CADM1

protein-coding

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

Gene summary

Enables identical protein binding activity and signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TSLC1
IGSF4

MANE transcript

NM_001301043.2

Inheritance

ClinVar variants

U:46B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr11:115,169,218-115,504,957

External References & Databases

Ensembl (ENSG00000182985)

Transcript & Mutation Effects

hg38 • Region Span ~335.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CADM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001301043.2. 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			1 clinvar	5 clinvar	5 clinvar	11
missense			40 clinvar	1 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	46	6	5	57

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001301043.2	RefSeq	NP_001287972.1	12	MANE Select
ENST00000331581.11	Ensembl	ENSP00000329797.6	12	MANE Select
NM_001098517.2	RefSeq	NP_001091987.1	9	Standard
NM_001301044.2	RefSeq	NP_001287973.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

signaling receptor binding
protein binding
PDZ domain binding
protein homodimerization activity

Cellular Component

plasma membrane
cell-cell junction
integral component of membrane
basolateral plasma membrane
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000452722
Coding exons: 10
Length: 335738
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.84	170	252	0.674	0.0000149	2857
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.113
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.875

Gene Damage Prediction

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