MEN1

Chr 11

menin 1

Also known as: MEAI, SCG2

NCBI Gene: 4221 ENSG00000133895 UniProt: O00255

Menin functions as a tumor suppressor scaffold protein that regulates gene expression through histone modification and chromatin structure alteration. Mutations cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant tumor predisposition syndrome characterized by parathyroid adenomas, pancreatic islet tumors, and pituitary adenomas, along with various other neoplasms including carcinoid tumors, lipomas, and angiofibromas. The pathogenic mechanism involves loss of function of the menin tumor suppressor protein.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFamilial multiple endocrine neoplasia type I

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · multiple endocrine neoplasia type 1 · AD · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

291

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.71

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

3.25Z-score

OE missense 0.53 (0.47–0.59)

200 obs / 377.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.53 (0.47–0.59)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 1 / 27.8Missense obs/exp: 200 / 377.7Syn Z: 0.75

Background carrier burden — how many people carry a rare variant somewhere in MEN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

595 rare PASS variants

Rare truncating (LoF)

1 in 3,500

53 rare PASS variants

Rare synonymous (reference)

1 in 130

387 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MEN1. 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 240	1 in 3,800
South Asian	~43k	1 in 130	1 in 2,400
Remaining (unassigned)	~30k	1 in 120	1 in 3,000
European (Finnish)	~27k	1 in 340	1 in 1,700
Admixed American	~22k	1 in 130	1 in 3,700
African / African American	~21k	1 in 180	1 in 1,200
East Asian	~20k	1 in 260	1 in 2,700
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 3,500
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,200

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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓