SOX4

SRY-box transcription factor 4, the group of SRY-box transcription factors

Basic information

Region (hg38): 6:21593751-21598619

Links

ENSG00000124766 ∙ NCBI:6659 ∙ OMIM:184430 ∙ HGNC:11200 ∙ Uniprot:Q06945 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coffin-Siris syndrome 10 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• Coffin-Siris syndrome 10 (Moderate), mode of inheritance: AD
• Coffin-Siris syndrome 10 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with speech delay and dysmorphic facies (Coffin-Siris syndrome 10)	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	30661772

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX4 gene.

• not provided (1 variants)
• Coffin-Siris syndrome 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX4 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				25	3	28
missense	1	2	85	7	1	96
nonsense	1	2	1			4
start loss						0
frameshift		1	7	2		10
inframe indel			5	2	3	10
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	2	5	98	36	9

Variants in SOX4

This is a list of pathogenic ClinVar variants found in the SOX4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-21593970-C-A			Benign (May 16, 2021)
6-21594549-C-G			Likely benign (Jul 01, 2022)
6-21594561-G-C			Uncertain significance (Dec 09, 2023)
6-21594562-A-G			Uncertain significance (Feb 10, 2023)
6-21594566-C-T			Uncertain significance (Jan 03, 2023)
6-21594586-G-T		Coffin-Siris syndrome 10	Uncertain significance (Jun 06, 2024)
6-21594590-G-C		Inborn genetic diseases	Uncertain significance (Aug 28, 2023)
6-21594597-C-A		SOX4-related disorder	Likely benign (Apr 24, 2020)
6-21594616-C-G		SOX4-related disorder	Benign (Jun 01, 2024)
6-21594625-GC-AA		Coffin-Siris syndrome 10	Uncertain significance (Jul 20, 2023)
6-21594664-G-T		Neurodevelopmental disorder	Uncertain significance (May 10, 2021)
6-21594664-GGCA-CGCT		Coffin-Siris syndrome 10	Pathogenic (Feb 02, 2023)
6-21594683-G-C		Coffin-Siris syndrome 10	Uncertain significance (Jun 04, 2020)
6-21594707-A-C		Coffin-Siris syndrome 10	Uncertain significance (Mar 22, 2022)
6-21594710-T-G		Coffin-Siris syndrome 10 • Intellectual disability;Mild facial and digital morphological abnormalities;Developmental delay	Pathogenic/Likely pathogenic (Feb 02, 2023)
6-21594716-G-A			Conflicting classifications of pathogenicity (Feb 07, 2022)
6-21594721-A-G		not specified	Uncertain significance (Jul 05, 2024)
6-21594727-G-A		Coffin-Siris syndrome 10	Uncertain significance (Sep 23, 2020)
6-21594732-C-A		Intellectual disability, mild • Coffin-Siris syndrome 10 • Developmental delay;Mild facial and digital morphological abnormalities;Intellectual disability	Likely pathogenic (Feb 20, 2019)
6-21594747-G-A			Likely benign (Apr 10, 2018)
6-21594763-A-G			Uncertain significance (Sep 26, 2021)
6-21594778-C-T			Uncertain significance (May 12, 2023)
6-21594812-T-A			Uncertain significance (Nov 01, 2019)
6-21594815-G-A		Coffin-Siris syndrome 10	Likely pathogenic (Sep 20, 2023)
6-21594823-T-G			Pathogenic (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX4	protein_coding	protein_coding	ENST00000244745	1	4876

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.927	0.0731	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	150	196	0.765	0.00000902	2971
Missense in Polyphen		9	50.031	0.17989		563
Synonymous	-5.14	157	93.7	1.67	0.00000469	1027
Loss of Function	2.68	0	8.34	0.00	3.61e-7	117

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: dbNSFP

• Function: FUNCTION: Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif.
• Pathway: MicroRNAs in cancer - Homo sapiens (human);H19 action Rb-E2F1 signaling and CDK-β-catenin activity;Signaling by WNT;Signal Transduction;Deactivation of the beta-catenin transactivating complex;IL5;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.260

Haploinsufficiency Scores

• pHI: 0.961
• hipred: Y
• hipred_score: 0.807
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sox4
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail 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); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; 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); 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); endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; 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)

Zebrafish Information Network

• Gene name: sox4b
• Affected structure: glucagon secreting cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: skeletal system development;neural tube formation;pro-B cell differentiation;mitral valve morphogenesis;cardiac ventricle formation;cardiac right ventricle morphogenesis;atrial septum primum morphogenesis;noradrenergic neuron differentiation;regulation of transcription, DNA-templated;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;heart development;positive regulation of cell population proliferation;negative regulation of cell population proliferation;glial cell proliferation;spinal cord development;spinal cord motor neuron differentiation;glial cell development;cell differentiation;T cell differentiation;endocrine pancreas development;negative regulation of protein ubiquitination;regulation of protein stability;positive regulation of insulin secretion;somatic stem cell population maintenance;ascending aorta morphogenesis;glucose homeostasis;DNA damage response, detection of DNA damage;positive regulation of apoptotic process;positive regulation of translation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;sympathetic nervous system development;protein stabilization;limb bud formation;ventricular septum morphogenesis;negative regulation of cell death;neuroepithelial cell differentiation;kidney morphogenesis;cellular response to glucose stimulus;positive regulation of canonical Wnt signaling pathway;positive regulation of N-terminal peptidyl-lysine acetylation
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;nuclear transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;protein heterodimerization activity