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SPOP

Chr 17q21.33

speckle type BTB/POZ protein

Aliases:
TEF2, BTBD32
MANE:
ENST00000504102.6
OMIM: 602650 ↗NCBI: 8405 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Intellectual disability

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Fetal anomalies

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Familial prostate cancer

    BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

  • neurodevelopmental disorder with microcephaly and dysmorphic facies

    0.70

  • neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies

    0.69

  • prostate adenocarcinoma

    0.67

  • neurodegenerative disease

    0.46

  • prostate carcinoma

    0.40

  • endometrial cancer

    0.39

  • carcinoma of liver and intrahepatic biliary tract

    0.37

  • bile duct carcinoma

    0.37

  • endometrial clear cell adenocarcinoma

    0.37

  • nodular malignant melanoma

    0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Speckle-type POZ protein

Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420). Plays an essential role for proper translation, but not for their degradation, of critical DNA replication licensing factors CDT1 and CDC6, thereby participating in DNA synthesis and cell proliferation (PubMed:36791496). Regulates interferon regulatory factor 1/IRF1 proteasomal turnover by targeting S/T-rich degrons in IRF1 (PubMed:37622993). Facilitates the lysosome-dependent degradation of enterovirus EV71 protease 2A by inducing its 'Lys-48'-linked polyubiquitination, which ultimately restricts EV71 replication (PubMed:37796126). Acts as an antiviral factor also against hepatitis B virus/HBV by promoting ubiquitination and subsequent degradation of HNF1A (PubMed:38018242). In turn, inhibits HBV transcription and replication by preventing HNF1A stimulating activity of HBV preS1 promoter and enhancer II (PubMed:38018242). Involved in ubiquitination of BRDT and promotes its degradation, thereby regulates histone removal in early condensing spermatids prior to histone-to-protamine exchange (By similarity)

Diseases associated with SPOP

Curated MONDO disease pages that list SPOP among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.