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Atlas / Gene / SOX21

SOX21

gene
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Also known as SOX25

Summary

SOX21 (SRY-box transcription factor 21, HGNC:11197) is a protein-coding gene on chromosome 13q32.1, encoding Transcription factor SOX-21 (Q9Y651). May play a role as an activator of transcription of OPRM1.

SRY-related HMG-box (SOX) genes encode a family of DNA-binding proteins containing a 79-amino acid HMG (high mobility group) domain that shares at least 50% sequence identity with the DNA-binding HMG box of the SRY protein (MIM 480000). SOX proteins are divided into 6 subgroups based on sequence similarity within and outside of the HMG domain. For additional background information on SOX genes, see SOX1 (MIM 602148).

Source: NCBI Gene 11166 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 29 total — 1 pathogenic
  • Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
  • MANE Select transcript: NM_007084

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11197
Approved symbolSOX21
NameSRY-box transcription factor 21
Location13q32.1
Locus typegene with protein product
StatusApproved
AliasesSOX25
Ensembl geneENSG00000125285
Ensembl biotypeprotein_coding
OMIM604974
Entrez11166

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376945

RefSeq mRNA: 1 — MANE Select: NM_007084 NM_007084

CCDS: CCDS9473

Canonical transcript exons

ENST00000376945 — 1 exons

ExonStartEnd
ENSE000014722099470962294712545

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 92.41.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4402 / max 192.8840, expressed in 302 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
1378561.4938249
1378550.4789143
1378570.2645133
1378580.088831
1378530.053620
1378590.032718
1378540.027812

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
ventricular zoneUBERON:000305392.41gold quality
ganglionic eminenceUBERON:000402385.76gold quality
skin of legUBERON:000151180.62gold quality
skin of abdomenUBERON:000141679.54gold quality
amygdalaUBERON:000187678.39gold quality
caudate nucleusUBERON:000187376.78gold quality
esophagus mucosaUBERON:000246975.78gold quality
putamenUBERON:000187475.53gold quality
zone of skinUBERON:000001475.14gold quality
nucleus accumbensUBERON:000188274.93gold quality
cingulate cortexUBERON:000302774.76gold quality
anterior cingulate cortexUBERON:000983574.57gold quality
right frontal lobeUBERON:000281074.44gold quality
olfactory segment of nasal mucosaUBERON:000538674.42gold quality
lower esophagus mucosaUBERON:003583473.54gold quality
Brodmann (1909) area 9UBERON:001354073.38gold quality
prefrontal cortexUBERON:000045172.40gold quality
embryoUBERON:000092271.42gold quality
hypothalamusUBERON:000189870.85gold quality
dorsolateral prefrontal cortexUBERON:000983469.41gold quality
C1 segment of cervical spinal cordUBERON:000646968.68gold quality
neocortexUBERON:000195068.04gold quality
body of stomachUBERON:000116167.64gold quality
telencephalonUBERON:000189367.38gold quality
frontal cortexUBERON:000187066.74gold quality
stomachUBERON:000094565.99gold quality
spinal cordUBERON:000224065.98gold quality
substantia nigraUBERON:000203865.43gold quality
cerebral cortexUBERON:000095665.31gold quality
forebrainUBERON:000189064.96gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no2.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

TargetRegulation
HES5
OPRM1Activation

JASPAR motifs

MotifNameFamily
MA0866.1SOX21SOX-related factors

JASPAR matrix evidence (PMIDs): PMID:12920151

Upstream regulators (CollecTRI, top): SOX2

miRNA regulators (miRDB)

85 targeting SOX21, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-3646100.0073.565283
HSA-MIR-5692A100.0074.406850
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-656-3P100.0072.152788
HSA-MIR-4789-3P99.9970.752484
HSA-MIR-366299.9973.825684
HSA-MIR-428299.9975.366408
HSA-MIR-548AW99.9972.573559
HSA-MIR-1213699.9872.815713
HSA-MIR-806899.9873.852376
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-426799.9666.532368
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-450B-5P99.9271.483175
HSA-MIR-6508-5P99.9270.672465
HSA-MIR-806799.8669.592260
HSA-MIR-469899.8471.414303
HSA-MIR-576-5P99.8470.462582
HSA-MIR-442099.8270.081624
HSA-MIR-181B-2-3P99.8170.061646

Literature-anchored findings (GeneRIF, showing 11)

  • suggest that Sox21 can negatively regulate Sox2 in glioma. Our findings imply that Sox2 and Sox21 may be interesting targets for the development of novel glioma therapy (PMID:20824710)
  • Tumors originating from glioma cells with an induced expression of Sox21 exhibited an increased formation of Sox2:Sox21 complexes and an upregulation of S100beta, CNPase and Tuj1 (PMID:23463365)
  • The tumorigenic effect of lncRNA SOX21-AS1 in CRC cells via targeting miR-145/MYO6, providing a novel insight for CRC carcinogenesis. (PMID:29217166)
  • SOX21-AS1 could be a potential prognostic biomarker . (PMID:29772433)
  • SOX21-AS1 functions as oncogenic lncRNA in nephroblastoma. (PMID:30992391)
  • these results unveil the unknown role of SOX21 and shed light on how a transcriptional factor modulates early neural regionalization through crosstalk with a key component of Wnt signaling. (PMID:31761677)
  • High potential of SOX21 gene promoter methylation as an epigenetic biomarker for early detection of colorectal cancer. (PMID:32445320)
  • Quantitative detection of SRY-Box 21 (SOX21) gene promoter methylation as a stool-based noninvasive biomarker for early diagnosis of colorectal cancer by MethyLight method. (PMID:33402569)
  • SOX21 modulates SOX2-initiated differentiation of epithelial cells in the extrapulmonary airways. (PMID:34286693)
  • SOX21-AS1 activated by STAT6 promotes pancreatic cancer progression via up-regulation of SOX21. (PMID:36335356)
  • SOX2 and SOX21 in Lung Epithelial Differentiation and Repair. (PMID:36361852)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriosox21bENSDARG00000008540
mus_musculusSox21ENSMUSG00000061517
rattus_norvegicusSox21ENSRNOG00000063983
drosophila_melanogasterSox21bFBGN0042630
caenorhabditis_elegansWBGENE00015716

Paralogs (20): SOX8 (ENSG00000005513), SOX30 (ENSG00000039600), SOX10 (ENSG00000100146), SOX6 (ENSG00000110693), SOX4 (ENSG00000124766), SOX9 (ENSG00000125398), SOX15 (ENSG00000129194), SOX5 (ENSG00000134532), SOX3 (ENSG00000134595), SOX13 (ENSG00000143842), SOX17 (ENSG00000164736), SOX14 (ENSG00000168875), SOX7 (ENSG00000171056), SOX11 (ENSG00000176887), SOX12 (ENSG00000177732), CFAP65 (ENSG00000181378), SOX2 (ENSG00000181449), SOX1 (ENSG00000182968), SRY (ENSG00000184895), SOX18 (ENSG00000203883)

Protein

Protein identifiers

Transcription factor SOX-21 — Q9Y651 (reviewed: Q9Y651)

Alternative names: SOX-A

All UniProt accessions (1): Q9Y651

UniProt curated annotations — full annotation on UniProt →

Function. May play a role as an activator of transcription of OPRM1. Overexpression of SOX21 can up-regulate the OPRM1 distal promoter activity in mor-expressing neuronal cells. May play a role in ameloblast differentiation.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_009015* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR009071HMG_box_domDomain
IPR022097SOX_famFamily
IPR036910HMG_box_dom_sfHomologous_superfamily
IPR050140SRY-related_HMG-box_TF-likeFamily

Pfam: PF00505, PF12336

UniProt features (5 total): sequence conflict 2, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9Y651-F165.950.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NEUROGENESIS, AAAYRNCTG_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_DN, MODULE_99, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, AACTTT_UNKNOWN, GOBP_STEM_CELL_DIFFERENTIATION, DBP_Q6, GOBP_SKIN_DEVELOPMENT, SHEPARD_BMYB_TARGETS

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), hair follicle development (GO:0001942), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), neuron differentiation (GO:0030182), positive regulation of transcription by RNA polymerase II (GO:0045944), stem cell differentiation (GO:0048863), developmental process (GO:0032502), hair cycle (GO:0042633), skin development (GO:0043588)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of transcription by RNA polymerase II3
transcription by RNA polymerase II3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
regulation of DNA-templated transcription2
animal organ development2
cell differentiation2
negative regulation of DNA-templated transcription1
hair cycle process1
anatomical structure development1
skin epidermis development1
DNA-templated transcription1
regulation of gene expression1
regulation of RNA biosynthetic process1
central nervous system development1
head development1
generation of neurons1
positive regulation of DNA-templated transcription1
biological_process1
molting cycle1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription activator activity1
positive regulation of transcription by RNA polymerase II1
nucleic acid binding1
transcription cis-regulatory region binding1
transcription regulator activity1
chromosome1
cellular anatomical structure1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

4 interactions, top by confidence:

ABTypeScore
SOX2PDLIM1psi-mi:“MI:0914”(association)0.530
SOX21EWSR1psi-mi:“MI:0914”(association)0.350
SOX7NFIBpsi-mi:“MI:2364”(proximity)0.270

BioGRID (16): SOX21 (Affinity Capture-MS), SOX21 (Affinity Capture-MS), SOX21 (Affinity Capture-MS), SOX21 (Affinity Capture-MS), SOX21 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), EWSR1 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), MINA (Affinity Capture-MS), SOX21 (Affinity Capture-MS), SOX21 (Affinity Capture-MS), SOX21 (Negative Genetic), SOX21 (Affinity Capture-RNA), SOX21 (Proximity Label-MS)

ESM2 similar proteins: A4QNG3, A8WWH5, B0ZTE1, B0ZTE2, O09100, O42569, O60481, O73689, O95416, P23769, P23770, P23824, P41225, P43694, P46152, P46684, P47792, P48433, P53784, P55863, P61259, Q04892, Q08369, Q0Q0E4, Q12946, Q15915, Q24648, Q28BS5, Q2Z1R2, Q32PP9, Q61080, Q62521, Q68FA4, Q6DGL6, Q6DJQ6, Q6EJB7, Q6NVN0, Q6RVD7, Q7SZS1, Q811W0

Diamond homologs: A2TED3, A4QNG3, B0ZTE1, B0ZTE2, O00570, O42569, O57401, O60248, O95416, P36389, P36390, P36393, P36395, P36396, P41225, P43267, P47792, P48046, P48430, P48431, P48432, P48433, P51501, P53783, P53784, P54231, P55863, P61259, Q04892, Q05066, Q20201, Q21305, Q24533, Q28447, Q28778, Q28783, Q28798, Q2PG84, Q2Z1R2, Q32PP9

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — PRAD.

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance26
Likely benign1
Benign1

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
2684703GRCh37/hg19 13q21.2-34(chr13:61534068-115107733)x3Pathogenic

SpliceAI

81 predictions. Top by Δscore:

VariantEffectΔscore
13:94710628:ATCT:Aacceptor_gain0.7600
13:94710629:TCTGC:Tacceptor_gain0.6700
13:94710652:A:ATacceptor_gain0.6600
13:94710637:GTTC:Gacceptor_gain0.6400
13:94710630:CTGC:Cacceptor_gain0.6300
13:94710656:G:Tacceptor_gain0.6200
13:94710636:AGTTC:Aacceptor_gain0.5700
13:94710627:GATC:Gacceptor_gain0.5200
13:94710523:G:Cacceptor_gain0.5100
13:94710512:T:Cacceptor_gain0.4800
13:94710612:GC:Gacceptor_gain0.4700
13:94710643:ATAGT:Aacceptor_gain0.4600
13:94711160:TCG:Tdonor_gain0.4400
13:94710638:TTC:Tacceptor_gain0.4300
13:94710512:T:TCacceptor_gain0.4200
13:94710635:AAGTT:Aacceptor_gain0.4100
13:94710612:G:Tacceptor_gain0.4000
13:94710632:GCAA:Gacceptor_gain0.4000
13:94710661:C:Tacceptor_gain0.4000
13:94710631:TGCA:Tacceptor_gain0.3700
13:94710522:C:CTacceptor_gain0.3600
13:94710614:T:Aacceptor_gain0.3600
13:94710634:A:ATacceptor_gain0.3600
13:94710665:GCTGC:Gacceptor_gain0.3600
13:94710613:CTT:Cacceptor_gain0.3400
13:94710635:AAGT:Aacceptor_gain0.3300
13:94710639:T:Aacceptor_gain0.3200
13:94710886:A:ACdonor_gain0.3100
13:94710887:C:CCdonor_gain0.3100
13:94710619:A:ACacceptor_gain0.3000

AlphaMissense

1759 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
13:94711804:C:AK82N1.000
13:94711804:C:GK82N1.000
13:94711806:T:CK82E1.000
13:94711809:G:AR81C1.000
13:94711809:G:TR81S1.000
13:94711812:G:AR80W1.000
13:94711814:G:AP79L1.000
13:94711814:G:TP79Q1.000
13:94711815:G:AP79S1.000
13:94711815:G:TP79T1.000
13:94711818:G:CR78G1.000
13:94711820:T:CY77C1.000
13:94711820:T:GY77S1.000
13:94711821:A:CY77D1.000
13:94711821:A:GY77H1.000
13:94711821:A:TY77N1.000
13:94711822:C:AK76N1.000
13:94711822:C:GK76N1.000
13:94711823:T:AK76M1.000
13:94711824:T:CK76E1.000
13:94711826:T:CY75C1.000
13:94711826:T:GY75S1.000
13:94711827:A:CY75D1.000
13:94711827:A:GY75H1.000
13:94711827:A:TY75N1.000
13:94711832:G:TP73H1.000
13:94711835:T:GH72P1.000
13:94711836:G:CH72D1.000
13:94711846:G:CH68Q1.000
13:94711846:G:TH68Q1.000

dbSNP variants (sampled 300 via entrez): RS1001172925 (13:94709719 G>A), RS1001332378 (13:94712227 C>T), RS1001614977 (13:94712491 C>T), RS1002336160 (13:94709955 A>G), RS1002997508 (13:94713509 G>C), RS1004405052 (13:94713291 T>A,C), RS1004821397 (13:94712203 G>A,C,T), RS1004950000 (13:94710782 T>G), RS1005002210 (13:94712049 T>G), RS1005126069 (13:94714161 C>T), RS1005661938 (13:94714476 C>A), RS1005693158 (13:94711069 G>T), RS1005979137 (13:94709745 C>T), RS1006445791 (13:94709468 T>C), RS1007076005 (13:94712114 T>A,C)

Disease associations

OMIM: gene MIM:604974 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

StudyTraitp-value
GCST012501_5Achilles tendon injury3.000000e-08

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0600078Achilles tendon injury

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation2
Cisplatinaffects expression, affects cotreatment, increases expression2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
bisphenol Adecreases expression1
sodium arsenateincreases abundance, decreases expression1
terbufosincreases methylation1
cobaltous chloridedecreases expression1
tetrabromobisphenol Adecreases expression1
ferrous chloridedecreases expression1
1-nitropyrenedecreases expression1
mono-benzyl phthalatedecreases methylation1
2-palmitoylglycerolincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
ICG 001decreases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, decreases expression1
jinfukangincreases expression, affects cotreatment1
(+)-JQ1 compounddecreases expression1
Temozolomideincreases expression1
Decitabineaffects expression1
Air Pollutantsdecreases expression1
Arsenicdecreases expression, increases abundance1
Arsenicalsdecreases expression1
Cytarabineincreases expression1
Diethylhexyl Phthalatedecreases expression1
Fonofosincreases methylation1
Parathionincreases methylation1
Phthalic Acidsincreases methylation1
Silicon Dioxidedecreases expression1
Testosteronedecreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot