MAPRE1

Chr 20

microtubule associated protein RP/EB family member 1

Also known as: EB1

MAPRE1 encodes a plus-end tracking protein that binds to growing microtubule ends and regulates microtubule dynamics, spindle positioning during mitosis, and chromosome alignment. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating that heterozygous mutations are likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
8
Pubs (1 yr)
18
P/LP submissions
0%
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMAPRE1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 17 VUS of 42 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.991
Z-score 3.49
OE 0.00 (0.000.21)
Highly constrained

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

Missense Constraint
1.43Z-score
OE missense 0.67 (0.570.79)
102 obs / 151.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.21)
00.351.4
Missense OE0.67 (0.570.79)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 0 / 14.2Missense obs/exp: 102 / 151.7Syn Z: -0.10
DN
0.2997th %ile
GOF
0.4678th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.21

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

42 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS17
14
Pathogenic
4
Likely Pathogenic
17
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
4
0
4
VUS
0
15
2
0
17
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01520035

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

View in ClinVar →

Protein Context — Lollipop Plot

MAPRE1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →