GeneBe

SOX5

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

Basic information

Region (hg38): 12:23529504-24562544

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
  • Lamb-Shaffer syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Lamb-Shaffer syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic22290657; 23220431; 23498568; 26111154

ClinVar

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

  • not_provided (119 variants)
  • Lamb-Shaffer_syndrome (94 variants)
  • Inborn_genetic_diseases (69 variants)
  • SOX5-related_disorder (16 variants)
  • not_specified (7 variants)
  • Intellectual_disability (5 variants)
  • Generalized_hypotonia (2 variants)
  • Epileptic_encephalopathy (1 variants)
  • Strabismus (1 variants)
  • Cerebral_visual_impairment_and_intellectual_disability (1 variants)
  • Tourette_syndrome (1 variants)
  • Autism_spectrum_disorder (1 variants)
  • Neurodevelopmental_delay (1 variants)
  • Thoracolumbar_scoliosis (1 variants)
  • Aplasia/Hypoplasia_of_the_nails (1 variants)
  • See_cases (1 variants)
  • Severe_global_developmental_delay (1 variants)
  • Central_hypotonia (1 variants)
  • Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
  • Developmental_disorder (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. These statistics are base on transcript: NM_000006940.6. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
20
clinvar
4
clinvar
 27
missense
5
clinvar
19
clinvar
130
clinvar
17
clinvar
 171
nonsense
17
clinvar
6
clinvar
 23
start loss
1
 1
frameshift
14
clinvar
5
clinvar
2
clinvar
 21
splice donor/acceptor (+/-2bp)
10
clinvar
4
clinvar
1
clinvar
 15
Total 46 34 136 38 4

Highest pathogenic variant AF is 0.00000657358

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SOX5protein_codingprotein_codingENST00000451604 15421527
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.0000510125741041257450.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.152444270.5710.00002325018
Missense in Polyphen77214.810.358452495
Synonymous-0.2101591561.020.000008521478
Loss of Function5.52341.20.07280.00000215458

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00006150.0000615
Ashkenazi Jewish0.00009920.0000992
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.000008830.00000879
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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