TOX

protein-coding

thymocyte selection associated high mobility group box, the group of thymocyte selection associated high mobility group box family

Gene summary

The protein encoded by this gene contains a HMG box DNA binding domain. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. This protein may function to regulate T-cell development.[provided by RefSeq, Apr 2009]

MANE transcript

NM_014729.3

Inheritance

—

ClinVar variants

U:75B:2

Top phenotype

Iron-refractory iron deficiency anemia

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr8:58,805,412-59,119,147

External References & Databases

Ensembl (ENSG00000198846)

Transcript & Mutation Effects

hg38 • Region Span ~313.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOX variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 2

Iron-refractory iron deficiency anemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014729.3. 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			2 clinvar	1 clinvar		3
missense			72 clinvar	1 clinvar		73
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	75	2	0	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014729.3	RefSeq	NP_055544.1	9	MANE Select
ENST00000361421.2	Ensembl	ENSP00000354842.1	9	MANE Select
ENST00000890858.1	Ensembl	ENSP00000560917.1	8	Standard
ENST00000890858.2	Ensembl	ENSP00000560917.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Development and heterogeneity of the ILC family

Biological Process

regulation of transcription by RNA polymerase II
lymphocyte differentiation
positive regulation of natural killer cell differentiation
lymph node development
Peyer's patch development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361421
Coding exons: 9
Length: 313791
Individuals with no LoFs: 125319
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125321
p: 0.00000798

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	240	298	0.804	0.0000148	3473
Missense (PolyPhen)		103	146.72	0.70201		1767
Synonymous	1.13	102	118	0.868	0.00000692	1018
Loss of Function	4.32	1	23.7	0.0422	0.00000111	269

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in regulating T-cell development. {ECO:0000250}.;

Recessive Scores

pRec: 0.200

Intolerance Scores

LoFtool: 0.203
RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.855

Gene Damage Prediction

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