ALCAM

protein-coding

activated leukocyte cell adhesion molecule, the group of V-set domain containing|CD molecules|C2-set domain containing|Ig-like cell adhesion molecule family

Gene summary

This gene encodes activated leukocyte cell adhesion molecule (ALCAM), also known as CD166 (cluster of differentiation 166), which is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain. This protein binds to T-cell differentiation antigene CD6, and is implicated in the processes of cell adhesion and migration. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001627.4

Inheritance

—

ClinVar variants

U:76B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr3:105,366,909-105,576,900

External References & Databases

Ensembl (ENSG00000170017)

Transcript & Mutation Effects

hg38 • Region Span ~210.0 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 ALCAM variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001627.4. 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	6 clinvar	3 clinvar	11
missense			68 clinvar	3 clinvar	2 clinvar	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	76	9	5	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001627.4	RefSeq	NP_001618.2	15	MANE Select
ENST00000306107.9	Ensembl	ENSP00000305988.5	15	MANE Select
NM_001243280.2	RefSeq	NP_001230209.1	14	Standard
NM_001243281.2	RefSeq	NP_001230210.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
alcama	Danio rerio	Structure: retinal ganglion cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

alcama

Danio rerio

Structure: retinal ganglion cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Developmental Biology
L1CAM interactions
Axon guidance

Biological Process

adaptive immune response
cell adhesion
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
signal transduction
motor neuron axon guidance

Molecular Function

signaling receptor binding
protein binding
identical protein binding

Cellular Component

immunological synapse
integral component of plasma membrane
focal adhesion
external side of plasma membrane
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306107
Coding exons: 15
Length: 209992
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125742
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.993	260	309	0.841	0.0000149	3820
Missense (PolyPhen)		44	76.115	0.57807		964
Synonymous	0.140	113	115	0.983	0.00000634	1089
Loss of Function	4.13	6	30.7	0.195	0.00000137	408

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000069	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:7760007, PubMed:15496415, PubMed:15048703, PubMed:16352806, PubMed:23169771, PubMed:24945728). Promotes T-cell activation and proliferation via its interactions with CD6 (PubMed:15048703, PubMed:16352806, PubMed:24945728). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (PubMed:15294938, PubMed:16352806). Mediates homotypic interactions with cells that express ALCAM (PubMed:15496415, PubMed:16352806). Required for normal hematopoietic stem cell engraftment in the bone marrow (PubMed:24740813). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction (PubMed:23169771). Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions (PubMed:15496415, PubMed:23169771). Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons (By similarity). {ECO:0000250|UniProtKB:P42292, ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:15496415, ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:24945728, ECO:0000269|PubMed:7760007}.;

Recessive Scores

pRec: 0.365

Intolerance Scores

LoFtool: 0.433
RVIS EVS: 0.2
RVIS percentile EVS: 67.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.947

Gene Damage Prediction

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