MN1

Chr 22AD

MN1 proto-oncogene, transcriptional regulator

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

NCBI Gene: 4330 ENSG00000169184 UniProt: Q10571 OMIM: 156100

The MN1 protein is a transcriptional activator that regulates palate development by controlling TBX22 expression and promotes normal skull bone formation through osteoblast maturation. Mutations cause CEBALID syndrome, characterized by craniofacial abnormalities including cleft palate and skull defects, with autosomal dominant inheritance. This gene is extremely intolerant to loss-of-function variants (pLI >0.99), indicating that haploinsufficiency is likely not tolerated in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

CEBALID syndromeMIM #618774

MeningiomaMIM #607174

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · CEBALID syndrome · AD · ClinGen 2025

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.09

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

📖

GeneReview available — MN1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.78 (0.73–0.83)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 0 / 34.0Missense obs/exp: 592 / 759.4Syn Z: 1.30

Background carrier burden — how many people carry a rare variant somewhere in MN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,974 rare PASS variants

Rare truncating (LoF)

1 in 870

87 rare PASS variants

Rare synonymous (reference)

1 in 57

981 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 66	1 in 1,500
South Asian	~43k	1 in 27	1 in 3,700
Remaining (unassigned)	~30k	1 in 46	1 in 370
European (Finnish)	~27k	1 in 150	1 in 1,600
Admixed American	~22k	1 in 42	1 in 250
African / African American	~21k	1 in 43	1 in 700
East Asian	~20k	1 in 43	1 in 980
Ashkenazi Jewish	~13k	1 in 81	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 40	≈ 1 in 690

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓