JAKMIP1

Chr 4

janus kinase and microtubule interacting protein 1

Also known as: Gababrbp, JAMIP1, MARLIN1

JAKMIP1 encodes a protein that binds GABA receptors and facilitates their microtubule-dependent transport, while also regulating microtubule cytoskeleton rearrangements and JAK1 signaling. Mutations cause autosomal recessive intellectual disability with onset in early childhood. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
89
P/LP submissions
1%
P/LP missense
0.23
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Clinical SummaryJAKMIP1
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
89 unique Pathogenic / Likely Pathogenic· 65 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 5.89
OE 0.12 (0.060.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.89Z-score
OE missense 0.65 (0.590.71)
339 obs / 525.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.060.23)
00.351.4
Missense OE0.65 (0.590.71)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 6 / 51.8Missense obs/exp: 339 / 525.2Syn Z: 1.20
DN
0.6937th %ile
GOF
0.6247th %ile
LOF
0.55top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.23
DNprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic5
VUS65
Likely Benign11
Benign11
Conflicting2
84
Pathogenic
5
Likely Pathogenic
65
VUS
11
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
83
0
84
Likely Pathogenic
0
0
5
0
5
VUS
1
57
7
0
65
Likely Benign
0
4
2
5
11
Benign
0
0
3
8
11
Conflicting
2
Total16210013178

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

View in ClinVar →

Protein Context — Lollipop Plot

JAKMIP1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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