MAPRE2

Chr 18AD

microtubule associated protein RP/EB family member 2

Also known as: CSCSC2, EB1, EB2, RP1

NCBI Gene: 10982ENSG00000166974UniProt: Q15555

The MAPRE2 protein stabilizes microtubules and anchors them at centrosomes, ensuring proper mitotic progression and genome stability, and plays roles in neurite growth and cell migration. Mutations cause symmetric circumferential skin creases, congenital, type 2 through autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (LOEUF 0.406), indicating that complete protein loss is likely incompatible with normal development.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Symmetric circumferential skin creases, congenital, 2MIM #616734
AD
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
0.41
LOEUF
LOF
Mechanism· predicted
Clinical Summary— MAPRE2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.41LOEUF
pLI 0.834
Z-score 3.41
OE 0.16 (0.07–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.19Z-score
OE missense 0.33 (0.27–0.41)
59 obs / 179.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.16 (0.07–0.41)
0≤0.351.4
Missense OE0.33 (0.27–0.41)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 3 / 19.1Missense obs/exp: 59 / 179.0Syn Z: 0.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateMAPRE2-related symmetric circumferential skin creases, congenitalOTHERAD
definitiveMAPRE2-related circumferential skin creases, Kunze typeOTHERAR
DN
0.3892th %ile
GOF
0.4481th %ile
LOF
0.62top 25%

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

LOF1 literature citation · LOEUF 0.41

Literature Evidence

LOFFurther, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm).PMID:26637975

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MAPRE2 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
MAPRE2 mutations result in altered human cranial neural crest migration, underlying craniofacial malformations in CSC-KT syndrome
Thues C et al.·Sci Rep
2021
Integrative Analysis of miRNA and mRNA Expression Profiles in Mammary Glands of Holstein Cows Artificially Infected with Staphylococcus aureus
Wang X et al.·Pathogens
2021
Rare Cause of West syndrome secondary to Tubulinopathy due to Congenital Symmetric Circumferential Skin Creases (CSCSC) Kunze Type due to a Novel Variant in MAPRE2 Gene
Gowda VK et al.·Ann Indian Acad Neurol
2022
Genome-wide association study and fine-mapping using imputed sequences to prioritize candidate genes for 30 complex traits in 50,309 Holstein bulls.
Wang J et al.·J Dairy Sci
2025
Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.
Barc J et al.·Nat Genet
2022Functional
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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