PBX2

protein-coding

PBX homeobox 2, the group of TALE class homeoboxes and pseudogenes

Gene summary

This gene encodes a ubiquitously expressed member of the TALE/PBX homeobox family. It was identified by its similarity to a homeobox gene which is involved in t(1;19) translocation in acute pre-B-cell leukemias. This protein is a transcriptional activator which binds to the TLX1 promoter. The gene is located within the major histocompatibility complex (MHC) on chromosome 6. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002586.5

Inheritance

—

ClinVar variants

U:46B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr6:32,184,733-32,190,202

External References & Databases

Ensembl (ENSG00000204304)

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

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PBX2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 42

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002586.5. 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			1 clinvar			1
missense			42 clinvar	1 clinvar		43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	46	1	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002586.5	RefSeq	NP_002577.2	9	MANE Select
ENST00000375050.6	Ensembl	ENSP00000364190.3	9	MANE Select
ENST00001048779.1	Ensembl	ENSP00000718596.1	3	Standard
ENST00001089368.1	Ensembl	ENSP00000759174.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proximal/distal pattern formation
embryonic limb morphogenesis
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
chromatin binding
protein binding

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375050
Coding exons: 9
Length: 5452
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125747
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.84	170	252	0.674	0.0000142	2761
Missense (PolyPhen)		34	70.397	0.48298		872
Synonymous	2.51	67	98.8	0.678	0.00000569	862
Loss of Function	3.97	1	20.3	0.0493	0.00000107	226

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000020	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator that binds the sequence 5'- ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1. {ECO:0000269|PubMed:12609849}.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.159
RVIS EVS: -0.16
RVIS percentile EVS: 41.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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