PBX1

Chr 1AD

PBX homeobox 1

Also known as: CAKUHED

NCBI Gene: 5087 ENSG00000185630 UniProt: P40424 OMIM: 176310

This gene encodes PBX1, a transcription factor that binds specific DNA sequences as part of heterodimers with HOX proteins to regulate gene expression during development. Mutations cause congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variation (pLI 0.995, LOEUF 0.255), indicating that functional copies are critical for normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nuclear protein that belongs to the PBX homeobox family of transcriptional factors. Studies in mice suggest that this gene may be involved in the regulation of osteogenesis and required for skeletal patterning and programming. A chromosomal translocation, t(1;19) involving this gene and TCF3/E2A gene, is associated with pre-B-cell acute lymphoblastic leukemia. The resulting fusion protein, in which the DNA binding domain of E2A is replaced by the DNA binding domain of this protein, transforms cells by constitutively activating transcription of genes regulated by the PBX protein family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delayMIM #617641

Clinical highlights

Gene-disease validity (ClinGen)

congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

101

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

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