Medulloblastoma: genes and variants

Genes linked to Medulloblastoma

• CTNNB1: Catenin beta-1

  It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder.

  4 disease-causing and 0 uncertain variants in CTNNB1 are linked to Medulloblastoma.

• SUFU: Suppressor of fused homolog

  It restrains GLI transcription factors and thereby keeps Hedgehog signaling off when pathway activation is absent. Germline loss-of-function variants predispose particularly to infant desmoplastic medulloblastoma and can also cause developmental Hedgehog-pathway phenotypes.

  0 disease-causing and 511 uncertain variants in SUFU are linked to Medulloblastoma.

• BRCA2: Breast cancer type 2 susceptibility protein

  It loads RAD51 onto damaged DNA to enable homologous recombination and also protects stressed replication forks from degradation. Germline loss-of-function variants strongly predispose to breast, ovarian, prostate, pancreatic, and other cancers.

  0 disease-causing and 0 uncertain variants in BRCA2 are linked to Medulloblastoma.

• KMT2C: Histone-lysine N-methyltransferase 2C

  It helps establish enhancer-associated H3K4 methylation and thereby controls lineage-specific transcription together with other COMPASS-family proteins. Somatic loss-of-function alterations are frequent across cancers, while germline variants can cause neurodevelopmental phenotypes.

  0 disease-causing and 0 uncertain variants in KMT2C are linked to Medulloblastoma.

• KMT2D: Histone-lysine N-methyltransferase 2D

  It deposits enhancer-associated H3K4 methylation and coordinates developmental gene expression through chromatin regulatory complexes. Heterozygous loss-of-function variants are a major cause of Kabuki syndrome, and somatic mutations are common in several lymphomas and solid tumors.

  0 disease-causing and 0 uncertain variants in KMT2D are linked to Medulloblastoma.

• PTCH1: Protein patched homolog 1

  It suppresses Smoothened in the absence of Hedgehog ligands and thereby keeps Hedgehog developmental signaling inactive until an appropriate signal is received. Germline loss-of-function variants cause Gorlin syndrome, while somatic pathway activation drives basal-cell carcinoma and other tumors.

  0 disease-causing and 0 uncertain variants in PTCH1 are linked to Medulloblastoma.

• SMARCA4: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4

  Its ATPase activity drives nucleosome remodeling in BAF-family complexes and thereby controls access to regulatory DNA. Germline pathogenic variants cause Coffin-Siris syndrome or rhabdoid-tumor predisposition, while somatic loss defines several aggressive cancers.

  0 disease-causing and 0 uncertain variants in SMARCA4 are linked to Medulloblastoma.

• SMO: Protein smoothened

  It transmits Hedgehog signals across the membrane after inhibition by PTCH1 is relieved, activating GLI-dependent developmental transcription. Activating variants or upstream pathway loss can drive basal-cell carcinoma, medulloblastoma, and other Hedgehog-dependent tumors.

  0 disease-causing and 0 uncertain variants in SMO are linked to Medulloblastoma.

Weakly linked (only a few uncertain records): ARID1A and RB1.

Known disease-causing variants in Medulloblastoma

Same protein, different disease

• Pilomatrixoma is also caused by CTNNB1 variants; they fall in the same places as the Medulloblastoma variants (8 disease-causing).
• Severe intellectual disability-progressive spastic diplegia syndrome is also caused by CTNNB1 variants; they fall mostly in different places as the Medulloblastoma variants (5 disease-causing).

Diseases related to Medulloblastoma

• Ovarian cancer, also linked to BRCA2, CTNNB1 and PTCH1
• Gorlin syndrome, also linked to PTCH1 and SUFU
• Ovarian neoplasm, also linked to BRCA2 and CTNNB1
• Basal cell nevus syndrome 1, also linked to PTCH1 and SUFU
• Basal cell carcinoma, also linked to PTCH1 and SMO
• Kabuki syndrome, also linked to KMT2D
• Acute myeloid leukemia, also linked to SMO
• Fanconi anemia, also linked to BRCA2
• Colorectal cancer, also linked to CTNNB1
• Malignant tumor of urinary bladder, also linked to CTNNB1
• Non-small cell lung carcinoma, also linked to SMARCA4
• Coffin-Siris syndrome, also linked to SMARCA4

Frequently asked questions

Which genes are linked to Medulloblastoma?

In CATVariant, Medulloblastoma is linked to 8 analyzed proteins: CTNNB1 (Catenin beta-1), SUFU (Suppressor of fused homolog), BRCA2 (Breast cancer type 2 susceptibility protein), KMT2C (Histone-lysine N-methyltransferase 2C), KMT2D (Histone-lysine N-methyltransferase 2D), PTCH1 (Protein patched homolog 1) and 2 more.

How many genetic variants are linked to Medulloblastoma?

541 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 512 are of uncertain significance or have conflicting reports.

Which uncertain variants in Medulloblastoma look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

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.

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