CADM1

cell adhesion molecule 1, the group of V-set domain containing|C2-set domain containing|Nectins and nectin-like molecules

Basic information

Region (hg38): 11:115169218-115504957

Previous symbols: [ "TSLC1", "IGSF4" ]

Links

ENSG00000182985 ∙ NCBI:23705 ∙ OMIM:605686 ∙ HGNC:5951 ∙ Uniprot:Q9BY67 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CADM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CADM1 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				5	5	10
missense			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel				2	1	3
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding						0
Total	0	0	15	8	6

Variants in CADM1

This is a list of pathogenic ClinVar variants found in the CADM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-115176479-T-G		not specified	Uncertain significance (Apr 24, 2024)
11-115178666-C-T			Likely benign (May 09, 2018)
11-115178681-C-G		not specified	Uncertain significance (Nov 21, 2023)
11-115178714-G-C			Likely benign (Jul 07, 2018)
11-115178716-C-T		not specified	Uncertain significance (Mar 26, 2024)
11-115178730-G-A			Uncertain significance (Jun 01, 2024)
11-115209591-ATGGTGGTGG-A			Benign (Jul 01, 2024)
11-115209591-A-ATGG			Likely benign (Dec 06, 2019)
11-115209623-GGTT-G			Likely benign (Apr 01, 2022)
11-115209645-G-A			Likely benign (Aug 20, 2018)
11-115209662-A-G			Likely benign (Aug 21, 2018)
11-115214681-A-G			Benign (Dec 31, 2019)
11-115214699-A-G			Benign (Dec 31, 2019)
11-115214704-T-A		not specified	Uncertain significance (Jul 15, 2021)
11-115214731-C-T		not specified	Uncertain significance (Feb 22, 2023)
11-115217903-G-T			Likely benign (Apr 16, 2018)
11-115217927-C-T			Benign (Dec 01, 2023)
11-115217929-C-T		not specified	Uncertain significance (May 27, 2022)
11-115217942-G-A			Likely benign (Mar 01, 2023)
11-115217963-A-C			Likely benign (Mar 01, 2023)
11-115217997-T-G			Benign (Jun 05, 2018)
11-115229156-C-T			Benign (Dec 31, 2019)
11-115229275-G-A			Benign (Dec 31, 2019)
11-115231371-C-G		not specified	Uncertain significance (Dec 06, 2021)
11-115231386-T-G		not specified	Uncertain significance (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CADM1	protein_coding	protein_coding	ENST00000452722	10	335738

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.662	0.338	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	170	252	0.674	0.0000149	2857
Missense in Polyphen		40	96.111	0.41618		1114
Synonymous	-1.17	123	108	1.14	0.00000741	895
Loss of Function	3.44	4	21.0	0.191	0.00000110	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates homophilic cell-cell adhesion in a Ca(2+)- independent manner. Also mediates heterophilic cell-cell adhesion with CADM3 and NECTIN3 in a Ca(2+)-independent manner. Acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo. May contribute to the less invasive phenotypes of lepidic growth tumor cells. In mast cells, may mediate attachment to and promote communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. Acts as a synaptic cell adhesion molecule and plays a role in the formation of dendritic spines and in synapse assembly (By similarity). May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons. May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa. {ECO:0000250, ECO:0000269|PubMed:11279526, ECO:0000269|PubMed:12050160, ECO:0000269|PubMed:12234973, ECO:0000269|PubMed:12920246, ECO:0000269|PubMed:15811952, ECO:0000269|PubMed:15905536, ECO:0000269|PubMed:22438059}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Splicing factor NOVA regulated synaptic proteins;rac1 cell motility signaling pathway;Cell-cell junction organization;Nectin/Necl trans heterodimerization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.113
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.768
• hipred: Y
• hipred_score: 0.665
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cadm1
• 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; reproductive system phenotype; normal phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: T cell mediated cytotoxicity;apoptotic process;homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;multicellular organism development;spermatogenesis;cell recognition;viral process;cell differentiation;adherens junction organization;susceptibility to natural killer cell mediated cytotoxicity;positive regulation of natural killer cell mediated cytotoxicity;positive regulation of cytokine secretion;activated T cell proliferation;detection of stimulus
• Cellular component: plasma membrane;cell-cell junction;integral component of membrane;basolateral plasma membrane;synapse
• Molecular function: signaling receptor binding;protein binding;PDZ domain binding;protein homodimerization activity