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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOFmechanismADLOEUF 0.092 OMIM phenotypes

Clinical Summary— MN1

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Gene-Disease Validity (ClinGen)

CEBALID syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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 OE0.00 (0.00–0.09)

0≤0.351.4

Missense OE0.78 (0.73–0.83)

0≤0.61.4

Synonymous OE0.91

0≤1.21.6

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateMN1-related neurodevelopmental disorder with or without cleft palateLOFAD

strongMN1-related C-terminal truncation syndromeLOFAD

0.2299th %ile

GOF

0.2099th %ile

LOF

0.88top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.09

GOF1 literature citation

Literature Evidence

GOFMN1 C-terminal truncation (MCTT) syndrome is a newly recognized neurodevelopmental disorder due to heterozygous gain-of-function C-terminal truncating mutations clustering in the last or penultimate exon of MN1 gene (MIM: 156100).PMID:34708882

LOFThe mutations or deletions in this second group of patients were predicted to cause MN1 haploinsufficiency, and the phenotype was somewhat different than that observed in the first group of patients.PMID:31834374

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.