Mutagenetix > Incidental Mutation

Incidental Mutation 'P0007:Itga2'

7589

Institutional Source

Beutler Lab

Gene Symbol

Itga2

Ensembl Gene

ENSMUSG00000015533

Gene Name

integrin alpha 2

Synonyms

DX5, VLA-2 receptor, alpha 2 subunit, CD49B

MMRRC Submission

038263-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

P0007 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

114969617-115068636 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 115002735 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 585 (I585N)

Ref Sequence

ENSEMBL: ENSMUSP00000053891 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056117]

AlphaFold

Q62469

Predicted Effect

probably damaging
Transcript: ENSMUST00000056117
AA Change: I585N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000053891
Gene: ENSMUSG00000015533
AA Change: I585N

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
Int_alpha	41	96	4.91e-4	SMART
VWA	169	359	2.42e-39	SMART
Blast:VWA	364	424	4e-26	BLAST
Int_alpha	430	481	2.59e-3	SMART
Int_alpha	484	541	3.5e-9	SMART
Int_alpha	547	602	3.11e-15	SMART
Int_alpha	611	669	2.52e-1	SMART
low complexity region	890	910	N/A	INTRINSIC
transmembrane domain	1129	1151	N/A	INTRINSIC
Pfam:Integrin_alpha	1152	1166	9e-7	PFAM

Meta Mutation Damage Score

0.7824

Coding Region Coverage

1x: 85.2%
3x: 80.2%
10x: 65.3%
20x: 42.8%

Validation Efficiency

94% (102/109)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Homozygotes for targeted null mutations were viable, fertile, showed no overt anatomical defects, and exhibited no bleeding anomalies. Platelet, primary fibroblast and keratinocytes from homozygous mutant mice show less efficient adhesion to collagens in vitro. [provided by MGI curators]

Allele List at MGI

All alleles(6) : Targeted(6)

Other mutations in this stock

Total: 8 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts6	A	G	13: 104,433,999 (GRCm39)	T143A	possibly damaging	Het
Cfap74	T	A	4: 155,506,685 (GRCm39)	S139T	possibly damaging	Het
Fbxo7	T	C	10: 85,869,157 (GRCm39)	S204P	possibly damaging	Het
Lgi3	A	G	14: 70,774,152 (GRCm39)	Y442C	probably damaging	Het
Magi1	A	G	6: 93,722,969 (GRCm39)	I530T	probably damaging	Het
Med12l	T	C	3: 58,998,816 (GRCm39)		probably benign	Het
Nbeal1	A	G	1: 60,358,847 (GRCm39)	I1176M	probably damaging	Het
Ostn	G	T	16: 27,143,279 (GRCm39)	G36*	probably null	Het

Other mutations in Itga2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00809:Itga2	APN	13	115,014,161 (GRCm39)	missense	probably damaging	0.99
IGL01481:Itga2	APN	13	114,996,168 (GRCm39)	missense	possibly damaging	0.63
IGL01666:Itga2	APN	13	114,973,627 (GRCm39)	critical splice donor site	probably null
IGL01730:Itga2	APN	13	114,990,947 (GRCm39)	splice site	probably benign
IGL01965:Itga2	APN	13	114,984,600 (GRCm39)	splice site	probably benign
IGL01987:Itga2	APN	13	114,984,482 (GRCm39)	nonsense	probably null
IGL02334:Itga2	APN	13	115,001,845 (GRCm39)	critical splice donor site	probably null
IGL02381:Itga2	APN	13	114,993,258 (GRCm39)	missense	probably damaging	1.00
IGL02562:Itga2	APN	13	114,973,106 (GRCm39)	unclassified	probably benign
IGL03191:Itga2	APN	13	114,973,020 (GRCm39)	unclassified	probably benign
IGL03209:Itga2	APN	13	115,017,168 (GRCm39)	missense	probably damaging	1.00
R0023:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0023:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0025:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0029:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0062:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0062:Itga2	UTSW	13	115,007,032 (GRCm39)	missense	possibly damaging	0.90
R0149:Itga2	UTSW	13	114,973,115 (GRCm39)	unclassified	probably benign
R0152:Itga2	UTSW	13	115,002,850 (GRCm39)	missense	probably benign	0.06
R0496:Itga2	UTSW	13	114,990,435 (GRCm39)	missense	probably benign	0.00
R0502:Itga2	UTSW	13	114,982,392 (GRCm39)	missense	probably benign	0.15
R0599:Itga2	UTSW	13	114,993,186 (GRCm39)	splice site	probably benign
R0688:Itga2	UTSW	13	114,976,090 (GRCm39)	missense	probably benign	0.00
R0704:Itga2	UTSW	13	114,998,911 (GRCm39)	missense	possibly damaging	0.91
R0760:Itga2	UTSW	13	114,996,168 (GRCm39)	missense	possibly damaging	0.63
R0811:Itga2	UTSW	13	115,007,150 (GRCm39)	missense	possibly damaging	0.92
R0812:Itga2	UTSW	13	115,007,150 (GRCm39)	missense	possibly damaging	0.92
R0836:Itga2	UTSW	13	114,993,215 (GRCm39)	missense	probably damaging	0.99
R1196:Itga2	UTSW	13	115,002,691 (GRCm39)	critical splice donor site	probably null
R1546:Itga2	UTSW	13	114,985,956 (GRCm39)	missense	possibly damaging	0.63
R1639:Itga2	UTSW	13	114,993,832 (GRCm39)	missense	probably benign	0.00
R1834:Itga2	UTSW	13	114,993,263 (GRCm39)	missense	probably damaging	1.00
R1834:Itga2	UTSW	13	114,993,262 (GRCm39)	missense	probably damaging	0.98
R2180:Itga2	UTSW	13	114,985,917 (GRCm39)	missense	possibly damaging	0.67
R2190:Itga2	UTSW	13	115,007,141 (GRCm39)	missense	probably benign	0.05
R2518:Itga2	UTSW	13	115,017,578 (GRCm39)	missense	probably damaging	1.00
R3885:Itga2	UTSW	13	115,005,835 (GRCm39)	missense	probably benign	0.35
R3962:Itga2	UTSW	13	114,976,054 (GRCm39)	missense	probably damaging	0.99
R4094:Itga2	UTSW	13	115,007,161 (GRCm39)	missense	probably benign	0.01
R4193:Itga2	UTSW	13	115,023,185 (GRCm39)	nonsense	probably null
R4290:Itga2	UTSW	13	115,002,709 (GRCm39)	missense	probably damaging	0.98
R4459:Itga2	UTSW	13	114,980,019 (GRCm39)	missense	probably damaging	0.97
R4460:Itga2	UTSW	13	114,980,019 (GRCm39)	missense	probably damaging	0.97
R4628:Itga2	UTSW	13	115,014,229 (GRCm39)	missense	probably benign	0.03
R4655:Itga2	UTSW	13	115,009,805 (GRCm39)	missense	probably benign	0.00
R4716:Itga2	UTSW	13	114,993,909 (GRCm39)	missense	probably damaging	0.98
R4896:Itga2	UTSW	13	114,990,302 (GRCm39)	nonsense	probably null
R5093:Itga2	UTSW	13	114,992,717 (GRCm39)	missense	probably benign	0.00
R5488:Itga2	UTSW	13	114,979,971 (GRCm39)	missense	probably damaging	1.00
R5489:Itga2	UTSW	13	114,979,971 (GRCm39)	missense	probably damaging	1.00
R5743:Itga2	UTSW	13	115,021,042 (GRCm39)	missense	probably damaging	1.00
R5767:Itga2	UTSW	13	114,976,106 (GRCm39)	missense	possibly damaging	0.88
R5790:Itga2	UTSW	13	115,004,742 (GRCm39)	missense	probably benign	0.02
R5923:Itga2	UTSW	13	115,021,055 (GRCm39)	missense	probably benign	0.02
R6163:Itga2	UTSW	13	115,002,726 (GRCm39)	missense	probably damaging	1.00
R6227:Itga2	UTSW	13	114,976,097 (GRCm39)	missense	probably benign	0.30
R6278:Itga2	UTSW	13	114,982,424 (GRCm39)	missense	probably benign	0.05
R6283:Itga2	UTSW	13	115,005,786 (GRCm39)	missense	probably damaging	1.00
R6332:Itga2	UTSW	13	114,980,009 (GRCm39)	missense	probably benign
R6510:Itga2	UTSW	13	115,009,816 (GRCm39)	missense	probably damaging	1.00
R6742:Itga2	UTSW	13	114,973,061 (GRCm39)	missense	possibly damaging	0.93
R6869:Itga2	UTSW	13	115,012,073 (GRCm39)	splice site	probably null
R7073:Itga2	UTSW	13	114,996,149 (GRCm39)	missense	probably damaging	1.00
R7111:Itga2	UTSW	13	115,037,066 (GRCm39)	missense	unknown
R7236:Itga2	UTSW	13	115,014,227 (GRCm39)	missense	probably benign
R7269:Itga2	UTSW	13	115,023,225 (GRCm39)	nonsense	probably null
R7296:Itga2	UTSW	13	114,993,930 (GRCm39)	splice site	probably null
R7350:Itga2	UTSW	13	114,973,738 (GRCm39)	missense	probably damaging	0.98
R7375:Itga2	UTSW	13	115,005,753 (GRCm39)	missense	probably benign	0.06
R7501:Itga2	UTSW	13	115,012,095 (GRCm39)	missense	probably damaging	1.00
R7687:Itga2	UTSW	13	115,002,796 (GRCm39)	missense	probably damaging	1.00
R7766:Itga2	UTSW	13	114,990,427 (GRCm39)	missense	probably benign
R7810:Itga2	UTSW	13	115,002,715 (GRCm39)	missense	probably benign	0.15
R8038:Itga2	UTSW	13	114,990,291 (GRCm39)	missense	probably damaging	1.00
R8948:Itga2	UTSW	13	115,009,866 (GRCm39)	missense	probably damaging	1.00
R9132:Itga2	UTSW	13	115,014,298 (GRCm39)	nonsense	probably null
R9153:Itga2	UTSW	13	115,001,941 (GRCm39)	missense	probably benign	0.00
R9159:Itga2	UTSW	13	115,014,298 (GRCm39)	nonsense	probably null
R9651:Itga2	UTSW	13	115,020,991 (GRCm39)	missense	probably benign	0.00
R9652:Itga2	UTSW	13	115,020,991 (GRCm39)	missense	probably benign	0.00
R9653:Itga2	UTSW	13	115,020,991 (GRCm39)	missense	probably benign	0.00
Z1088:Itga2	UTSW	13	114,993,868 (GRCm39)	missense	possibly damaging	0.46
Z1177:Itga2	UTSW	13	114,990,237 (GRCm39)	critical splice donor site	probably null

Protein Function and Prediction

Integrins are receptors that transduce signals from the extracellular matrix to the cell, regulating adhesion, migration, differentiation, and apoptosis (1). Alpha2 integrin mediates interactions with collagens of the skin to provide a scaffold for cell adhesion (2). Alpha2 integrins are involved in the formation of collagen fibrils (3), the contraction of collagen matrices (4), and the induction of collagenase activity (4) during matrix remodeling.

Expression/Localization

Integrins are localized at focal adhesions (5).

Background

Patients with mutations in ITGA2 demonstrated glycoprotein Ia deficiency [alternatively, Bleeding Disorder, Platelet-type, 9; OMIM %614200; (6)]. The patients are described as having a hemorrhagic disorder and an excessively long bleeding time (6). Platelets from patients with this disorder exhibit almost complete absence of adherence to subendothelium and to purified human collagen type III (7).

Itga2^{tm1.1Eck/ tm1.1Eck}; MGI: 2675420

B6.129P2-Itga2^tm1.1Eck

Researchers determined that Itga2 is required for the adherence of keratinocytes and fibroblasts to collagen I and IV in culture (1). Furthermore, fibroblast from mutant mice had delayed contraction (1).

Itga2^{tm1.1Eck/ tm1.1Eck}; MGI: 2675420

involves: 129P2/OlaHsd

In this genetic background, it was determined that Itga2 mice do not have the normal number of platelets (8). Furthermore, the loss if Itga2 resulted in delayed and decreased aggregation of platelets in response to type I collagen (8).

Itga2^{tm1Ztr/ tm1Ztr}; MGI:2183401

involves: 129S1/Sv * 129X1/SvJ

In this model, there is reduced platelet adhesion to collagen (9).

Itga2^{tm1Ztr/ tm1Ztr}; MGI:2183401

129S1/Sv * 129X1/SvJ * C57BL/6

In this genetic background, it was determined that the branching complexity is markedly diminished in the mammary duct (10). Furthermore, platelets from the mutant mice failed to adhere to type I collagen and had decreased rate of aggregation; wound repair was normal (10).

References

1. Zhang, Z. G., Bothe, I., Hirche, F., Zweers, M., Gullberg, D., Pfitzer, G., Krieg, T., Eckes, B., and Aumailley, M. (2006) Interactions of Primary Fibroblasts and Keratinocytes with Extracellular Matrix Proteins: Contribution of alpha2beta1 Integrin. J Cell Sci. 119, 1886-1895.

2. Wayner, E. A., and Carter, W. G. (1987) Identification of Multiple Cell Adhesion Receptors for Collagen and Fibronectin in Human Fibrosarcoma Cells Possessing Unique Alpha and Common Beta Subunits. J Cell Biol. 105, 1873-1884.

3. Klein, C. E., Dressel, D., Steinmayer, T., Mauch, C., Eckes, B., Krieg, T., Bankert, R. B., and Weber, L. (1991) Integrin Alpha 2 Beta 1 is Upregulated in Fibroblasts and Highly Aggressive Melanoma Cells in Three-Dimensional Collagen Lattices and Mediates the Reorganization of Collagen I Fibrils. J Cell Biol. 115, 1427-1436.

4. Schiro, J. A., Chan, B. M., Roswit, W. T., Kassner, P. D., Pentland, A. P., Hemler, M. E., Eisen, A. Z., and Kupper, T. S. (1991) Integrin Alpha 2 Beta 1 (VLA-2) Mediates Reorganization and Contraction of Collagen Matrices by Human Cells. Cell. 67, 403-410.

5. Humphries, M. J., Travis, M. A., Clark, K., and Mould, A. P. (2004) Mechanisms of Integration of Cells and Extracellular Matrices by Integrins. Biochem Soc Trans. 32, 822-825.

6. Nieuwenhuis, H. K., Akkerman, J. W., Houdijk, W. P., and Sixma, J. J. (1985) Human Blood Platelets Showing no Response to Collagen Fail to Express Surface Glycoprotein Ia. Nature. 318, 470-472.

7. Nieuwenhuis, H. K., Sakariassen, K. S., Houdijk, W. P., Nievelstein, P. F., and Sixma, J. J. (1986) Deficiency of Platelet Membrane Glycoprotein Ia Associated with a Decreased Platelet Adhesion to Subendothelium: A Defect in Platelet Spreading. Blood. 68, 692-695.

8. Holtkotter, O., Nieswandt, B., Smyth, N., Muller, W., Hafner, M., Schulte, V., Krieg, T., and Eckes, B. (2002) Integrin Alpha 2-Deficient Mice Develop Normally, are Fertile, but Display Partially Defective Platelet Interaction with Collagen. J Biol Chem. 277, 10789-10794.

9. Chen, H., Zou, Z., Sarratt, K. L., Zhou, D., Zhang, M., Sebzda, E., Hammer, D. A., and Kahn, M. L. (2006) In Vivo beta1 Integrin Function Requires Phosphorylation-Independent Regulation by Cytoplasmic Tyrosines. Genes Dev. 20, 927-932.

10. Chen, J., Diacovo, T. G., Grenache, D. G., Santoro, S. A., and Zutter, M. M. (2002) The Alpha(2) Integrin Subunit-Deficient Mouse: A Multifaceted Phenotype Including Defects of Branching Morphogenesis and Hemostasis. Am J Pathol. 161, 337-344.

Posted On

2012-10-05

Science Writer

Anne Murray