ALCAM

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

Basic information

Region (hg38): 3:105366909-105576900

Links

ENSG00000170017 ∙ NCBI:214 ∙ OMIM:601662 ∙ HGNC:400 ∙ Uniprot:Q13740 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALCAM gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALCAM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	5	6
missense			27	1	3	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	27	2	8

Variants in ALCAM

This is a list of pathogenic ClinVar variants found in the ALCAM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-105367431-C-T		not specified	Uncertain significance (Mar 15, 2024)
3-105367436-C-T		not specified	Uncertain significance (Jun 10, 2024)
3-105367463-G-C		not specified	Uncertain significance (Apr 08, 2024)
3-105520057-T-TC			Benign (Jan 17, 2024)
3-105520086-A-C			Likely benign (Dec 01, 2022)
3-105520133-T-C		not specified	Uncertain significance (Dec 08, 2023)
3-105524357-C-T			Benign (May 21, 2018)
3-105524359-A-T		not specified	Uncertain significance (May 09, 2023)
3-105524365-C-T			Benign (Dec 31, 2019)
3-105524383-T-C		not specified	Uncertain significance (Mar 06, 2023)
3-105524412-A-G		not specified	Uncertain significance (Feb 07, 2023)
3-105524499-A-C		not specified	Uncertain significance (Feb 16, 2023)
3-105532040-T-C		not specified	Uncertain significance (Jan 22, 2024)
3-105532040-T-G		not specified	Uncertain significance (May 04, 2022)
3-105533611-C-G		not specified	Uncertain significance (Nov 28, 2023)
3-105533623-A-C		not specified	Uncertain significance (Mar 30, 2024)
3-105533637-A-T		not specified	Uncertain significance (Mar 04, 2024)
3-105533648-A-G		not specified	Uncertain significance (Dec 21, 2022)
3-105534663-C-T		not specified	Likely benign (Dec 01, 2022)
3-105534677-T-C		not specified	Uncertain significance (Jan 23, 2024)
3-105534684-A-G		not specified	Uncertain significance (May 18, 2023)
3-105534695-C-T		not specified	Uncertain significance (Oct 10, 2023)
3-105534718-G-A		not specified	Uncertain significance (Mar 30, 2024)
3-105534771-C-G		not specified	Uncertain significance (Jul 13, 2021)
3-105534776-T-A		not specified	Uncertain significance (Nov 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALCAM	protein_coding	protein_coding	ENST00000306107	15	209992

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.733	0.267	125730	0	12	125742	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.993	260	309	0.841	0.0000149	3820
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000105	0.0000992
East Asian	0.0000548	0.0000544
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.0000629	0.0000615
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000688	0.0000653
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.365

Intolerance Scores

• loftool: 0.433
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.3

Haploinsufficiency Scores

• pHI: 0.733
• hipred: Y
• hipred_score: 0.654
• ghis: 0.473

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.947

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alcam
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Zebrafish Information Network

• Gene name: alcama
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: adaptive immune response;cell adhesion;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;signal transduction;motor neuron axon guidance;retinal ganglion cell axon guidance;axon extension involved in axon guidance;neuron projection extension
• Cellular component: immunological synapse;integral component of plasma membrane;focal adhesion;external side of plasma membrane;axon;dendrite;intrinsic component of plasma membrane;T cell receptor complex;neuronal cell body;extracellular exosome
• Molecular function: signaling receptor binding;protein binding;identical protein binding