ITGAL

protein-coding

integrin subunit alpha L, the group of Integrin alpha subunits|CD molecules|MicroRNA protein coding host genes

Gene summary

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

CD11A

MANE transcript

NM_002209.3

Inheritance

—

ClinVar variants

U:95B:18

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr16:30,472,658-30,523,567

External References & Databases

Ensembl (ENSG00000005844)

Transcript & Mutation Effects

hg38 • Region Span ~50.9 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 ITGAL variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 9

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002209.3. 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	3 clinvar	7
missense			94 clinvar	11 clinvar	1 clinvar	106
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	95	14	4	113

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002209.3	RefSeq	NP_002200.2	31	MANE Select
ENST00000356798.11	Ensembl	ENSP00000349252.5	31	MANE Select
NM_001114380.2	RefSeq	NP_001107852.1	29	Standard
ENST00000358164.10	Ensembl	ENSP00000350886.5	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Viral myocarditis - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Malaria - Homo sapiens (human)

Biological Process

T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
phagocytosis
inflammatory response
cell adhesion
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules

Molecular Function

protein binding
ICAM-3 receptor activity
protein-containing complex binding
metal ion binding
protein heterodimerization activity

Cellular Component

plasma membrane
integrin complex
cell surface
membrane
integrin alphaL-beta2 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356798
Coding exons: 31
Length: 50528
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.18	521	681	0.765	0.0000386	7653
Missense (PolyPhen)		87	167.85	0.51832		1835
Synonymous	0.792	267	284	0.940	0.0000173	2324
Loss of Function	5.29	17	62.0	0.274	0.00000297	703

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin alpha-L/beta-2 is also a receptor for F11R (PubMed:11812992, PubMed:15528364). Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992). Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis (By similarity). Integrin alpha-L/beta-2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). {ECO:0000250|UniProtKB:P24063, ECO:0000269|PubMed:11812992, ECO:0000269|PubMed:15356110, ECO:0000269|PubMed:15528364, ECO:0000269|PubMed:23775590}.;

Recessive Scores

pRec: 0.421

Intolerance Scores

LoFtool: 0.374
RVIS EVS: -0.86
RVIS percentile EVS: 10.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.871

Gene Damage Prediction

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