ITGB1BP1

protein-coding

integrin subunit beta 1 binding protein 1

Gene summary

The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domain. The interaction between this protein and beta1 integrin is highly specific. Two isoforms of this protein are derived from alternatively spliced transcripts. The shorter form of this protein does not interact with the beta1 integrin cytoplasmic domain. The longer form is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction, suggesting an important role of this protein during integrin-dependent cell adhesion. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

MANE transcript

NM_004763.5

Inheritance

—

ClinVar variants

U:27B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr2:9,403,475-9,423,528

External References & Databases

Ensembl (ENSG00000119185)

Transcript & Mutation Effects

hg38 • Region Span ~20.1 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 ITGB1BP1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004763.5. 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			2 clinvar			2
missense			23 clinvar	2 clinvar		25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	27	2	0	29

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 163 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004763.5	RefSeq	NP_004754.1	6	MANE Select
ENST00000355346.9	Ensembl	ENSP00000347504.4	6	MANE Select
NM_001319066.2	RefSeq	NP_001305995.1	6	Standard
NM_001319067.2	RefSeq	NP_001305996.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

blood vessel endothelial cell proliferation involved in sprouting angiogenesis
negative regulation of protein kinase activity
negative regulation of cell adhesion involved in substrate-bound cell migration
cell-matrix adhesion
Notch signaling pathway

Molecular Function

GDP-dissociation inhibitor activity
integrin binding
protein binding
protein transporter activity
protein kinase binding

Cellular Component

ruffle
nucleus
nucleoplasm
cytoplasm
microtubule organizing center

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360635
Coding exons: 6
Length: 20073
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.712	91	112	0.811	0.00000598	1300
Missense (PolyPhen)		39	42.303	0.92192		525
Synonymous	-0.141	45	43.8	1.03	0.00000269	373
Loss of Function	1.22	8	12.7	0.631	7.98e-7	136

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Key regulator of the integrin-mediated cell-matrix interaction signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. Plays a role in cell proliferation, differentiation, spreading, adhesion and migration in the context of mineralization and bone development and angiogenesis. Stimulates cellular proliferation in a fibronectin- dependent manner. Involved in the regulation of beta-1 integrin- containing focal adhesion (FA) site dynamics by controlling its assembly rate during cell adhesion; inhibits beta-1 integrin clustering within FA by directly competing with talin TLN1, and hence stimulates osteoblast spreading and migration in a fibronectin-and/or collagen-dependent manner. Acts as a guanine nucleotide dissociation inhibitor (GDI) by regulating Rho family GTPases during integrin-mediated cell matrix adhesion; reduces the level of active GTP-bound form of both CDC42 and RAC1 GTPases upon cell adhesion to fibronectin. Stimulates the release of active CDC42 from the membranes to maintain it in an inactive cytoplasmic pool. Participates in the translocation of the Rho-associated protein kinase ROCK1 to membrane ruffles at cell leading edges of the cell membrane, leading to an increase of myoblast cell migration on laminin. Plays a role in bone mineralization at a late stage of osteoblast differentiation; modulates the dynamic formation of focal adhesions into fibrillar adhesions, which are adhesive structures responsible for fibronectin deposition and fibrillogenesis. Plays a role in blood vessel development; acts as a negative regulator of angiogenesis by attenuating endothelial cell proliferation and migration, lumen formation and sprouting angiogenesis by promoting AKT phosphorylation and inhibiting ERK1/2 phosphorylation through activation of the Notch signaling pathway. Promotes transcriptional activity of the MYC promoter. {ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:11807099, ECO:0000269|PubMed:11919189, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:15703214, ECO:0000269|PubMed:17916086, ECO:0000269|PubMed:20616313, ECO:0000269|PubMed:21768292, ECO:0000269|Ref.19}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.361
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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