ICAM4

protein-coding

intercellular adhesion molecule 4 (Landsteiner-Wiener blood group), the group of CD molecules|Ig-like cell adhesion molecule family|Immunoglobulin like domain containing|Blood group antigens

Gene summary

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=LW(A) and Arg-100=LW(B). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_001544.5

Inheritance

ClinVar variants

U:46B:14

Top phenotype

Blood group, Landsteiner-Wiener

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr19:10,286,955-10,288,522

External References & Databases

Ensembl (ENSG00000105371)

Transcript & Mutation Effects

hg38 • Region Span ~1.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, Landsteiner-WienerBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 7632968; 8639917

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ICAM4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

Landsteiner-Wiener phenotypeTotal: 3

not providedTotal: 1

ICAM4-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001544.5. 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			2 clinvar	10 clinvar		12
missense			43 clinvar	4 clinvar		47
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	14	0	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001544.5	RefSeq	NP_001535.1	3	MANE Select
ENST00000380770.5	Ensembl	ENSP00000370147.2	3	MANE Select
NM_001039132.3	RefSeq	NP_001034221.1	3	Standard
ENST00000340992.4	Ensembl	ENSP00000342114.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrin cell surface interactions
Extracellular matrix organization
Immune System
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Adaptive Immune System

Biological Process

cell adhesion
extracellular matrix organization
regulation of immune response
cell-cell adhesion

Molecular Function

integrin binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340992
Coding exons: 3
Length: 1556
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125742
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.405	151	166	0.912	0.00000927	1715
Missense (PolyPhen)		23	35.334	0.65093		337
Synonymous	1.11	58	69.8	0.831	0.00000382	609
Loss of Function	-0.0197	9	8.94	1.01	4.89e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.0010	0.0010	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:11435317}.;

Intolerance Scores

LoFtool: 0.823
RVIS EVS: 0.31
RVIS percentile EVS: 72.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

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