PBXIP1

protein-coding

PBX homeobox interacting protein 1

Gene summary

The protein encoded by this gene interacts with the PBX1 homeodomain protein, inhibiting its transcriptional activation potential by preventing its binding to DNA. The encoded protein, which is primarily cytosolic but can shuttle to the nucleus, also can interact with estrogen receptors alpha and beta and promote the proliferation of breast cancer, brain tumors, and lung cancer. Several transcript variants encoding different isoforms have been found for this gene. More variants exist, but their full-length natures have yet to be determined. [provided by RefSeq, Dec 2015]

MANE transcript

NM_020524.4

Inheritance

—

ClinVar variants

U:125B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr1:154,944,076-154,956,123

External References & Databases

Ensembl (ENSG00000163346)

Transcript & Mutation Effects

hg38 • Region Span ~12.0 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 PBXIP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020524.4. 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			1 clinvar	3 clinvar		4
missense			115 clinvar	5 clinvar		120
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	125	8	0	133

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020524.4	RefSeq	NP_065385.2	10	MANE Select
ENST00000368463.8	Ensembl	ENSP00000357448.3	10	MANE Select
NM_001317734.2	RefSeq	NP_001304663.1	9	Standard
NM_001317735.2	RefSeq	NP_001304664.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development
cell differentiation
negative regulation of transcription, DNA-templated

Molecular Function

transcription corepressor activity
protein binding

Cellular Component

nucleus
cytosol
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368463
Coding exons: 10
Length: 12048
Individuals with no LoFs: 125650
Homozygous LoFs: 0
Heterozygous LoFs: 98
Defined: 125748
p: 0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.793	363	408	0.890	0.0000232	4726
Missense (PolyPhen)		95	122.64	0.77463		1477
Synonymous	1.31	145	167	0.870	0.00000856	1486
Loss of Function	1.91	21	32.8	0.640	0.00000159	353

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00075	0.00074	rare
Latino/Admixed American	0.00026	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00098	0.00098	rare
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.00036	0.00035	rare
South Asian	0.00052	0.00052	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulator of pre-B-cell leukemia transcription factors (BPXs) function. Inhibits the binding of PBX1-HOX complex to DNA and blocks the transcriptional activity of E2A-PBX1. Tethers estrogen receptor-alpha (ESR1) to microtubules and allows them to influence estrogen receptors-alpha signaling. {ECO:0000269|PubMed:10825160, ECO:0000269|PubMed:12360403, ECO:0000269|PubMed:17043237}.;

Recessive Scores

pRec: 0.0906

Intolerance Scores

LoFtool: 0.936
RVIS EVS: -0.02
RVIS percentile EVS: 52.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.373

Gene Damage Prediction

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