PBX1

PBX homeobox 1, the group of TALE class homeoboxes and pseudogenes

Basic information

Region (hg38): 1:164555583-164899296

Links

ENSG00000185630 ∙ NCBI:5087 ∙ OMIM:176310 ∙ HGNC:8632 ∙ Uniprot:P40424 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (Strong), mode of inheritance: AD
• congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (Strong), mode of inheritance: AD
• congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (Strong), mode of inheritance: AD
• congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital anomalies of the kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (CAKUTHED)	AD	Audiologic/Otolaryngologic; Renal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with a variety of renal anomalies and monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	Audiologic/Otolaryngologic; Craniofacial; Neurologic; Renal	28270404; 28566479

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PBX1 gene.

• not provided (47 variants)
• Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (30 variants)
• Inborn genetic diseases (7 variants)
• PBX1-related condition (6 variants)
• PBX1-related intellectual disability and pleiotropic developmental defects (1 variants)
• Autism spectrum disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PBX1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	1	8
missense	3	9	17	2	1	32
nonsense	9	3				12
start loss						0
frameshift	7		1			8
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)		4				4
splice region				1		1
non coding		1		6	5	12
Total	19	18	20	15	7

Highest pathogenic variant AF is 0.00000658

Variants in PBX1

This is a list of pathogenic ClinVar variants found in the PBX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-164559839-G-GGCTGATGCATTCCCAT		PBX1-related disorder	Uncertain significance (Dec 28, 2022)
1-164559852-C-G			Likely benign (Jan 01, 2023)
1-164559854-A-G			Uncertain significance (Jul 09, 2022)
1-164559873-C-T			Likely benign (Jun 20, 2023)
1-164559874-G-T		See cases	Pathogenic (Apr 26, 2021)
1-164559883-G-A			Benign (Jan 30, 2024)
1-164559888-GT-G		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Pathogenic (Oct 30, 2020)
1-164559899-T-A		PBX1-related disorder	Likely pathogenic (Dec 19, 2022)
1-164559900-G-A		PBX1-related disorder	Benign/Likely benign (Nov 13, 2023)
1-164559914-G-T			Likely benign (Sep 21, 2022)
1-164559935-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
1-164559943-C-T		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Pathogenic (Aug 03, 2023)
1-164559958-AT-A			Pathogenic (Jun 10, 2018)
1-164559967-C-T		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Likely pathogenic (Jul 25, 2018)
1-164559973-A-ATGAC		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Likely pathogenic (Sep 08, 2022)
1-164560009-G-T			Likely benign (Aug 10, 2022)
1-164563218-ATGT-A			Likely benign (Aug 22, 2023)
1-164563238-A-G		Inborn genetic diseases	Likely benign (Dec 01, 2023)
1-164563309-CAGGT-C		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Likely pathogenic (Oct 01, 2019)
1-164563312-G-A		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Likely pathogenic (Jun 30, 2021)
1-164792478-C-CTT		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Benign (Jan 28, 2024)
1-164792499-A-C			Uncertain significance (Apr 13, 2023)
1-164792505-C-T		Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay	Pathogenic/Likely pathogenic (Jul 25, 2023)
1-164792531-A-G			Likely benign (May 05, 2023)
1-164792542-T-A		PBX1-related disorder	Uncertain significance (May 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PBX1	protein_coding	protein_coding	ENST00000420696	9	343713

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00473	125707	0	2	125709	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.83	81	252	0.322	0.0000149	2795
Missense in Polyphen		16	111.71	0.14322		1225
Synonymous	0.924	90	102	0.884	0.00000658	821
Loss of Function	4.23	2	24.7	0.0811	0.00000139	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000293	0.0000293
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds the sequence 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. Converted into a potent transcriptional activator by the (1;19) translocation. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4. Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B. Together with NKX2-5, it is required for spleen development through a mechanism that involves CDKN2B repression (By similarity). {ECO:0000250, ECO:0000269|PubMed:12609849, ECO:0000269|PubMed:21746878}.
• Disease: DISEASE: Note=A chromosomal aberration involving PBX1 is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. {ECO:0000269|PubMed:1671560, ECO:0000269|PubMed:1967983}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Mesodermal Commitment Pathway;Preimplantation Embryo;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Signal Transduction;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;Glucocorticoid receptor regulatory network;Transcriptional regulation of pluripotent stem cells (Consensus)

Recessive Scores

• pRec: 0.0957

Intolerance Scores

• loftool: 0.189
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.840
• hipred: Y
• hipred_score: 0.825
• ghis: 0.473

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pbx1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: pbx1a
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: branching involved in ureteric bud morphogenesis;steroid biosynthetic process;positive regulation of transcription of Notch receptor target;sex differentiation;positive regulation of cell population proliferation;anterior/posterior pattern specification;proximal/distal pattern formation;positive regulation of G2/M transition of mitotic cell cycle;regulation of ossification;adrenal gland development;embryonic limb morphogenesis;somatic stem cell population maintenance;embryonic hemopoiesis;negative regulation of neuron differentiation;spleen development;thymus development;embryonic skeletal system development
• Cellular component: nucleus;nucleoplasm;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;protein heterodimerization activity