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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ICAM4 Gene

protein-coding GIFtS: 56
GCID: GC19P010397

intercellular adhesion molecule 4 (Landsteiner-Wiener blood...

(Previous names: intercellular adhesion molecule 4, Landsteiner-Wiener blood...)
(Previous symbol: LW)

Explore 7 diseases affiliated with
ICAM4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Intercellular Adhesion Molecule 4 (Landsteiner-Wiener Blood Group)¹ ²		LW Blood Group Protein² ³
LW¹ ² ³		Intercellular Adhesion Molecule 4, Landsteiner-Wiener Blood Group¹
CD242¹ ²		Landsteiner-Wiener Blood Group¹
Intercellular Adhesion Molecule 4 (LW Blood Group)¹ ²		Intercellular Adhesion Molecule 4²
CD242 Antigen² ³		Landsteiner-Wiener Blood Group Antigen A²
Landsteiner-Wiener Blood Group Glycoprotein² ³		ICAM-4³

External Ids:	HGNC: 5347¹	Entrez Gene: 3386²	Ensembl: ENSG00000105371⁷	OMIM: 614088⁵	UniProtKB: Q14773³

Export aliases for ICAM4 gene to outside databases

Previous GC identifers: GC19P010519 GC19P010620 GC19P010242 GC19P010258 GC19P009977

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ICAM4:

This gene encodes the Landsteiner-Wiener (LW) blood group antigen(s) that belongs to the immunoglobulin (Ig)

superfamily, and that shares similarity with the intercellular adhesion molecule (ICAM) protein family. This ICAM

protein contains 2 Ig-like C2-type domains and binds to the leukocyte adhesion LFA-1 protein. The molecular basis of

the LW(A)/LW(B) blood group antigens is a single aa variation at position 100; Gln-100

UniProtKB/Swiss-Prot: ICAM4_HUMAN, Q14773

Function: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a

ligand for alpha-4/beta-1 and alpha-V integrins

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011295.11

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the ICAM4 gene promoter:
GR STAT1 AP-2alpha isoform 3 AP-2alpha isoform 2 STAT1alpha AP-2alpha isoform 4 GR-alpha AP-2alpha AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: ICAM4 promoter sequence

Search SABiosciences Chromatin IP Primers for ICAM4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ICAM4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.2-cen Ensembl cytogenetic band: 19p13.2 HGNC cytogenetic band: 19p13.2-cen

ICAM4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ICAM4 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19P010397: view genomic region (about GC identifiers)

Start:	10,397,643 bp from pter	End:	10,399,198 bp from pter
Size:	1,556 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: ICAM4_HUMAN, Q14773 (See protein sequence)

Recommended Name: Intercellular adhesion molecule 4 precursor

Size: 271 amino acids; 29265 Da

Subcellular location: Isoform Long: Cell membrane; Single-pass type I membrane protein

Subcellular location: Isoform Short: Secreted

Secondary accessions: A0M8X2 Q14771 Q14772 Q16375 Q9BWR0

Alternative splicing: 3 isoforms: Q14773-1 Q14773-2 Q14773-3

Explore the universe of human proteins at neXtProt for ICAM4: NX_Q14773

Post-translational modifications:

N- and O-glycosylated¹

View neXtProt modification sites for NX_Q14773

ICAM4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_001034221.1 NP_001535.1 NP_071772.1

ENSEMBL proteins:

ENSP00000370147 ENSP00000342114 ENSP00000377320

Reactome Protein details: Q14773
Human Recombinant Protein Products for ICAM4:

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	Uscn Proteins for ICAM4

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0016021	integral to membrane	IEA	--

ICAM4 for ontologies About GeneDecksing

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(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ICAM4 for domains About GeneDecksing

3 InterPro domains/families:

IPR013768 ICAM_N

IPR013783 Ig-like_fold

IPR003987 ICAM_VCAM_N

Graphical View of Domain Structure for InterPro Entry Q14773

ProtoNet protein and cluster: Q14773

2 Blocks protein families:

IPB003987 Intercellular adhesion molecule/vascular cell adhesion molecule-1 signature

IPB013768 Intercellular adhesion molecule

UniProtKB/Swiss-Prot: ICAM4_HUMAN, Q14773

Similarity: Belongs to the immunoglobulin superfamily. ICAM family

Similarity: Contains 2 Ig-like C2-type (immunoglobulin-like) domains

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: ICAM4_HUMAN, Q14773

Function: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a

ligand for alpha-4/beta-1 and alpha-V integrins

Genatlas biochemistry entry for ICAM4:

adhesion molecule,intercellular 4

Gene Ontology (GO): 1 molecular function term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005178	integrin binding	TAS	8566017

ICAM4 for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for ICAM4:

Increased gamma-H2AX phosphory

1 MGI mutant phenotype (inferred from 1 allele) (MGI details for Icam4):

hematopoietic system

ICAM4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-out Icam4^tm1Jach for ICAM4

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for ICAM4

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ICAM4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Immune System

Immune System

1.00

Adaptive Immune System

0.59

Signaling by GPCR

Signal Transduction

0.56

ECM-receptor interaction

Integrin cell surface interactions

0.32

Cleavage of Alpha-1-Microglobulin

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

0.30

Pathway sources
See GeneCards unified pathways
Show all pathways

5 Reactome Pathways for ICAM4

	Integrin cell surface interactions
	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
	Signal Transduction
	Adaptive Immune System
	Immune System

ICAM4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for ICAM4

STRING Interaction Network Preview (showing 5 interactants - click image to see 8)

5/10 Interacting proteins for ICAM4 (Q14773³ ENSP00000342114⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 10)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ITGAV	P06756³, ENSP00000261023⁴	I2D: score=1 STRING: ENSP00000261023
ITGB2	P05107³, ENSP00000303242⁴	I2D: score=1 STRING: ENSP00000303242
RHAG	Q02094³, ENSP00000360217⁴	I2D: score=1 STRING: ENSP00000360217
ITGAL	P20701³, ENSP00000349252⁴	I2D: score=1 STRING: ENSP00000349252
ITGA4	P13612³, ENSP00000380227⁴	I2D: score=1 STRING: ENSP00000380227

About this table

Gene Ontology (GO): 2 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0016337	cell-cell adhesion	IEA	--
GO:0050776	regulation of immune response	TAS	--

ICAM4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for ICAM4
Search CenterWatch for drugs/clinical trials and news about ICAM4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for ICAM4 gene (3 alternative transcripts):

NM_001039132.2 NM_001544.4 NM_022377.3

Unigene Cluster for ICAM4:

Intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)

Hs.706750 [show with all ESTs]

Unigene Representative Sequence: NM_022377

3 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000380770(uc002mns.2) ENST00000340992(uc002mnr.2) ENST00000393717(uc002mnt.2)

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Additional cDNA sequence:

BC000046.2 BC029364.1 BT009816.1 L27670.1 L27671.1

3 DOTS entries:

DT.405584 DT.92418895 DT.102822076

24/282 AceView cDNA sequences (see all 282):

NM_022377 CR617464 BP346334 CB265238 BC029364 AI753618 BQ710223 CB529704

CA309669 BQ940498 BG945719 BI868876 AW069267 BP351585 BU170298 AU279886

BQ683708 BM704729 CB138808 AU099232 CK429562 AA306799 CB529024 BM473834

GeneLoc Exon Structure

2 Alternative Splicing Database (ASD) splice patterns (SP) for ICAM4 About this scheme

ExUns:	1a	·	1b	^	2a	·	2b	^	3a	·	3b
SP1:					-
SP2:

ECgene alternative splicing isoforms for ICAM4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

ICAM4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GTGGCTGACG

About this image

ICAM4 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Embryoid bodies (Generation and expan...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See ICAM4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for ICAM4

SOURCE GeneReport for Unigene cluster: Hs.706750

UniProtKB/Swiss-Prot: ICAM4_HUMAN, Q14773

Tissue specificity: Erythrocytes

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for ICAM4 gene from 1/6 species (see all 6) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
lizard (Anolis carolinensis)	Reptilia	-- ICAM4⁶	--	7(a) 5(a)	many ↔ many many ↔ many	GL344305.1(34371-49910) GL343233.1(1353200-1357090)

ENSEMBL Gene Tree for ICAM4 (if available)
TreeFam Gene Tree for ICAM4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for ICAM4 gene

ICAM2² ICAM5² ICAM1² ICAM3²

ICAM4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: ICAM4_HUMAN, Q14773

Polymorphism: Responsible for the Landsteiner-Wiener blood group system [MIM:111250]. The molecular basis of the

LW(A)=LW5/LW(B)=LW7 blood group antigens is a single variation in position 100; Gln-100 corresponds to LW(A) and

Arg-100 to LW(B)

SNP ID	Valid	Clinical significance	Chr 19 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs77493670^1,2	C,F	non-pathogenic	18573074(+)	`TTACCA/GGCTGC`	6	Q R	mis¹		2	NA EU	5253
rs35713817^1,2	C	--	9977811(+)	`CCCTTC/ATGGGT`	6	/L /F	mis¹		2	NA	4
rs34385135^1,2	C,F,H	--	9978110(+)	`GCTGGA/CAGAGG`	3	--	int¹		6	NS NA	500
rs5030385^1,2	H	--	9978587(+)	`CCACGC/GGGGTC`	3	--	ut3¹ int¹		6	NS EA	510
rs34274798^1,2	C	--	9979398(+)	`CTTATC/GGAGTG`	3	--	ds500¹		5	NS NA WA	216
rs36110042^1,2	C,F	--	9979503(+)	`TCTGAT/CTGGAT`	3	--	ds500¹		5	NS NA WA	216
rs3093029^1,2	C,F	--	9979530(+)	`NNNNCC/GCACCT`	3	--	ds500¹		7	NA NS CSA WA	376
rs34925519^1,2	C	--	9979614(+)	`GGAGTG/TAGACC`	3	--	ds500¹		4	NS NA	98
rs34778003^1,2	C	--	9979641(+)	`GGAGGG/ATCCCA`	3	--	ds500¹		4	NS NA	98
rs141882537^1,2	C	--	10397870(+)	`GCAGCC/TGGGGA`	6	P L	mis¹		1	NA	3796

HapMap Linkage Disequilibrium report for ICAM4 (10397643 - 10399198 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for ICAM4: --
Human Gene Mutation Database (HGMD): ICAM4

Locus Specific Mutation Databases (LSDB): ICAM4
Blood Group Antigen Gene Mutation Database (BGMUT) blood group system

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing ICAM4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

ICAM4 for disorders           About GeneDecksing

OMIM gene information: 614088    OMIM disorders: --

7 diseases for ICAM4:    About MalaCards

sickle cell disease multiple myeloma hepatitis c myeloma

meningioma hepatitis leukemia

Human Genome Epidemiology (HuGE) Navigator: ICAM4 (16 documents)

Export disorders for ICAM4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for ICAM4 gene, integrated from 9 sources (see all 41):
(articles sorted by number of sources associating them with ICAM4)

Utopia: connect your pdf to the dynamic
world of online information

Characterization of the gene encoding the human LW blood group protein in LW+ and LW- phenotypes. (PubMed id 8639917)^{1, 2, 3, 9} Hermand P.... Bailly P. (1996)
The LW blood group glycoprotein is homologous to intercellular adhesion molecules. (PubMed id 8202485)^{1, 2, 9} Bailly P.... Cartron J.-P. (1994)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)- family integrins through novel integrin-binding mechanisms. (PubMed id 11435317)^{1, 2} Spring F.A.... Anstee D.J. (2001)
Molecular basis and expression of the LWa/LWb blood group polymorphism. (PubMed id 7632968)^{1, 2} Hermand P....Bailly P. (1995)
Linkage of the LW blood group locus with the complement C3 and Lutheran blood group loci. (PubMed id 6431896)^{1, 3} Sistonen P. (1984)
Binding sites of leukocyte beta 2 integrins (LFA-1, Mac-1) on the human ICAM-4/LW blood group protein. (PubMed id 10846180)^{1, 9} Hermand P....Bailly P. (2000)
[Polymorphism of LW Blood Group Gene in Chinese Population.] (PubMed id 18549656)^{1, 9} Su Y.Q....Wei T.L. (2008)
Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. (PubMed id 15308566)^{1, 9} Zennadi R....Telen M.J. (2004)
Erythrocyte plasma membrane-bound ERK1/2 activation pr omotes ICAM-4-mediated sickle red cell adhesion to endothelium. (PubMed id 22147898)¹ Zennadi R....Telen M.J. (2012)

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		AND	OR
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 3386	HGNC: 5347	AceView: ICAM1andICAM4	Ensembl:ENSG00000105371	euGenes: HUgn3386
ECgene: ICAM4	H-InvDB: ICAM4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for ICAM4	Pharmacogenomics, SNPs, Pathways
dbRBC/BGMUT	http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=lw
SeattleSNPs	http://pga.gs.washington.edu/data/icam4/

Intellectual Property for ICAM4 gene
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Patent Information for ICAM4 gene:
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