SOX8

protein-coding

SRY-box transcription factor 8, the group of SRY-box transcription factors

Gene summary

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein may be involved in brain development and function. Haploinsufficiency for this protein may contribute to the cognitive disability found in an alpha-thalassemia-related syndrome (ART-16). This protein is also highly expressed in the majority of human hepatocellular carcinomas and promotes cellular proliferation and enhanced tumor growth. [provided by RefSeq, Jul 2017]

MANE transcript

NM_014587.5

Inheritance

ClinVar variants

P:1U:84B:27

Top phenotype

SOX8-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr16:981,444-986,979

External References & Databases

Ensembl (ENSG00000005513)

Transcript & Mutation Effects

hg38 • Region Span ~5.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOX8 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 84

not providedTotal: 17

SOX8-related disorderTotal: 17

46 XY differences of sex developmentTotal: 2

Aplasia of the ovaryTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014587.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				15 clinvar	4 clinvar	19
missense		1 clinvar	84 clinvar	8 clinvar		93
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	84	23	4	112

Highest pathogenic variant AF is 0.000028343207

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014587.5	RefSeq	NP_055402.2	3	MANE Select
ENST00000293894.4	Ensembl	ENSP00000293894.3	3	MANE Select
ENST00000711625.1	Ensembl	ENSP00000518813.1	2	Standard
ENST00000711626.1	Ensembl	ENSP00000518814.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Preimplantation Embryo

Biological Process

osteoblast differentiation
in utero embryonic development
neural crest cell migration
morphogenesis of an epithelium
signal transduction

Molecular Function

RNA polymerase II core 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 binding

Cellular Component

nucleus
cytoplasm
nuclear transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293894
Coding exons: 3
Length: 5172
Individuals with no LoFs: 122355
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 122360
p: 0.0000204

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.888	230	271	0.848	0.0000192	2789
Missense (PolyPhen)		77	117.56	0.65499		1308
Synonymous	-1.72	159	134	1.19	0.0000116	915
Loss of Function	2.72	2	12.3	0.163	6.07e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000050	0.000048	rare
European (Non-Finnish)	0.000029	0.000027	rare
South Asian	0.000035	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in central nervous system, limb and facial development. May be involved in male sex determination. Binds the consensus motif 5'-[AT][AT]CAA[AT]G-3' (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.795

Gene Damage Prediction

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