ICAM1

protein-coding

intercellular adhesion molecule 1, the group of Receptor ligands|Immunoglobulin like domain containing|CD molecules|Ig-like cell adhesion molecule family

Gene summary

This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000201.3

Inheritance

—

ClinVar variants

U:73B:21

Top phenotype

ICAM1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr19:10,271,093-10,286,615

External References & Databases

Ensembl (ENSG00000090339)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 kb

Loading mutation effect viewer...

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 ICAM1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 16

ICAM1-related disorderTotal: 8

Malaria, susceptibility toTotal: 5

Malaria, cerebral, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000201.3. 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			3 clinvar	7 clinvar	4 clinvar	14
missense			68 clinvar	8 clinvar	2 clinvar	78
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	73	15	6	94

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000201.3	RefSeq	NP_000192.2	7	MANE Select
ENST00000264832.8	Ensembl	ENSP00000264832.2	7	MANE Select
ENST00000423829.2	Ensembl	ENSP00000413124.2	5	Standard
ENST00000423829.3	Ensembl	ENSP00000413124.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
Viral myocarditis - Homo sapiens (human)
Influenza A - Homo sapiens (human)

Biological Process

ovarian follicle development
regulation of leukocyte mediated cytotoxicity
response to amphetamine
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
acute inflammatory response to antigenic stimulus

Molecular Function

virus receptor activity
transmembrane signaling receptor activity
integrin binding
protein binding
signaling receptor activity

Cellular Component

immunological synapse
extracellular space
plasma membrane
integral component of plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264832
Coding exons: 7
Length: 15781
Individuals with no LoFs: 125633
Homozygous LoFs: 0
Heterozygous LoFs: 115
Defined: 125748
p: 0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0190	322	323	0.997	0.0000201	3346
Missense (PolyPhen)		83	99.352	0.83542		1085
Synonymous	-0.0937	150	149	1.01	0.00000944	1200
Loss of Function	2.79	6	19.2	0.313	9.75e-7	214

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.0047	0.0046	notable
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans- endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. {ECO:0000269|PubMed:11173916, ECO:0000269|PubMed:17875742}.; FUNCTION: (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. {ECO:0000269|PubMed:11160747, ECO:0000269|PubMed:16004874, ECO:0000269|PubMed:9539703}.;

Intolerance Scores

LoFtool: 0.605
RVIS EVS: 0.25
RVIS percentile EVS: 69.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.439

Gene Damage Prediction

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