SOX5

SRY-box transcription factor 5, the group of SRY-box transcription factors

Basic information

Region (hg38): 12:23529503-24562544

Links

ENSG00000134532 ∙ NCBI:6660 ∙ OMIM:604975 ∙ HGNC:11201 ∙ Uniprot:P35711 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lamb-Shaffer syndrome (Strong), mode of inheritance: AD
• developmental and speech delay due to SOX5 deficiency (Supportive), mode of inheritance: AD
• Lamb-Shaffer syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lamb-Shaffer syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	22290657; 23220431; 23498568; 26111154

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX5 gene.

• not provided (79 variants)
• Lamb-Shaffer syndrome (71 variants)
• Inborn genetic diseases (23 variants)
• SOX5-related condition (4 variants)
• Intellectual disability (3 variants)
• not specified (2 variants)
• Severe global developmental delay;Generalized hypotonia;Epileptic encephalopathy (1 variants)
• Global developmental delay (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• Autism spectrum disorder (1 variants)
• Aplasia/Hypoplasia of the nails;Generalized hypotonia;Central hypotonia;Thoracolumbar scoliosis;Strabismus (1 variants)
• Cerebral visual impairment and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX5 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			2	16	6	24
missense	5	13	60	6		84
nonsense	13	4				17
start loss			1			1
frameshift	9	4				13
inframe indel						0
splice donor/acceptor (+/-2bp)	6	2				8
splice region			4	1	1	6
non coding			4	1	2	7
Total	33	23	67	23	8

Variants in SOX5

This is a list of pathogenic ClinVar variants found in the SOX5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-23534219-T-C			Uncertain significance (Feb 05, 2018)
12-23534228-T-G		Lamb-Shaffer syndrome	Uncertain significance (Aug 09, 2023)
12-23534259-C-A			Uncertain significance (Jun 01, 2022)
12-23534290-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
12-23534294-G-A			Likely benign (Nov 06, 2018)
12-23534362-C-T		Lamb-Shaffer syndrome	Uncertain significance (Aug 04, 2022)
12-23534377-T-C		Inborn genetic diseases	Likely benign (Feb 17, 2024)
12-23534384-G-C		Inborn genetic diseases	Likely benign (Dec 15, 2023)
12-23534419-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 11, 2023)
12-23534432-C-T			Benign (Dec 31, 2019)
12-23534433-G-A		Intellectual disability	Uncertain significance (Aug 05, 2019)
12-23534483-C-T			Likely benign (Mar 01, 2023)
12-23536464-G-T			Likely pathogenic (Oct 06, 2023)
12-23536466-A-T			Uncertain significance (Jun 08, 2021)
12-23536484-G-A			Uncertain significance (Apr 08, 2023)
12-23536512-A-C			Likely benign (Jul 20, 2018)
12-23536528-T-C			Uncertain significance (Apr 06, 2022)
12-23536546-G-T		Lamb-Shaffer syndrome • Intellectual disability	Likely pathogenic (Jan 06, 2017)
12-23536573-T-C		Lamb-Shaffer syndrome	Pathogenic (Jan 14, 2022)
12-23536574-A-G		Lamb-Shaffer syndrome	Likely pathogenic (Nov 23, 2021)
12-23536577-C-T		Lamb-Shaffer syndrome	Uncertain significance (Feb 09, 2023)
12-23536578-AG-A		Lamb-Shaffer syndrome	Pathogenic (Feb 02, 2024)
12-23536585-T-C		Lamb-Shaffer syndrome	Uncertain significance (May 16, 2022)
12-23536593-G-C		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
12-23536610-G-C		Cerebral visual impairment and intellectual disability	Likely pathogenic (Sep 09, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX5	protein_coding	protein_coding	ENST00000451604	15	421527

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000510	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.15	244	427	0.571	0.0000232	5018
Missense in Polyphen		77	214.81	0.35845		2495
Synonymous	-0.210	159	156	1.02	0.00000852	1478
Loss of Function	5.52	3	41.2	0.0728	0.00000215	458

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds specifically to the DNA sequence 5'-AACAAT-3'. Activates transcription of COL2A1 and AGC1 in vitro.
• Disease: DISEASE: Lamb-Shaffer syndrome (LAMSHF) [MIM:616803]: An autosomal dominant, neurodevelopmental disorder characterized by global developmental delay, intellectual disability, language and motor impairment, and distinct facial features. Additional variable skeletal abnormalities may also be present. {ECO:0000269|PubMed:22290657, ECO:0000269|PubMed:23220431, ECO:0000269|PubMed:23498568, ECO:0000269|PubMed:26111154}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation;Endochondral Ossification (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.0509
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.09

Haploinsufficiency Scores

• pHI: 0.631
• hipred: Y
• hipred_score: 0.809
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sox5
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial 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); 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); normal phenotype; respiratory system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: transcription by RNA polymerase II;positive regulation of chondrocyte differentiation;cell fate commitment;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;asymmetric neuroblast division;positive regulation of cartilage development;cellular response to transforming growth factor beta stimulus;positive regulation of mesenchymal stem cell differentiation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding