PBX3

protein-coding

PBX homeobox 3, the group of TALE class homeoboxes and pseudogenes

Gene summary

Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including eye development; nervous system development; and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult locomotory behavior; dorsal spinal cord development; and regulation of respiratory gaseous exchange by nervous system process. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006195.6

Inheritance

—

ClinVar variants

P:3U:43

Top phenotype

X-linked cone-rod dystrophy

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr9:125,747,345-125,967,377

External References & Databases

Ensembl (ENSG00000167081)

Transcript & Mutation Effects

hg38 • Region Span ~220.0 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 PBX3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 40

X-linked cone-rod dystrophyTotal: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006195.6. 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			42 clinvar			42
nonsense			1 clinvar			1
start loss						0
frameshift		3 clinvar				3
splice donor/acceptor (+/-2bp)						0
Total	0	3	43	0	0	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006195.6	RefSeq	NP_006186.1	9	MANE Select
ENST00000373489.10	Ensembl	ENSP00000362588.5	9	MANE Select
NM_001134778.2	RefSeq	NP_001128250.1	8	Standard
NM_001330782.2	RefSeq	NP_001317711.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)
Mesodermal Commitment Pathway
miR-509-3p alteration of YAP1-ECM axis

Biological Process

regulation of respiratory gaseous exchange by neurological system process
anterior compartment pattern formation
posterior compartment specification
respiratory gaseous exchange
adult locomotory behavior

Molecular Function

RNA polymerase II distal enhancer sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373489
Coding exons: 9
Length: 220033
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.16	147	242	0.608	0.0000123	2846
Missense (PolyPhen)		22	85.444	0.25748		1036
Synonymous	0.578	85	92.1	0.923	0.00000516	818
Loss of Function	3.37	5	22.1	0.226	0.00000119	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.000097	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator that binds the sequence 5'- ATCAATCAA-3'.;

Recessive Scores

pRec: 0.0726

Intolerance Scores

LoFtool: 0.193
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: 1.00

Gene Damage Prediction

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