Multiple endocrine neoplasia: genes and variants

Genes linked to Multiple endocrine neoplasia

• MEN1: Menin

  Its menin scaffold coordinates transcriptional and chromatin-regulatory complexes that restrain endocrine-cell proliferation. Germline loss-of-function variants cause multiple endocrine neoplasia type 1 with high risk of parathyroid, pituitary, and pancreatic neuroendocrine tumors.

  111 disease-causing and 884 uncertain variants in MEN1 are linked to Multiple endocrine neoplasia.

• RET: Proto-oncogene tyrosine-protein kinase receptor Ret

  Its activation by GDNF-family ligands guides development of the enteric nervous system, kidney, and other tissues. Activating variants cause multiple endocrine neoplasia type 2 and can drive cancer, whereas loss-of-function variants are an important cause of Hirschsprung disease.

  53 disease-causing and 1,669 uncertain variants in RET are linked to Multiple endocrine neoplasia.

• CDKN1B: Cyclin-dependent kinase inhibitor 1B

  It restrains cell-cycle progression by inhibiting cyclin-CDK complexes and integrates mitogenic and antiproliferative signals. Germline loss-of-function variants cause MEN4, while reduced expression or mislocalization is common in cancer.

  0 disease-causing and 407 uncertain variants in CDKN1B are linked to Multiple endocrine neoplasia.

Weakly linked (only a few uncertain records): ALK and ATM.

Known disease-causing variants in Multiple endocrine neoplasia

Showing 60 of 164.

Uncertain variants in Multiple endocrine neoplasia that look disease-causing

Which prediction tools work for Multiple endocrine neoplasia

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 97 out of 100
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 94 out of 100
• REVEL: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 88 out of 100
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 85 out of 100
• phyloP: 78 out of 100

Same protein, different disease

• Hirschsprung disease is also caused by RET variants; they fall mostly in different places as the Multiple endocrine neoplasia variants (16 disease-causing).

Diseases related to Multiple endocrine neoplasia

• Gastrointestinal stromal tumor, also linked to RET
• Pheochromocytoma, also linked to RET
• Ovarian cancer, also linked to RET
• Colorectal cancer, also linked to RET
• Non-small cell lung carcinoma, also linked to RET
• Hirschsprung disease, also linked to RET
• Familial medullary thyroid carcinoma, also linked to RET
• Hepatocellular carcinoma, also linked to RET
• Familial hyperparathyroidism or Hypocalciuric hypercalcaemia, also linked to RET
• MEN2 phenotype: Unclassified, also linked to RET
• Renal cell carcinoma, also linked to RET

Frequently asked questions

Which genes are linked to Multiple endocrine neoplasia?

In CATVariant, Multiple endocrine neoplasia is linked to 3 analyzed proteins: MEN1 (Menin), RET (Proto-oncogene tyrosine-protein kinase receptor Ret) and CDKN1B (Cyclin-dependent kinase inhibitor 1B).

How many genetic variants are linked to Multiple endocrine neoplasia?

3,194 variants: 164 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2,961 are of uncertain significance or have conflicting reports.

Which uncertain variants in Multiple endocrine neoplasia look disease-causing?

41 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example MEN1 G156S, MEN1 A176T, MEN1 S253L, MEN1 Q141R and MEN1 A164S. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Multiple endocrine neoplasia?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 87 disease-causing and 36 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

Download every variant as CSV · Browse all diseases · Methods · About the Center