MN1

Chr 22AD

MN1 proto-oncogene, transcriptional regulator

Also known as: CEBALID, MGCR, MGCR1, MGCR1-PEN, dJ353E16.2

NCBI Gene: 4330ENSG00000169184UniProt: Q10571

Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

CEBALID syndromeMIM #618774
AD
MeningiomaMIM #607174
AD
493
ClinVar variants
50
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— MN1
🧬
Gene-Disease Validity (ClinGen)
CEBALID syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
50 Pathogenic / Likely Pathogenic· 349 VUS of 493 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

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 5.41
OE 0.00 (0.00–0.09)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.16Z-score
OE missense 0.78 (0.73–0.83)
592 obs / 759.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 0 / 34.0Missense obs/exp: 592 / 759.4Syn Z: 1.30

ClinVar Variant Classifications

493 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic19
VUS349
Likely Benign69
Benign16
Conflicting9
31
Pathogenic
19
Likely Pathogenic
349
VUS
69
Likely Benign
16
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
26
0
31
Likely Pathogenic
8
1
10
0
19
VUS
9
323
16
1
349
Likely Benign
0
25
7
37
69
Benign
0
2
8
6
16
Conflicting
—9
Total223516744493

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

View in ClinVar →

Protein Context — Lollipop Plot

MN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MN1-related C-terminal truncation syndrome

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

CEBALID syndrome

MIM #618774

Molecular basis of disorder known

Autosomal dominant

Meningioma

MIM #607174

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MN1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.
Sturm D et al.·Cell
2016
PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum.
Alhalabi KT et al.·Acta Neuropathol
2021
[Circumscribed Astrocytic Gliomas].
Hayashi H et al.·No Shinkei Geka
2023
Distinctive Craniofacial and Oral Anomalies in MN1 C-terminal Truncation Syndrome.
Yu JJ et al.·Chin J Dent Res
2024Review
Novel truncating variant of MN1 penultimate exon identified in a Chinese patient with newly recognized MN1 C-terminal truncation syndrome: Case report and literature review.
Zhao A et al.·Int J Dev Neurosci
2022Case report
MN1 rearrangement in astroblastoma: study of eight cases and review of literature.
Mhatre R et al.·Brain Tumor Pathol
2019Review
Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature.
Davidson TB et al.·BMC Med Genet
2012Review
A pediatric cerebral tumor with MN1 alteration and pathological features mimicking carcinoma metastasis: may the terminology "high grade neuroepithelial tumor with MN1 alteration" still be relevant?
Sari R et al.·Childs Nerv Syst
2021Review
Soft tissue sarcoma with MN1 gene fusions: a report of three cases with aggressive clinical behavior.
Saoud C et al.·J Pathol
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AstroblastomaBCOR ITD SarcomaCNS Sarcoma

International Rare Brain Tumor Registry

RECRUITING
NCT05697874Children's National Research InstituteStarted 2023-01-01

External Resources

Links to major genomics databases and tools