ICAM3

protein-coding

intercellular adhesion molecule 3, the group of Immunoglobulin like domain containing|CD molecules|Ig-like cell adhesion molecule family

Gene summary

The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

MANE transcript

NM_002162.5

Inheritance

—

ClinVar variants

U:80B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.55

Max pathogenic AF

—

Genomic locus

chr19:10,333,776-10,339,661

External References & Databases

Ensembl (ENSG00000076662)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 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 ICAM3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002162.5. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			78 clinvar	6 clinvar	1 clinvar	85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	80	7	2	89

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002162.5	RefSeq	NP_002153.2	7	MANE Select
ENST00000160262.10	Ensembl	ENSP00000160262.3	7	MANE Select
NM_001320605.2	RefSeq	NP_001307534.1	6	Standard
NM_001320606.2	RefSeq	NP_001307535.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Ebola Virus Pathway on Host
Ebola Virus Pathway on Host
Integrin cell surface interactions
CD209 (DC-SIGN) signaling

Biological Process

stimulatory C-type lectin receptor signaling pathway
phagocytosis
cell adhesion
extracellular matrix organization
regulation of immune response

Molecular Function

signaling receptor binding
integrin binding
protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000160262
Coding exons: 7
Length: 6048
Individuals with no LoFs: 125384
Homozygous LoFs: 0
Heterozygous LoFs: 363
Defined: 125747
p: 0.00144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.301	306	321	0.953	0.0000173	3472
Missense (PolyPhen)		82	92.995	0.88176		1063
Synonymous	-0.747	158	147	1.08	0.00000868	1189
Loss of Function	-2.29	31	20.0	1.55	9.99e-7	205

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00088	0.00080	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.0085	0.0085	notable
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.00050	0.00049	rare
South Asian	0.0017	0.0017	notable
Other	0.00068	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2) (PubMed:1448173). ICAM3 is also a ligand for integrin alpha-D/beta-2. In association with integrin alpha-L/beta-2, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). {ECO:0000269|PubMed:1448173, ECO:0000269|PubMed:23775590}.;

Recessive Scores

pRec: 0.187

Intolerance Scores

LoFtool: 0.941
RVIS EVS: -0.04
RVIS percentile EVS: 50.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.294

Gene Damage Prediction

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