SOX9
SRY-box transcription factor 9, the group of SRY-box transcription factors
Basic information
Region (hg38): 17:72121019-72126416
Previous symbols: [ "CMD1", "CMPD1" ]
Links
Phenotypes
GenCC
Source:
- campomelic dysplasia (Definitive), mode of inheritance: AD
- campomelic dysplasia (Strong), mode of inheritance: AD
- isolated Pierre-Robin syndrome (Supportive), mode of inheritance: AD
- campomelic dysplasia (Supportive), mode of inheritance: AD
- 46,XY complete gonadal dysgenesis (Supportive), mode of inheritance: AD
- 46,XX ovotesticular disorder of sex development (Supportive), mode of inheritance: AD
- 46,XX sex reversal 1 (Supportive), mode of inheritance: AD
- 46,XY partial gonadal dysgenesis (Supportive), mode of inheritance: AD
- isolated Pierre-Robin syndrome (Limited), mode of inheritance: AD
- Cooks syndrome (Limited), mode of inheritance: AD
- campomelic dysplasia (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| 46, XY sex reversal 10; Campomelic dysplasia | AD | Cardiovascular; Oncologic | Individuals with a 46,XY karyotype and genital undermasculinization may have an increased risk of gonadoblastoma, and gonadal removal has been recommended; The conditions can involve congenital cardiac anomalies, and awareness may allow early management | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic; Renal; Genitourinary | 10588843; 20301724; 21208124; 25604083 |
ClinVar
This is a list of variants' phenotypes submitted to
- Camptomelic dysplasia (224 variants)
- not provided (107 variants)
- Inborn genetic diseases (23 variants)
- not specified (17 variants)
- Connective tissue disorder (13 variants)
- SOX9-related condition (8 variants)
- Campomelic dysplasia with autosomal sex reversal (5 variants)
- Acampomelic campomelic dysplasia (2 variants)
- Sex reversal (1 variants)
- Bent bone dysplasia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX9 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 54 | 69 | ||||
| missense | 10 | 24 | 89 | 14 | 141 | |
| nonsense | 18 | 24 | ||||
| start loss | 0 | |||||
| frameshift | 21 | 11 | 33 | |||
| inframe indel | 10 | 13 | ||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| splice region ? | 3 | 3 | 6 | |||
| non coding ? | 12 | 25 | ||||
| Total | 54 | 41 | 114 | 82 | 19 |
Variants in SOX9
This is a list of pathogenic ClinVar variants found in the SOX9 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-72121223-G-A | Benign/Likely benign (Oct 08, 2021) | |||
| 17-72121236-T-A | Likely benign (Jul 30, 2019) | |||
| 17-72121309-G-A | Benign (Mar 03, 2015) | |||
| 17-72121406-C-G | Camptomelic dysplasia | Uncertain significance (Jun 25, 2022) | ||
| 17-72121406-C-T | Camptomelic dysplasia | Conflicting classifications of pathogenicity (Mar 30, 2023) | ||
| 17-72121407-C-T | Camptomelic dysplasia • Inborn genetic diseases | Conflicting classifications of pathogenicity (Jan 01, 2024) | ||
| 17-72121409-C-T | not specified • Camptomelic dysplasia | Likely benign (Jul 12, 2022) | ||
| 17-72121433-G-A | Camptomelic dysplasia | Benign (Jan 18, 2024) | ||
| 17-72121439-G-A | Camptomelic dysplasia • SOX9-related disorder | Likely benign (Feb 13, 2023) | ||
| 17-72121444-T-C | Camptomelic dysplasia | Uncertain significance (May 09, 2023) | ||
| 17-72121446-T-A | Camptomelic dysplasia | Likely benign (Jul 09, 2021) | ||
| 17-72121447-C-T | Camptomelic dysplasia | Uncertain significance (May 16, 2022) | ||
| 17-72121450-G-C | Camptomelic dysplasia | Uncertain significance (May 19, 2022) | ||
| 17-72121452-G-A | Malignant tumor of prostate | Uncertain significance (-) | ||
| 17-72121452-GC-G | SOX9-related disorder | Likely pathogenic (Jan 05, 2024) | ||
| 17-72121458-AG-A | Connective tissue disorder | Likely pathogenic (Apr 01, 2020) | ||
| 17-72121467-A-G | Camptomelic dysplasia • SOX9-related disorder | Benign/Likely benign (Dec 11, 2023) | ||
| 17-72121468-T-A | Camptomelic dysplasia | Uncertain significance (Dec 13, 2021) | ||
| 17-72121471-C-A | Camptomelic dysplasia | Likely benign (Aug 24, 2023) | ||
| 17-72121499-G-T | Camptomelic dysplasia | Likely benign (Aug 19, 2022) | ||
| 17-72121502-G-T | Camptomelic dysplasia | Likely benign (Apr 14, 2021) | ||
| 17-72121513-C-CG | Camptomelic dysplasia | Pathogenic (Jan 25, 2021) | ||
| 17-72121529-G-A | Camptomelic dysplasia | Likely benign (Jul 07, 2023) | ||
| 17-72121531-G-A | Camptomelic dysplasia | Uncertain significance (Oct 24, 2023) | ||
| 17-72121532-G-A | Camptomelic dysplasia | Likely benign (Dec 18, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SOX9 | protein_coding | protein_coding | ENST00000245479 | 3 | 5401 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00228 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 230 | 311 | 0.740 | 0.0000171 | 3299 |
| Missense in Polyphen | 52 | 101.25 | 0.51356 | 1035 | ||
| Synonymous | -2.26 | 182 | 147 | 1.24 | 0.00000974 | 1012 |
| Loss of Function | 3.91 | 0 | 17.8 | 0.00 | 8.62e-7 | 181 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional regulator that plays a role in chondrocytes differentiation and skeletal development (PubMed:24038782). Binds to the COL2A1 promoter and activates COL2A1 expression, as part of a complex with ZNF219 (By similarity). {ECO:0000250|UniProtKB:Q04887, ECO:0000269|PubMed:24038782}.;
- Disease
- DISEASE: Campomelic dysplasia (CMD1) [MIM:114290]: A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females. {ECO:0000269|PubMed:10446171, ECO:0000269|PubMed:10951468, ECO:0000269|PubMed:11323423, ECO:0000269|PubMed:11754051, ECO:0000269|PubMed:12783851, ECO:0000269|PubMed:19033726, ECO:0000269|PubMed:19921652, ECO:0000269|PubMed:20513132, ECO:0000269|PubMed:24038782, ECO:0000269|PubMed:7485151, ECO:0000269|PubMed:9002675, ECO:0000269|PubMed:9452059}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 46,XX sex reversal 2 (SRXX2) [MIM:278850]: A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:21208124}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 46,XY sex reversal 10 (SRXY10) [MIM:616425]: A disorder of sex development. Affected individuals have a 46,XY karyotype, show gonadal dysgenesis with streak gonads, look like normal females at birth, do not develop secondary sexual characteristics at puberty and do not menstruate. {ECO:0000269|PubMed:25604083}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- cAMP signaling pathway - Homo sapiens (human);Neural Crest Differentiation;Spinal Cord Injury;Endochondral Ossification;Prostaglandin Synthesis and Regulation;Transcriptional regulation by RUNX2;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Deactivation of the beta-catenin transactivating complex;TGF_beta_Receptor;TCF dependent signaling in response to WNT
(Consensus)
Recessive Scores
- pRec
- 0.836
Intolerance Scores
- loftool
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.4
Haploinsufficiency Scores
- pHI
- 0.853
- hipred
- Y
- hipred_score
- 0.880
- ghis
- 0.587
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sox9
- Phenotype
- renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- sox9b
- Affected structure
- iridophore
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- skeletal system development;cartilage condensation;ossification;branching involved in ureteric bud morphogenesis;cell fate specification;epithelial to mesenchymal transition;tissue homeostasis;positive regulation of protein phosphorylation;hair follicle development;morphogenesis of an epithelium;positive regulation of mesenchymal cell proliferation;chondrocyte differentiation;negative regulation of immune system process;heart valve development;heart valve morphogenesis;aortic valve morphogenesis;heart valve formation;endocardial cushion morphogenesis;chondrocyte differentiation involved in endochondral bone morphogenesis;chondrocyte hypertrophy;nucleosome assembly;chromatin remodeling;transcription initiation from RNA polymerase II promoter;cytoskeleton organization;signal transduction;epidermal growth factor receptor signaling pathway;Notch signaling pathway;spermatogenesis;central nervous system development;heart development;positive regulation of cell population proliferation;male gonad development;regulation of cell cycle process;positive regulation of epithelial cell migration;neural crest cell development;neural crest cell fate specification;positive regulation of phosphatidylinositol 3-kinase signaling;male germ-line sex determination;cAMP-mediated signaling;regulation of cell adhesion;extracellular matrix organization;negative regulation of ossification;negative regulation of bone mineralization;prostate gland development;negative regulation of epithelial cell differentiation;positive regulation of epithelial cell differentiation;mammary gland development;notochord development;otic vesicle formation;endocrine pancreas development;negative regulation of chondrocyte differentiation;positive regulation of chondrocyte differentiation;lacrimal gland development;protein localization to nucleus;somatic stem cell population maintenance;intrahepatic bile duct development;regulation of cell population proliferation;regulation of apoptotic process;negative regulation of apoptotic process;protein kinase B signaling;negative regulation of myoblast differentiation;positive regulation of protein catabolic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of photoreceptor cell differentiation;oligodendrocyte differentiation;positive regulation of epithelial cell proliferation;negative regulation of epithelial cell proliferation;cartilage development;Sertoli cell differentiation;Sertoli cell development;astrocyte fate commitment;retina development in camera-type eye;limb bud formation;retinal rod cell differentiation;epithelial tube branching involved in lung morphogenesis;lung epithelial cell differentiation;epithelial cell proliferation involved in prostatic bud elongation;bronchus cartilage development;trachea cartilage development;intestinal epithelial structure maintenance;regulation of cell proliferation involved in tissue homeostasis;positive regulation of cartilage development;regulation of branching involved in lung morphogenesis;morphogenesis of a branching epithelium;lung smooth muscle development;protein-containing complex assembly;negative regulation of biomineral tissue development;ERK1 and ERK2 cascade;Harderian gland development;cellular response to mechanical stimulus;cellular response to retinoic acid;cellular response to interleukin-1;cellular response to epidermal growth factor stimulus;cellular response to heparin;cellular response to transforming growth factor beta stimulus;cellular response to BMP stimulus;renal vesicle induction;ureter urothelium development;ureter smooth muscle cell differentiation;ureter morphogenesis;metanephric nephron tubule formation;negative regulation of canonical Wnt signaling pathway;cochlea morphogenesis;positive regulation of kidney development;positive regulation of branching involved in ureteric bud morphogenesis;anterior head development;cell-cell adhesion;positive regulation of extracellular matrix assembly;negative regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of male gonad development;positive regulation of cell proliferation involved in heart morphogenesis;positive regulation of mesenchymal stem cell differentiation;regulation of epithelial cell proliferation involved in lung morphogenesis;negative regulation of mesenchymal cell apoptotic process
- Cellular component
- nucleus;nucleoplasm;protein-containing complex;nuclear transcription factor complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;beta-catenin binding;protein kinase A catalytic subunit binding;enhancer binding;bHLH transcription factor binding;protein heterodimerization activity;pre-mRNA intronic binding