Affinage

SOX30

Transcription factor SOX-30 · UniProt O94993

Length
753 aa
Mass
81.9 kDa
Annotated
2026-06-10
30 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX30 is an HMG-box transcription factor that functions as a master regulator of postmeiotic spermatogenesis and, in somatic tissues, as a tumor suppressor (PMID:29247201, PMID:29866902, PMID:29739711). In the testis, SOX30 is essential for the transition through round spermatid differentiation: Sox30-null males are completely sterile, arresting at step 3 spermiogenesis with aberrant acrosome and axoneme development and multinucleated symplasts, while females are unaffected (PMID:29247201). SOX30 establishes a core postmeiotic gene program beginning in late meiosis, binding specific DNA sequences genome-wide to drive expression of spermatid genes such as Tnp1, Hils1, Ccdc54 and Tsks (PMID:29866902), and it directly activates the synaptonemal complex genes SYCE1 and SYCE2 to support central-element assembly, DNA double-strand break repair and crossover formation (PMID:41467312). SOX30 expression is itself controlled at multiple levels: it is restricted to testis by CpG-island promoter methylation (PMID:24810894), induced by retinoic acid and MYBL1, and reinforced by direct autoregulation of its own promoter (PMID:29848638). Promoter hypermethylation silences SOX30 in non-obstructive azoospermia, and adeno-associated-virus re-expression of Sox30 in null adult mice restores spermatogenesis and fertility, establishing a causal link to male infertility (PMID:31835093); a human stop-gained mutation (Arg478*) abolishes association with HDAC3 and HMG-domain missense mutations impair DNA binding (PMID:41269228). In cancer, SOX30 acts as a tumor suppressor through two principal axes: it directly binds and transactivates the p53 promoter (PMID:25435374), and it antagonizes Wnt/β-catenin signaling both by transcriptionally repressing β-catenin and by binding β-catenin protein through its amino-terminus to compete with TCF (PMID:29739711). SOX30 is post-transcriptionally repressed by microRNAs including miR-645 and miR-653-5p in hepatocellular, prostate and other cancers (PMID:30312695, PMID:31889959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2014 Medium

    Established that SOX30 tissue-restricted expression is set epigenetically, explaining why this factor is testis-specific.

    Evidence Methylation-specific PCR, bisulfite sequencing and 5-aza-dC demethylation rescue across mouse tissues and cell lines

    PMID:24810894

    Open questions at the time
    • Does not identify the demethylating machinery in testis
    • Does not link methylation state to a downstream transcriptional program
  2. 2014 Medium

    Defined SOX30 as a direct transcriptional activator of p53, providing the first molecular mechanism for its tumor-suppressor activity.

    Evidence ChIP at the p53 promoter, ectopic expression/knockdown with proliferation and apoptosis readouts, and in vivo tumor formation in lung cancer cells

    PMID:25435374

    Open questions at the time
    • Single lung-cancer context
    • Does not address whether tumor suppression requires p53 in all cell types
  3. 2017 High

    Demonstrated by clean knockout that SOX30 is absolutely required for the round spermatid stage, defining its essential developmental role.

    Evidence Sox30 knockout mouse with histological staging of spermatogenesis

    PMID:29247201

    Open questions at the time
    • Did not identify direct target genes at this stage
    • Mechanism of symplast formation unresolved
  4. 2018 High

    Resolved the genome-wide targets of SOX30, showing it directly drives a defined postmeiotic gene program initiated in late meiosis.

    Evidence ChIP-seq plus stage-specific transcriptomics in Sox30 mutant mouse spermatogenic cells

    PMID:29866902

    Open questions at the time
    • Co-factors directing SOX30 occupancy not defined
    • Consensus binding motif vs. cancer ACAAT/CACTTTG motifs not reconciled
  5. 2018 High

    Showed SOX30 antagonizes Wnt/β-catenin signaling through dual transcriptional and protein-level mechanisms, mapping the responsible domains.

    Evidence Reciprocal Co-IP, ChIP, TOP/FOP reporter, domain-deletion mutants, and in vivo metastasis/knockout models in lung cancer

    PMID:29739711

    Open questions at the time
    • Structural basis of β-catenin/TCF competition not determined
    • Relative contribution of repression vs. sequestration in vivo unquantified
  6. 2018 Medium

    Established autoregulation and upstream control of SOX30 transcription, embedding it in the retinoic acid/MYBL1 meiotic entry circuit.

    Evidence Promoter reporter assays, ChIP for self-binding, and retinoic acid treatment in Sox30 knockout mice

    PMID:29848638

    Open questions at the time
    • MYBL1 regulation inferred from knockout context rather than direct binding
    • Quantitative role of autoregulation in expression timing unclear
  7. 2018 Medium

    Extended SOX30 tumor suppression to direct activation of desmosomal genes, linking it to cell-adhesion control of Wnt and ERK signaling.

    Evidence ChIP at the ACAAT motif of DSP/JUP/DSC3 promoters, functional assays, and SOX30-knockout carcinogenesis model in lung adenocarcinoma

    PMID:29855376

    Open questions at the time
    • Single lab
    • Mechanistic link between desmosomal genes and signaling not fully dissected
  8. 2018 Medium

    Identified miR-645 as an upstream repressor of SOX30, extending its p53-activating tumor-suppressor axis to hepatocellular carcinoma.

    Evidence Luciferase 3'-UTR reporter, gain/loss-of-function, and ChIP for p53 promoter binding

    PMID:30312695

    Open questions at the time
    • Single context
    • Does not establish in vivo relevance of the miRNA axis
  9. 2019 High

    Provided causal in vivo proof that SOX30 silencing underlies human azoospermia and that restoring it rescues fertility.

    Evidence Genome-wide methylation profiling of NOA testes plus AAV-mediated Sox30 re-expression in null adult mice with offspring analysis

    PMID:31835093

    Open questions at the time
    • Frequency of SOX30 methylation across NOA cohorts not established
    • Therapeutic translatability untested in human tissue
  10. 2019 Medium

    Confirmed conserved transcriptional control of SOX30 in spermatogenesis by Dmrt1 in a teleost, and added miR-653-5p as another repressor in cancer.

    Evidence EMSA/ChIP-PCR/reporter for Dmrt1 binding in Nile tilapia; dual-luciferase and functional assays for miR-653-5p in prostate cancer

    PMID:31690021 PMID:31889959

    Open questions at the time
    • Cross-species conservation of Dmrt1 regulation in mammals untested
    • miR-653-5p axis shown in single cell context
  11. 2020 Medium

    Placed SOX30 genetically upstream of β-catenin in leukemia, generalizing its Wnt-suppressor role beyond solid tumors.

    Evidence Overexpression/knockdown, β-catenin rescue epistasis, and xenografts in acute myeloid leukemia cells

    PMID:32334007

    Open questions at the time
    • Direct binding to β-catenin promoter in AML not shown
    • Single lab
  12. 2021 Medium

    Demonstrated conserved direct target-gene activation by Sox30 driving spermiogenesis in a teleost model.

    Evidence CRISPR/Cas9 knockout, ChIP-seq/ChIP-PCR and reporter assays for ift140 and ptprb in Nile tilapia

    PMID:34801758

    Open questions at the time
    • Mammalian orthology of ift140/ptprb regulation untested
    • Subfertility vs. mouse sterility difference unexplained
  13. 2025 High

    Revealed an earlier meiotic role for SOX30 in synaptonemal complex assembly and recombination, predating its postmeiotic function.

    Evidence Sox30-knockout chromosome spreads, ChIP at SYCE1/SYCE2 promoters, immunofluorescence for SC/recombination markers and re-expression rescue

    PMID:41467312

    Open questions at the time
    • How SOX30 coordinates meiotic and postmeiotic programs unclear
    • Direct vs. indirect effect on RAD51/RPA2 persistence not fully separated
  14. 2026 Medium

    Connected human SOX30 coding mutations to infertility and mapped the functional consequences of HMG-domain and C-terminal lesions.

    Evidence NOA patient genetic screening, in vitro HDAC3-interaction and DNA-binding assays, and a Sox30 P382S knock-in mouse

    PMID:41269228

    Open questions at the time
    • Functional role of the SOX30–HDAC3 interaction in vivo undefined
    • Genotype–phenotype correlation in larger cohorts lacking
  15. 2026 Medium

    Identified SOX30 as a node linking environmental toxicant exposure to homologous-recombination repair failure in spermatocytes.

    Evidence PFOS treatment of GC2 cells with SOX30 overexpression rescue and RPA2/RAD51 readouts plus chromosome spreading

    PMID:41905031

    Open questions at the time
    • In vivo PFOS-SOX30 axis not tested
    • Mechanism of PFOS-induced SOX30 suppression unknown
  16. 2026 Medium

    Extended SOX30 tumor suppression to an autophagy-dependent rather than apoptotic mechanism in ovarian cancer.

    Evidence Proliferation/colony/flow assays, autophagy confocal imaging, co-expression analysis and xenografts

    PMID:41566108

    Open questions at the time
    • Direct autophagy gene targets not identified
    • Relationship to p53/Wnt axes unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SOX30 partitions between its meiotic, postmeiotic and somatic tumor-suppressor programs through context-specific cofactors and binding motifs remains unresolved.
  • No structural model of SOX30 on DNA or with β-catenin/HDAC3
  • Cofactors directing tissue-specific occupancy unknown
  • Reconciliation of distinct binding motifs (CACTTTG, ACAAT, SC promoters) lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
CTNNB1HDAC3TCF

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 SOX30 directly binds to the CACTTTG sequence (+115 to +121) of the p53 promoter region and transcriptionally activates p53 expression, mediating tumor suppression in lung cancer cells. Chromatin immunoprecipitation (ChIP) assay, ectopic expression/knockdown with proliferation and apoptosis readouts, in vivo tumor formation assay Oncogene Medium 25435374
2017 SOX30 is required for the post-meiotic round spermatid stage of spermatogenesis in male mice; Sox30-null males are completely sterile with arrest at step 3 spermiogenesis, aberrant acrosome and axoneme development, and formation of multinucleated symplasts, while females are fertile. Sox30 knockout mouse model, histological analysis, assessment of spermatogenic stages Scientific reports High 29247201
2018 SOX30 inhibits tumor metastasis in lung cancer by two mechanisms: (1) directly transcriptionally repressing β-catenin expression, and (2) binding β-catenin protein via its amino-terminus to compete with TCF for β-catenin binding, with the carboxyl-terminus required for attenuating β-catenin transcriptional activity. Co-immunoprecipitation, ChIP assay, TOP/FOP flash reporter assay, domain deletion mutants, in vitro migration/invasion assays, in vivo metastasis models, Sox30 knockout mice EBioMedicine High 29739711
2018 SOX30 controls a core postmeiotic gene expression program in mouse testes, initiating as early as late meiotic cell stages; ChIP-seq shows SOX30 binds specific DNA sequences and its genomic occupancy correlates positively with expression of postmeiotic genes including Tnp1, Hils1, Ccdc54, and Tsks. Sox30 mutant mice, transcriptome analysis of stage-specific spermatogenic cells, ChIP-seq Development (Cambridge, England) High 29866902
2018 SOX30 transcription in mouse testes is regulated by retinoic acid and by the transcription factor MYBL1 before and during meiosis; SOX30 protein also binds the proximal promoter of its own gene and activates its own transcription (autoregulation). Sox30 knockout mice, retinoic acid treatment experiments, promoter reporter assays, ChIP Development (Cambridge, England) Medium 29848638
2018 SOX30 acts as a transcriptional regulator of desmosomal genes (DSP, JUP, DSC3) in lung adenocarcinoma by directly binding to the ACAAT motif in desmosomal gene promoter regions, thereby activating their transcription and inhibiting downstream Wnt and ERK signaling. ChIP assay, promoter binding analysis, miRNA knockdown of desmosomal genes, in vitro proliferation/migration/invasion assays, in vivo nude mouse model, SOX30-knockout carcinogenesis model, TOP/FOP flash reporter assay Journal of experimental & clinical cancer research Medium 29855376
2018 miR-645 directly binds to the 3'-UTR of SOX30 and post-transcriptionally represses SOX30 expression in hepatocellular carcinoma cells; SOX30 in turn activates p53 transcription by directly binding its promoter. Luciferase 3'-UTR reporter assay, gain- and loss-of-function experiments, ChIP for p53 promoter binding International journal of biological macromolecules Medium 30312695
2019 SOX30 hypermethylation at its promoter directly causes silencing of SOX30 expression in non-obstructive azoospermia (NOA) patient testicular tissues; re-expression of Sox30 in Sox30-null adult mice reverses pathological testicular damage, restores spermatogenesis, and produces spermatozoa capable of initiating pregnancy. Genome-wide methylation profiling, Sox30-null mouse model, adeno-associated virus-mediated re-expression in adult null mice, fertility testing, offspring analysis Molecular therapy. Nucleic acids High 31835093
2019 SOX30 is a target gene of miR-653-5p; miR-653-5p overexpression decreases SOX30 expression, and SOX30 overexpression or miR-653-5p inhibition reduces β-catenin expression and suppresses Wnt/β-catenin signaling in prostate cancer cells. Dual-luciferase reporter assay for miRNA-mRNA interaction, western blot, proliferation/invasion assays, siRNA knockdown Cellular & molecular biology letters Medium 31889959
2019 Dmrt1 positively regulates transcription of the Sox30 gene in Nile tilapia by directly binding to a specific cis-regulatory element (CRE) within the Sox30 promoter. Dual-luciferase reporter assay, ChIP-PCR, electrophoretic mobility shift assay (EMSA), Dmrt1 knockdown experiments International journal of molecular sciences Medium 31690021
2020 SOX30 overexpression in acute myeloid leukemia cells markedly decreases β-catenin expression, leading to inactivation of the Wnt/β-catenin pathway; restoration of β-catenin partially reverses SOX30-mediated tumor suppression, placing SOX30 upstream of β-catenin in this pathway. SOX30 overexpression/siRNA knockdown, western blot for β-catenin, β-catenin rescue experiments, xenograft mouse model Molecular and cellular probes Medium 32334007
2021 Sox30 in Nile tilapia localizes to spermatocytes and spermatids in the testis and directly regulates transcription of spermiogenesis-related genes ift140 and ptprb by binding to their promoters; CRISPR/Cas9-mediated sox30 mutation causes abnormal spermiogenesis, reduced sperm motility, and male subfertility. CRISPR/Cas9 knockout, ChIP-seq, ChIP-PCR, luciferase reporter assay, comparative transcriptome analysis Journal of genetics and genomics Medium 34801758
2025 SOX30 directly binds to SYCE1 and SYCE2 promoters to activate their transcription, regulating synaptonemal complex (SC) assembly; Sox30 knockout mice show defects in SC central element distribution (SYCE1, SYCE2, TEX12), impaired DNA double-strand break repair, persistence of RAD51 and RPA2 in late spermatocytes, and reduced crossover formation. Sox30-knockout mice, chromosome spreading, ChIP for SYCE1/SYCE2 promoters, immunofluorescence for SC components and recombination proteins, transcriptome co-expression analysis, Sox30 re-expression rescue Cell proliferation High 41467312
2026 A human SOX30 stop-gained mutation (Arg478*) produces a C-terminal truncated protein with dramatically reduced association with HDAC3; missense mutations in the HMG domain reduce SOX30 DNA-binding ability; a P353S missense mutation modeled in mice (P382S knock-in) causes defects in late spermatocyte stages and reduces mature sperm without complete sterility. Genetic screening of NOA patients, in vitro functional assays for protein-protein interaction with HDAC3, DNA-binding assays, Sox30P382S knock-in mouse model Biology of reproduction Medium 41269228
2026 PFOS exposure suppresses SOX30 expression in spermatocytes, leading to downregulation of its downstream targets RPA2 and RAD51 (key homologous recombination repair proteins), resulting in unrepaired DNA double-strand breaks and spermatocyte apoptosis; overexpression of SOX30 in PFOS-exposed GC2 cells restores RPA2/RAD51 expression and rescues DSB repair capacity. In vitro PFOS treatment of GC2 spermatocyte cells, SOX30 overexpression rescue, western blot for RPA2/RAD51, chromosome spreading with high-resolution microscopy Ecotoxicology and environmental safety Medium 41905031
2026 SOX30 suppresses ovarian cancer cell proliferation primarily through an autophagy-mediated mechanism rather than apoptosis; SOX30 overexpression induces marked autophagy and co-expression analysis links SOX30 to key autophagy-related genes. MTS assay, colony formation assay, flow cytometry, western blotting, confocal microscopy for autophagy, xenograft model, co-expression analysis Discover oncology Medium 41566108
2014 SOX30 expression in mouse testis is regulated by DNA methylation status at its CpG island promoter; Sox30 is hypo-methylated in testis (where it is expressed) and hypermethylated in other tissues (where it is silenced); demethylation with 5-aza-dC restores Sox30 expression in GC2, TM3, and TM4 cell lines. Methylation-specific PCR, bisulfite sequencing, 5-aza-dC demethylation treatment, RT-PCR expression analysis across tissues PloS one Medium 24810894

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer. Oncogene 64 25435374
2017 SOX30 is required for male fertility in mice. Scientific reports 55 29247201
2018 SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via Transcriptional and Posttranslational Regulation of β-Catenin in Lung Cancer. EBioMedicine 52 29739711
2018 Sox30 initiates transcription of haploid genes during late meiosis and spermiogenesis in mouse testes. Development (Cambridge, England) 48 29866902
2014 Epigenetic regulation of sox30 is associated with testis development in mice. PloS one 45 24810894
2018 The transcription factor SOX30 is a key regulator of mouse spermiogenesis. Development (Cambridge, England) 43 29848638
2010 Characterization, phylogeny, alternative splicing and expression of Sox30 gene. BMC molecular biology 42 21143990
2019 Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia. Molecular therapy. Nucleic acids 30 31835093
2019 SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/β-catenin signaling. Cellular & molecular biology letters 30 31889959
2018 MicroRNA-645 represses hepatocellular carcinoma progression by inhibiting SOX30-mediated p53 transcriptional activation. International journal of biological macromolecules 27 30312695
2015 High expression of SOX30 is associated with favorable survival in human lung adenocarcinoma. Scientific reports 27 26330328
2018 SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma. Journal of experimental & clinical cancer research : CR 26 29855376
2021 The transcription factor Sox30 is involved in Nile tilapia spermatogenesis. Journal of genetics and genomics = Yi chuan xue bao 14 34801758
1999 sox30: a novel zebrafish sox gene expressed in a restricted manner at the midbrain-hindbrain boundary during neurogenesis. Development genes and evolution 12 10370117
2020 Dnajb8, a target gene of SOX30, is dispensable for male fertility in mice. PeerJ 11 33391882
2020 Role of sox30 in regulating testicular steroidogenesis of common carp. The Journal of steroid biochemistry and molecular biology 10 33065277
2019 SOX30 methylation correlates with disease progression in patients with chronic myeloid leukemia. OncoTargets and therapy 10 31417278
2019 Transcription of the Sox30 Gene Is Positively Regulated by Dmrt1 in Nile Tilapia. International journal of molecular sciences 10 31690021
2018 Different expressions of miR-125b and SOX30 in malignant lymphomas and their significance. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 9 30358229
2020 SOX30 confers a tumor suppressive effect in acute myeloid leukemia through inactivation of Wnt/β-catenin signaling. Molecular and cellular probes 7 32334007
2025 Single-cell RNA-seq and pathological phenotype reveal the functional atlas and precise roles of Sox30 in testicular cell development and differentiation. Cell death & disease 6 39971903
2000 HMG-box sequences from microbats homologous to the human SOX30 HMG-box. Genetica 4 11678506
2024 Multifaceted roles and functions of SOX30 in human cancer. Cancer innovation 3 38946929
2022 SOX30 Overexpression Reflects Tumor Invasive Degree, Lymph Node Metastasis and Predicts Better Survival in Colorectal Cancer Patients: A Long-Term Follow-Up Cohort Study. Frontiers in surgery 1 35836594
2026 Mutations of SOX30 are identified in azoospermic human patients and reduce sperm in mice†. Biology of reproduction 0 41269228
2026 SOX30 is a diagnostic biomarker that suppresses ovarian cancer progression through an autophagy mediated mechanism. Discover oncology 0 41566108
2026 PFOS-mediated suppression of SOX30 impairs DNA double-strand break repair leading to male reproductive dysfunction. Ecotoxicology and environmental safety 0 41905031
2025 Molecular Characterization and Expression Patterns of Sox3 and Sox30 Genes and Response to Exogenous Hormones in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis). Genes 0 41300700
2025 SOX18 and SOX30 in NSCLC: The Epigenetic Landscape of Methylation, miRNA Regulation, and Network Crosstalk in Tumor Progression. International journal of molecular sciences 0 41373817
2025 SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis. Cell proliferation 0 41467312

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