Malignant tumor of urinary bladder: genes and variants

Genes linked to Malignant tumor of urinary bladder

• FGFR3: Fibroblast growth factor receptor 3

  It normally restrains growth-plate chondrocyte proliferation while regulating multiple developmental pathways. Activating germline variants cause achondroplasia and related skeletal dysplasias, while somatic activating alterations are common in bladder cancer and some other tumors.

  3 disease-causing and 1 uncertain variants in FGFR3 are linked to Malignant tumor of urinary bladder.

• HRAS: GTPase HRas

  Its GTP-bound state activates RAF-MEK-ERK and other pathways downstream of growth-factor receptors. Somatic activating variants drive several cancers, while germline activating variants cause Costello syndrome.

  2 disease-causing and 3 uncertain variants in HRAS are linked to Malignant tumor of urinary bladder.

• KRAS: GTPase KRas

  A small GTPase that acts as a molecular switch in the RAS-MAPK signaling pathway. By cycling between GDP- and GTP-bound states, it relays growth and survival signals, and activating KRAS variants are common drivers of cancer.

  1 disease-causing and 1 uncertain variants in KRAS are linked to Malignant tumor of urinary bladder.

• ERBB2: Receptor tyrosine-protein kinase erbB-2

  ERBB2, also called HER2, is a cell-surface receptor tyrosine kinase that works with other ERBB receptors to transmit growth signals. It helps organize signaling and cytoskeletal responses, and abnormal ERBB2 activity is a major feature of several cancers.

  6 disease-causing and 0 uncertain variants in ERBB2 are linked to Malignant tumor of urinary bladder.

• ERBB3: Receptor tyrosine-protein kinase erbB-3

  It amplifies neuregulin and ERBB-family signaling primarily by heterodimerizing with catalytically active partners such as HER2 and strongly recruiting PI3K. Persistent signaling can promote tumor growth and resistance to targeted therapy.

  4 disease-causing and 0 uncertain variants in ERBB3 are linked to Malignant tumor of urinary bladder.

• 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.

  2 disease-causing and 0 uncertain variants in CTNNB1 are linked to Malignant tumor of urinary bladder.

• PIK3CA: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

  Its p110-alpha catalytic activity generates PIP3 and activates AKT-dependent growth, survival, and metabolic signaling downstream of many receptors. Activating variants are frequent cancer drivers and, when present mosaically during development, can cause PIK3CA-related overgrowth spectrum.

  1 disease-causing and 0 uncertain variants in PIK3CA are linked to Malignant tumor of urinary bladder.

• RB1: Retinoblastoma-associated protein

  It restrains E2F-dependent transcription and prevents inappropriate G1-to-S cell-cycle progression until proliferative signals are appropriate. Loss of function is a fundamental cancer-driving event, while germline pathogenic variants cause hereditary retinoblastoma and increase risk of additional tumors.

  0 disease-causing and 94 uncertain variants in RB1 are linked to Malignant tumor of urinary bladder.

• TSC1: Hamartin

  Together with TSC2, it restrains RHEB and mTORC1 signaling, preventing inappropriate cell growth when nutrients or growth signals are limited. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors in the brain, kidney, skin, heart, lungs, and other organs.

  0 disease-causing and 0 uncertain variants in TSC1 are linked to Malignant tumor of urinary bladder.

Known disease-causing variants in Malignant tumor of urinary bladder

Which prediction tools work for Malignant tumor of urinary bladder

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

• AlphaMissense: 91 out of 100
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 80 out of 100
• SIFT: 79 out of 100
• MutPred2: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 64 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Lung adenocarcinoma is also caused by ERBB2 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (3 disease-causing).
• FGFR3-related chondrodysplasia is also caused by FGFR3 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (20 disease-causing).
• Hypochondroplasia is also caused by FGFR3 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (15 disease-causing).
• Achondroplasia is also caused by FGFR3 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (9 disease-causing).
• Thanatophoric dysplasia is also caused by FGFR3 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (8 disease-causing).
• Severe achondroplasia-developmental delay-acanthosis nigricans syndrome is also caused by FGFR3 variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (5 disease-causing).
• Costello syndrome is also caused by HRAS variants; they fall partly in the same places as the Malignant tumor of urinary bladder variants (15 disease-causing).
• RASopathy is also caused by HRAS variants; they fall in the same places as the Malignant tumor of urinary bladder variants (6 disease-causing).
• Large congenital melanocytic nevus is also caused by HRAS variants; they fall in the same places as the Malignant tumor of urinary bladder variants (5 disease-causing).
• Epidermal nevus is also caused by HRAS variants; they fall in the same places as the Malignant tumor of urinary bladder variants (3 disease-causing).
• Pilomatrixoma is also caused by CTNNB1 variants; they fall in the same places as the Malignant tumor of urinary bladder 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 Malignant tumor of urinary bladder variants (5 disease-causing).
• Medulloblastoma is also caused by CTNNB1 variants; they fall partly in the same places as the Malignant tumor of urinary bladder variants (4 disease-causing).
• RASopathy is also caused by KRAS variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (23 disease-causing).
• Noonan syndrome is also caused by KRAS variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (16 disease-causing).
• Cardiofaciocutaneous syndrome is also caused by KRAS variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (9 disease-causing).
• Autoimmune lymphoproliferative syndrome is also caused by KRAS variants; they fall partly in the same places as the Malignant tumor of urinary bladder variants (5 disease-causing).
• Non-small cell lung carcinoma is also caused by KRAS variants; they fall mostly in different places as the Malignant tumor of urinary bladder variants (5 disease-causing).

Diseases related to Malignant tumor of urinary bladder

• Colorectal cancer, also linked to CTNNB1, ERBB2, FGFR3, KRAS and 1 more
• Non-small cell lung carcinoma, also linked to ERBB2, ERBB3, KRAS, PIK3CA and 1 more
• Ovarian cancer, also linked to CTNNB1, ERBB2, PIK3CA and TSC1
• Noonan syndrome, also linked to HRAS, KRAS and PIK3CA
• Gastric cancer, also linked to ERBB2, KRAS and PIK3CA
• Ovarian neoplasm, also linked to CTNNB1, ERBB2 and PIK3CA
• Carcinoma of colon, also linked to CTNNB1, FGFR3 and PIK3CA
• Lung adenocarcinoma, also linked to ERBB2, KRAS and RB1
• Lung cancer, also linked to ERBB2, KRAS and PIK3CA
• Hepatocellular carcinoma, also linked to CTNNB1, PIK3CA and RB1
• RASopathy, also linked to HRAS and KRAS
• Noonan syndrome and Noonan-related syndrome, also linked to HRAS and KRAS

Frequently asked questions

Which genes are linked to Malignant tumor of urinary bladder?

In CATVariant, Malignant tumor of urinary bladder is linked to 9 analyzed proteins: FGFR3 (Fibroblast growth factor receptor 3), HRAS (GTPase HRas), KRAS (GTPase KRas), ERBB2 (Receptor tyrosine-protein kinase erbB-2), ERBB3 (Receptor tyrosine-protein kinase erbB-3), CTNNB1 (Catenin beta-1) and 3 more.

How many genetic variants are linked to Malignant tumor of urinary bladder?

127 variants: 19 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 99 are of uncertain significance or have conflicting reports.

Which uncertain variants in Malignant tumor of urinary bladder look disease-causing?

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

Which variant effect predictor works best for Malignant tumor of urinary bladder?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 12 disease-causing and 63 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