ITGA2

protein-coding

integrin subunit alpha 2, the group of Integrin alpha subunits|CD molecules

Gene summary

This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Previous symbols:

CD49B

MANE transcript

NM_002203.4

Inheritance

ClinVar variants

U:157B:72

Top phenotype

platelet-type bleeding disorder 9

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr5:52,989,340-53,094,779

External References & Databases

Ensembl (ENSG00000164171)

Transcript & Mutation Effects

hg38 • Region Span ~105.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

platelet-type bleeding disorder 9STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013622

Submitter: Labcorp Genetics (formerly Invitae)

platelet-type bleeding disorder 9LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013622

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITGA2 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 130

not specifiedTotal: 61

Platelet-type bleeding disorder 9Total: 60

not providedTotal: 40

ITGA2-related disorderTotal: 40

Neonatal alloimmune thrombocytopeniaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002203.4. 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			7 clinvar	34 clinvar	2 clinvar	43
missense			140 clinvar	27 clinvar	9 clinvar	176
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	157	61	11	229

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002203.4	RefSeq	NP_002194.2	30	MANE Select
ENST00000296585.10	Ensembl	ENSP00000296585.5	30	MANE Select
ENST00000503810.6	Ensembl	ENSP00000426489.1	6	Standard
ENST00000509814.5	Ensembl	ENSP00000424397.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
ECM-receptor interaction - Homo sapiens (human)
Focal adhesion - Homo sapiens (human)
Dilated cardiomyopathy (DCM) - Homo sapiens (human)

Biological Process

response to hypoxia
positive regulation of leukocyte migration
substrate-dependent cell migration
hypotonic response
cell adhesion

Molecular Function

amyloid-beta binding
virus receptor activity
integrin binding
protein binding
collagen binding

Cellular Component

nucleus
plasma membrane
focal adhesion
integrin complex
external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296585
Coding exons: 30
Length: 105454
Individuals with no LoFs: 125580
Homozygous LoFs: 0
Heterozygous LoFs: 168
Defined: 125748
p: 0.000668

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.854	549	608	0.903	0.0000301	7766
Missense (PolyPhen)		176	220.78	0.79719		2886
Synonymous	-0.768	234	220	1.07	0.0000115	2234
Loss of Function	4.27	29	66.6	0.435	0.00000358	779

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00066	0.00065	rare
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.00076	0.00076	rare
South Asian	0.00095	0.00095	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.;

Recessive Scores

pRec: 0.624

Intolerance Scores

LoFtool: 0.501
RVIS EVS: -0.24
RVIS percentile EVS: 36.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

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