Urinary bladder cancer: genes and variants

Genes linked to Urinary bladder cancer

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ERBB2 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ERBB3 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in FGFR3 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 3 uncertain variants in HRAS have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in KRAS have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PIK3CA have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 94 uncertain variants in RB1 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• ARID1A: AT-rich interactive domain-containing protein 1A

  It helps BAF chromatin-remodeling complexes open or reposition nucleosomes at regulatory regions and thereby control lineage-specific transcription. Somatic loss is frequent in several cancers, while germline haploinsufficiency can cause Coffin-Siris syndrome.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ARID1A have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• KDM6A: Lysine-specific demethylase 6A

  It removes repressive H3K27 methylation and also contributes to chromatin regulation through demethylase-independent interactions. Germline loss-of-function variants cause Kabuki syndrome type 2, while somatic alterations occur in multiple cancers.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KDM6A have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TSC1 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• ERCC2: General transcription and DNA repair factor IIH helicase subunit XPD

  Its XPD helicase activity unwinds damaged DNA during nucleotide-excision repair and also supports transcription initiation within TFIIH. Biallelic pathogenic variants cause xeroderma pigmentosum, trichothiodystrophy, or combined DNA-repair syndromes depending on the functional defect.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ERCC2 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• ATM: Serine-protein kinase ATM

  It is activated by DNA double-strand breaks and coordinates checkpoint arrest, repair, and apoptosis through phosphorylation of numerous targets. Biallelic loss causes ataxia-telangiectasia, while heterozygous pathogenic variants increase susceptibility to several cancers.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ATM have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• CDKN2A: Tumor suppressor ARF

  The ARF product of CDKN2A is a tumor-suppressor protein that binds MDM2 and helps preserve p53 activity. By promoting cell-cycle arrest and apoptosis, it provides an important barrier to uncontrolled cell growth from within the nucleolus.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDKN2A have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• CREBBP: CREB-binding protein

  It acetylates histones and integrates signals from many transcription factors to regulate developmental and activity-dependent gene expression. Germline loss-of-function variants cause Rubinstein-Taybi syndrome, while somatic alterations occur in several cancers.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CREBBP have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• EGFR: Epidermal growth factor receptor

  A cell-surface receptor tyrosine kinase that responds to epidermal-growth-factor family ligands. Ligand binding activates phosphorylation cascades that regulate cell growth, survival, and differentiation, which is why EGFR changes are important in cancer biology.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in EGFR have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• EP300: Histone acetyltransferase p300

  It acetylates histones and transcription factors and acts as a central coactivator for developmental and stress-responsive transcription. Germline loss-of-function variants cause Rubinstein-Taybi syndrome type 2, while acquired alterations occur in several cancers.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in EP300 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KMT2C have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KMT2D have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• NF1: Neurofibromin

  It accelerates conversion of active RAS-GTP to inactive RAS-GDP and therefore restrains RAS-MAPK signaling. Loss-of-function variants cause neurofibromatosis type 1 with neurofibromas, pigmentary features, learning difficulties, and increased tumor risk.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NF1 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• STAG2: Cohesin subunit SA-2

  It contributes to cohesin complexes that organize chromosomes, sister-chromatid cohesion, and three-dimensional gene regulation. Somatic loss-of-function mutations are common in myeloid neoplasms, bladder cancer, and other tumors, while germline variants can cause cohesinopathy-associated developmental disorders.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in STAG2 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• TERT: Telomerase reverse transcriptase

  It extends telomeric DNA using an internal RNA template and helps counter progressive chromosome-end shortening in stem and proliferative cells. Loss-of-function variants cause telomere-biology disorders, while promoter activation and increased activity support unlimited proliferation in many cancers.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TERT have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• TP53: Cellular tumor antigen p53

  It coordinates transcriptional responses to DNA damage and other cellular stresses, promoting cell-cycle arrest, senescence, DNA repair, or apoptosis when appropriate. Loss of this tumor-suppressive control is one of the most common events in cancer, while germline pathogenic variants cause Li-Fraumeni syndrome.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TP53 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CTNNB1 have source records linked to Urinary bladder cancer. Association strength is not clinical gene validity.

Weakly linked (only a few uncertain records): FAT2.

ClinVar pathogenic and likely pathogenic variants linked to Urinary bladder cancer

Which prediction tools work for Urinary bladder cancer

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• AlphaMissense: 92 out of 100
• MutPred2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 82 out of 100
• MetaLR: 74 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 72 out of 100

Same protein, different disease

• Lung adenocarcinoma also has ClinVar records linked to ERBB2 variants; they fall mostly in different places as the Urinary bladder cancer variants (3 pathogenic / likely pathogenic).
• FGFR3-related chondrodysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Urinary bladder cancer variants (20 pathogenic / likely pathogenic).
• Hypochondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Urinary bladder cancer variants (15 pathogenic / likely pathogenic).
• Achondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Urinary bladder cancer variants (9 pathogenic / likely pathogenic).
• Thanatophoric dysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Urinary bladder cancer variants (8 pathogenic / likely pathogenic).
• Severe achondroplasia - developmental delay - acanthosis nigricans also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Urinary bladder cancer variants (5 pathogenic / likely pathogenic).
• Costello syndrome also has ClinVar records linked to HRAS variants; they fall partly in the same places as the Urinary bladder cancer variants (15 pathogenic / likely pathogenic).
• RASopathy also has ClinVar records linked to HRAS variants; they fall in the same places as the Urinary bladder cancer variants (6 pathogenic / likely pathogenic).
• Large congenital melanocytic nevus also has ClinVar records linked to HRAS variants; they fall in the same places as the Urinary bladder cancer variants (5 pathogenic / likely pathogenic).
• Epidermal nevus also has ClinVar records linked to HRAS variants; they fall in the same places as the Urinary bladder cancer variants (3 pathogenic / likely pathogenic).
• Pilomatrixoma also has ClinVar records linked to CTNNB1 variants; they fall in the same places as the Urinary bladder cancer variants (8 pathogenic / likely pathogenic).
• Severe intellectual disability-progressive spastic diplegia syndrome also has ClinVar records linked to CTNNB1 variants; they fall mostly in different places as the Urinary bladder cancer variants (5 pathogenic / likely pathogenic).
• Medulloblastoma also has ClinVar records linked to CTNNB1 variants; they fall partly in the same places as the Urinary bladder cancer variants (4 pathogenic / likely pathogenic).
• RASopathy also has ClinVar records linked to KRAS variants; they fall mostly in different places as the Urinary bladder cancer variants (23 pathogenic / likely pathogenic).
• Noonan syndrome also has ClinVar records linked to KRAS variants; they fall mostly in different places as the Urinary bladder cancer variants (16 pathogenic / likely pathogenic).
• Cardiofaciocutaneous syndrome also has ClinVar records linked to KRAS variants; they fall mostly in different places as the Urinary bladder cancer variants (9 pathogenic / likely pathogenic).
• Autoimmune lymphoproliferative syndrome also has ClinVar records linked to KRAS variants; they fall partly in the same places as the Urinary bladder cancer variants (5 pathogenic / likely pathogenic).
• Non-small cell lung carcinoma also has ClinVar records linked to KRAS variants; they fall mostly in different places as the Urinary bladder cancer variants (5 pathogenic / likely pathogenic).

Diseases related to Urinary bladder cancer

• Colorectal cancer, also linked to ARID1A, ATM, CTNNB1, EGFR and 6 more
• Lung adenocarcinoma, also linked to ARID1A, CDKN2A, EGFR, ERBB2 and 4 more
• Non-small cell lung carcinoma, also linked to CDKN2A, EGFR, ERBB2, ERBB3 and 3 more
• Hepatocellular carcinoma, also linked to ARID1A, CDKN2A, CTNNB1, PIK3CA and 3 more
• Head and neck squamous cell carcinoma, also linked to CDKN2A, EGFR, EP300, HRAS and 3 more
• Ovarian cancer, also linked to ATM, CTNNB1, ERBB2, ERCC2 and 2 more
• Gastric cancer, also linked to ATM, ERBB2, KRAS, PIK3CA and 1 more
• Hereditary breast cancer, also linked to ATM, KRAS, PIK3CA and TP53
• Colon carcinoma, also linked to CTNNB1, EP300, FGFR3 and PIK3CA
• Ovarian neoplasm, also linked to CTNNB1, ERBB2, PIK3CA and TP53
• Lung cancer, also linked to EGFR, ERBB2, KRAS and PIK3CA
• Noonan syndrome, also linked to HRAS, KRAS and PIK3CA

Frequently asked questions

Which genes have records linked to Urinary bladder cancer?

This view contains 23 analyzed proteins: ERBB2, ERBB3, FGFR3, HRAS, KRAS and 18 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 19 pathogenic or likely pathogenic variants, 58 variants of uncertain significance and 41 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 176 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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