TLX3

protein-coding

T cell leukemia homeobox 3, the group of NKL subclass homeoboxes and pseudogenes

Gene summary

The protein encoded by this gene is an orphan homeobox protein that encodes a DNA-binding nuclear transcription factor. A translocation [t(5;14)(q35;q32)] involving this gene is associated with T-cell acute lymphoblastic leukemia (T-ALL) in children and young adults. [provided by RefSeq, Nov 2015]

Previous symbols:

HOX11L2

MANE transcript

NM_021025.4

Inheritance

—

ClinVar variants

U:38

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr5:171,309,248-171,312,139

External References & Databases

Ensembl (ENSG00000164438)

Transcript & Mutation Effects

hg38 • Region Span ~2.9 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 TLX3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 36

Hereditary breast ovarian cancer syndromeTotal: 1

TLX3-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021025.4. 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						0
missense			38 clinvar			38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	38	0	0	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021025.4	RefSeq	NP_066305.2	3	MANE Select
ENST00000296921.6	Ensembl	ENSP00000296921.5	3	MANE Select
ENST00001138423.1	Ensembl	ENSP00000805175.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)
Cell Differentiation - Index expanded
Cell Differentiation - Index
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Biological Process

neuron migration
regulation of respiratory gaseous exchange by neurological system process
regulation of transcription by RNA polymerase II
central nervous system development
respiratory gaseous exchange

Molecular Function

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

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296921
Coding exons: 3
Length: 2851
Individuals with no LoFs: 122477
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 122478
p: 0.00000408

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	119	170	0.698	0.00000777	1842
Missense (PolyPhen)		20	34.404	0.58132		369
Synonymous	-0.941	85	74.7	1.14	0.00000353	609
Loss of Function	1.90	2	7.66	0.261	3.29e-7	82

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000064	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	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.163

Intolerance Scores

LoFtool: 0.0391
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

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