SOX3
SRY-box transcription factor 3, the group of SRY-box transcription factors
Basic information
Region (hg38): X:140502985-140505069
Previous symbols: [ "PHP" ]
Links
Phenotypes
GenCC
Source:
- septooptic dysplasia (Supportive), mode of inheritance: AD
- 46,XX sex reversal 1 (Supportive), mode of inheritance: AD
- X-linked intellectual disability with isolated growth hormone deficiency (Supportive), mode of inheritance: XL
- X-linked congenital generalized hypertrichosis (Supportive), mode of inheritance: XL
- panhypopituitarism (Supportive), mode of inheritance: AR
- panhypopituitarism, X-linked (Limited), mode of inheritance: XL
- intellectual disability, X-linked, with panhypopituitarism (Limited), mode of inheritance: XL
- 46,XX sex reversal 3 (Definitive), mode of inheritance: XL
- intellectual disability, X-linked, with panhypopituitarism (Definitive), mode of inheritance: XL
- panhypopituitarism, X-linked (Strong), mode of inheritance: XL
- SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder (Moderate), mode of inheritance: XL
- panhypopituitarism, X-linked (Limited), mode of inheritance: XL
- 46,XX ovotesticular disorder of sex development (Limited), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Intellectual developmental disorder, X-linked, with panyhypopituitarism; Panhypopituitarism, X-linked | XL | Endocrine | Treatment for endocrine deficiencies, including those resulting in neonatal electrolyte abnormalities, may be beneficial | Endocrine; Musculoskeletal; Neurologic | 8826446; 9106538; 11031100; 12428212; 15800844; 16167084; 17400794; 21183788 |
| Deletions/insertions involving SOX3 regulatory regions can result in 46,XX sex reversal 3 (XL) or Hypoparathyroidism, X-linked by a position effect (XL) |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (67 variants)
- not_specified (55 variants)
- SOX3-related_disorder (17 variants)
- Intellectual_disability,_X-linked,_with_panhypopituitarism (14 variants)
- Panhypopituitarism,_X-linked (9 variants)
- History_of_neurodevelopmental_disorder (2 variants)
- Intellectual_disability (2 variants)
- Abnormal_sperm_morphology (1 variants)
- Premature_ovarian_insufficiency (1 variants)
- Abnormal_brain_morphology (1 variants)
- See_cases (1 variants)
- Oligospermia (1 variants)
- X-linked_intellectual_disability_with_isolated_growth_hormone_deficiency (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005634.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 18 | 24 | ||||
| missense | 59 | 12 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 62 | 30 | 6 |
Highest pathogenic variant AF is 0.0000010551049
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SOX3 | protein_coding | protein_coding | ENST00000370536 | 1 | 2074 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.449 | 0.525 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 76 | 153 | 0.497 | 0.0000101 | 2786 |
| Missense in Polyphen | 23 | 79.217 | 0.29034 | 1316 | ||
| Synonymous | 1.11 | 57 | 68.7 | 0.830 | 0.00000494 | 997 |
| Loss of Function | 1.79 | 1 | 5.54 | 0.180 | 3.50e-7 | 101 |
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: Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. Required also within the pharyngeal epithelia for craniofacial morphogenesis. Controls a genetic switch in male development. Is necessary for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity). {ECO:0000250, ECO:0000269|PubMed:21183788}.;
- Disease
- DISEASE: Panhypopituitarism X-linked (PHPX) [MIM:312000]: Affected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary. {ECO:0000269|PubMed:15800844}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, X-linked, with isolated growth hormone deficiency (MRXGH) [MIM:300123]: A disorder characterized by the association of variable degrees of mental retardation with panhypopituitarism, variable combinations of hypothyroidism, delayed pubertal development, and short stature due to growth hormone deficiency. {ECO:0000269|PubMed:12428212}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 46,XX sex reversal 3 (SRXX3) [MIM:300833]: A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:21183788}. Note=The disease is caused by mutations affecting the gene represented in this entry. Copy number variations (CNV) encompassing or in close proximity to SOX3 are responsible for XX male reversal. These variations include two duplications of approximately 123 kb and 85 kb, the former of which spans the entire SOX3 gene; a 343 kb deletion immediately upstream of SOX3 that is probably responsible of altered regulation (and not increased dosage) of SOX3; a large (approximately 6 Mb) duplication that encompasses SOX3 and at least 18 additional distally located genes. Its proximal breakpoint falls within the SOX3 regulatory region. This large rearrangement has been found in a patient with XX male reversal and a complex phenotype that also includes a scrotal hypoplasia, microcephaly, developmental delay, and growth retardation.;
- Pathway
- Signaling by WNT;Signal Transduction;Deactivation of the beta-catenin transactivating complex;TCF dependent signaling in response to WNT
(Consensus)
Recessive Scores
- pRec
- 0.399
Haploinsufficiency Scores
- pHI
- 0.983
- hipred
- hipred_score
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sox3
- Phenotype
- skeleton 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); reproductive system 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); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- sox3
- Affected structure
- epibranchial ganglion
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;central nervous system development;sensory organ development;sex determination;hypothalamus development;pituitary gland development;cell differentiation;neuron differentiation;negative regulation of neuron differentiation;face development;negative regulation of nucleic acid-templated transcription
- Cellular component
- nucleus;nucleoplasm;nuclear transcription factor complex
- Molecular function
- RNA polymerase II core promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;transcription corepressor activity