS
0
136
8
0
144
Likely Benign
0
2
1
1
4
Benign
0
0
0
0
0
Total01381061245

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

View in ClinVar →

Protein Context — Lollipop Plot

JAKMIP3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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