SOX2 (SRY (sex determining region Y)-box 2)

2011-07-01   Xuefeng Huang , Xu Han , Greg Foltz , Biaoyang Lin 





There is an SOX2OT (SOX2 overlapping transcript) that encodes a non-coding RNA. SOX2OT contains at least five exons and is transcribed into a mRNA of about 3.4 kb from the same strand as SOX2.
Atlas Image
A picture showing the relationship between SOX2 and SOX2OT (adapted from


SOX2 is a single exon gene that encodes a member of the SRY-related HMG-box (SOX) family of transcription factors. The SOX2 single exon contains the 5 untranslated region, CDS region and the 3 untranslated region (427 bp, 954 bp, 1122 bp). The HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species.


The 2503 bases of human SOX2 mRNA contains an open reading frame of 954 bases, resulting in a protein of 318 amino acid residues.


Atlas Image
The 3D structure for the ternary complex of the DNA binding domains of the Oct1 and Sox2 transcription factors with a 19mer oligonucleotide [5- D(Tpgptpcptptptpgptpcpaptpgpcptpapaptpg) -3], left view ( The top chain molecule is the SOX2 DNA binding domain.


The SOX2 protein binds to DNA. The 3D structure for the ternary complex of the DNA binding domains of the Oct1 and Sox2 transcription factors with a 19mer oligonucleotide was solved (Williams et al., 2004;


SOX2 is overexpressed in stem cells and many different kinds of cancer cells, including glioma, breast cancer, colorectal cancer and etc.


Nucleus and cytoplasm.


SOX2 is involved in the regulation of embryonic development and in the determination of cell fate. SOX2 is one of the four transcription factors (SOX2, KLF4, OCT4 and c-Myc), whose over expression can induce pluripotency in both mice and human somatic cells (Takahashi and Yamanaka, 2006; Takahashi et al., 2007). Again, SOX2 is one of the genes in another set of four factors (OCT4, SOX2, NANOG and LIN28) that were able to reprogram human somatic cells to pluripotent stem cells and that exhibit the essential characteristics of embryonic stem (ES) cells (Yu et al., 2007). SOX2 is one of the two factors (SOX2 and OCT4) that were sufficient to generate induced pluripotent stem cells from human cord blood cells (Giorgetti et al., 2010).


So far, twenty SOX genes have been identified in humans and mice and they can be divided into 10 subgroups on the basis of sequence similarity and genomic organization (Bowles et al., 2000; Schepers et al., 2002). SOX genes bind to the minor groove in DNA to control diverse developmental processes (Wegner, 1999). Three genes, SOX1, SOX2 and SOX3, show the closest homology to SRY and share the maximum homology within the HMG domain. These genes also share significant homology outside the HMG box and are highly conserved throughout their evolution.



Mutations in SOX2 cause anophthalmia (no eye), microphthalmia (small eye) and associated ocular developmental anomalies. Fantes identified two nonsense amino-acid changes (S83X and E93X) in the HMG box (high-mobility group DNA-binding domain), which could lead to ablate DNA binding (Fantes et al., 2003). They also observed a recurrent de novo nonsense mutation (529C->T resulting in the amino-acid change Q177X) (Fantes et al., 2003). Additional mutations were later reported for new cases (Bakrania et al., 2007; Pedace et al., 2009; Williamson et al., 2006). SOX2 mutation also caused hearing loss, and brain anomalies (Hagstrom et al., 2005), hypogonadotropic hypogonadism (Sato et al., 2007), ocular coloboma (Wang et al., 2008).

Implicated in

Entity name
SOX2 expression was found to be highly expressed in almost all glioma samples. In agreement with the heterogeneity of the cell population present in each glioma, typically containing cells at various stages of differentiation, SOX2 is expressed in a highly variable percentage of cells, in the range of 6%-80% in different samples (Annovazzi et al., 2011; Gangemi et al., 2009).
Gliomas are the primary cancers derived from glial cells in the brain. It is the most frequent cerebral neoplasias. Astrocytomas are the most common type of gliomas. They are slow-growing, and can be found anywhere in the brain, but most often found in the cerebrum. They can be clinically divided into four grades, with glioblastoma (World Health Organization grade IV) being the most common and aggressive.
Entity name
Lung cancer (small cell lung cancer; lung squamous cell carcinomas)
SOX2 was detected in 50% SCLC cell lines. Hussenet et al. identified SOX2 as an oncogene and likely driver gene of one of the most frequent amplification sites in lung SCC (Hussenet et al., 2010; Sholl et al., 2010a; Sholl et al., 2010b).
Lung cancer results from the uncontrolled growth of abnormal cells in lungs. It is the leading cause of cancer death for both men and women. Close to 90 percent of lung cancers are smoking related.
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that accounts for approximately 20% of all cases of lung cancer. SCLC is a carcinoma of neuroendocrine origin, in contrast to non-SCLC (NSCLC), which is of bronchial epithelial origin.
Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. It is closely correlated with a history of tobacco smoking, more so than most other types of lung carcinoma (Hussenet et al., 2010).
Entity name
Gastric cancer (stomach cancer)
SOX2 expression was significantly down-regulated in gastric carcinoma tissues compared with normal gastric epithelia. SOX2 could induce cell-cycle arrest associated with decreased levels of CCND1 and phosphorylated Rb, and up-regulated p27Kip1 level (Otsubo et al., 2008).
Gastric cancer, commonly referred to as stomach cancer, forms in tissues that line the stomach. Adenocarcinomas is the most comnon type (90-95%),but there are other types of stomach cancer including squamous cell carcinoma, lymphoma, and stromal tumors. Gastric cancer is the second most frequent cause of death from cancer in both sexes in the world.
Entity name
Breast cancer
SOX2 nuclear protein level was highly associated with basal-like phenotype in human breast cancer. Knockdown of SOX2 could inhibit tumorgenesis in vitro and in vivo (Chen et al., 2008).
Breast cancer forms in the tissues of one or both breasts. It primarily affects women, but can also occur in children and men. It can be a highly curable disease if detected and treated early.
Entity name
Colorectal cancer
SOX2 expression in colorectal cancer tissues was found overexpressed in the cancerous tissues compared to normal adjacent tissues. Knockdown of SOX2 in colorectal cancer cells decreased their growth rates in vitro cell line and in vivo in xenograft models (Fang et al., 2010).
Colorectal cancer is the second most common malignancy in cancer patients and cause of cancer-related mortality. Colorectal cancers develop slowly over many years, initially as a polyp in the inner lining of the colon or rectum, which may progress into cancerous lesions called adenocarcinomas. More than 95 percent of colorectal cancers are adenocarcinomas. Removing the polyp early may prevent progession to cancer. Other less common types of colorectal cancers include carcinoid tumors, gastrointestinal stromal tumors and lymphomas.


Pubmed IDLast YearTitleAuthors
215188202011SOX2 expression and amplification in gliomas and glioma cell lines.Annovazzi L et al
175221442007SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions.Bakrania P et al
110717522000Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators.Bowles J et al
184566562008The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer.Chen Y et al
207267972010ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers.Fang X et al
126125842003Mutations in SOX2 cause anophthalmia.Fantes J et al
189486462009SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity.Gangemi RM et al
203607732010Generation of induced pluripotent stem cells from human cord blood cells with only two factors: Oct4 and Sox2.Giorgetti A et al
161456812005SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies.Hagstrom SA et al
201264102010SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.Hussenet T et al
182684982008SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis.Otsubo T et al
192547842009A novel heterozygous SOX2 mutation causing anophthalmia/microphthalmia with genital anomalies.Pedace L et al
172874052007Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2.Sato N et al
121948482002Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families.Schepers GE et al
206316052010Sox2 protein expression is an independent poor prognostic indicator in stage I lung adenocarcinoma.Sholl LM et al
196617862010Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas.Sholl LM et al
180354082007Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Takahashi K et al
184747842008Novel SOX2 mutation associated with ocular coloboma in a Chinese family.Wang P et al
100378001999From head to toes: the multiple facets of Sox proteins.Wegner M et al
145598932004Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex.Williams DC Jr et al
165433592006Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome.Williamson KA et al
180294522007Induced pluripotent stem cell lines derived from human somatic cells.Yu J et al

Other Information

Locus ID:

NCBI: 6657
MIM: 184429
HGNC: 11195
Ensembl: ENSG00000181449


dbSNP: 6657
ClinVar: 6657
TCGA: ENSG00000181449


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Signal TransductionREACTOMER-HSA-162582
Signaling by WntREACTOMER-HSA-195721
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Deactivation of the beta-catenin transactivating complexREACTOMER-HSA-3769402
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of pluripotent stem cellsREACTOMER-HSA-452723
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferationREACTOMER-HSA-2892247
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiationREACTOMER-HSA-2892245
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
161537022005Core transcriptional regulatory circuitry in human embryonic stem cells.1612
181571152008Reprogramming of human somatic cells to pluripotency with defined factors.1046
194096072009MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.447
198019782009SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.391
229411892012Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.334
235419212013Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.266
189486462009SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity.238
187109382008Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells.225
218223032012Sox2 expression in breast tumours and activation in breast cancer stem cells.201
280597682017SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer.200


Xuefeng Huang ; Xu Han ; Greg Foltz ; Biaoyang Lin

SOX2 (SRY (sex determining region Y)-box 2)

Atlas Genet Cytogenet Oncol Haematol. 2011-07-01

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