CADM4 cell adhesion molecule 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CADM4provided by HGNC
Official Full Name: cell adhesion molecule 4provided by HGNC
Primary source: HGNC:HGNC:30825
See related: Ensembl:ENSG00000105767 MIM:609744; AllianceGenome:HGNC:30825
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NECL4; TSLL2; IGSF4C; Necl-4; synCAM4
Summary: Enables vascular endothelial growth factor receptor 2 binding activity. Involved in several processes, including negative regulation of protein phosphorylation; regulation of Rac protein signal transduction; and regulation of wound healing. Located in cell leading edge and cell-cell contact zone. [provided by Alliance of Genome Resources, Jul 2025]
Expression: Biased expression in brain (RPKM 59.7), kidney (RPKM 14.7) and 8 other tissues See more
Orthologs: all
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Genomic context

Location:: 19q13.31

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (43622368..43641984, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (46444027..46463643, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (44126520..44144002, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cell adhesion molecule 4 suppresses cell growth and metastasis by inhibiting the Akt signaling pathway in non-small cell lung cancer.
Title: Cell adhesion molecule 4 suppresses cell growth and metastasis by inhibiting the Akt signaling pathway in non-small cell lung cancer.
There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas, but no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas
Title: Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.
Low CADM4 expression is associated with bone marrow metastasis in neuroblastoma.
Title: Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression.
The results suggest that Necl-4 enhances VEGF-induced activation of PLCgamma-c-Raf-MEK-ERK pathway without affecting the phosphorylation and internalization of VEGFR2.
Title: Necl-4 enhances the PLCγ-c-Raf-MEK-ERK pathway without affecting internalization of VEGFR2.
Necl-4 serves as a novel regulator for contact inhibition of cell movement and proliferation cooperatively with the VEGF receptor and PTPN13
Title: The Cell Adhesion Molecule Necl-4/CADM4 Serves as a Novel Regulator for Contact Inhibition of Cell Movement and Proliferation.
results indicate that Necl-4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly
Title: Interaction of Necl-4/CADM4 with ErbB3 and integrin α6 β4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly.
Loss or decrease of CADM4 expression seems to play an important role in breast cancer invasiveness, and it is associated with poorer biological parameters.
Title: Clinicopathological significance of CADM4 expression in invasive ductal carcinoma of the breast.
Cadm4 regulates the growth of the myelin unit and the organization of the underlying axonal membrane.
Title: Genetic deletion of Cadm4 results in myelin abnormalities resembling Charcot-Marie-Tooth neuropathy.
CADM4, as well as 4.1B is expressed specifically in human proximal tubules.
Title: Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S832 (e-PCR)
- UniSTS:72994

RH48989 (e-PCR)
- UniSTS:29794

IGSF4C__6451 (e-PCR)
- UniSTS:468478

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor 1 binding	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor 2 binding	IBA Inferred from Biological aspect of Ancestor more info
enables vascular endothelial growth factor receptor 2 binding	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor 2 binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in central nervous system myelination	IEA Inferred from Electronic Annotation more info
involved_in central nervous system myelination	ISS Inferred from Sequence or Structural Similarity more info
involved_in homophilic cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of peptidyl-threonine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of peptidyl-tyrosine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of vascular endothelial growth factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of vascular endothelial growth factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in oligodendrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of Rac protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of Rac protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell motility	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell motility	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of wound healing	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of wound healing	IEA Inferred from Electronic Annotation more info
involved_in regulation of wound healing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in Golgi membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cell leading edge	IDA Inferred from Direct Assay more info	PubMed
is_active_in cell-cell contact zone	IBA Inferred from Biological aspect of Ancestor more info
located_in cell-cell contact zone	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cell adhesion molecule 4

Names: TSLC1-like 2; TSLC1-like protein 2; immunoglobulin superfamily member 4C; nectin-like 4; nectin-like protein 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_145296.2 → NP_660339.1 cell adhesion molecule 4 precursor

See identical proteins and their annotated locations for NP_660339.1

Status: VALIDATED

Source sequence(s)

AC005525, AF363368

Consensus CDS

CCDS12627.1

UniProtKB/Swiss-Prot

B2R7L5, Q8NFZ8, Q9Y4A4

Related

ENSP00000222374.1, ENST00000222374.3

Conserved Domains (5) summary

smart00294
Location:344 → 362

4.1m; putative band 4.1 homologues' binding motif

pfam13927
Location:224 → 295

Ig_3; Immunoglobulin domain

cd00096
Location:30 → 36

Ig; Ig strand A' [structural motif]

cd05885
Location:121 → 220

IgI_2_Necl-4; Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains

cl11960
Location:29 → 120

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

43622368..43641984 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017026452.1 → XP_016881941.1 cell adhesion molecule 4 isoform X1

Conserved Domains (5) summary

smart00294
Location:325 → 343

4.1m; putative band 4.1 homologues' binding motif

cd05885
Location:121 → 201

Ig2_Necl-4; Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4, also known as cell adhesion molecule 4 (CADM4))

smart00408
Location:218 → 279

IGc2; Immunoglobulin C-2 Type

smart00410
Location:212 → 289

IG_like; Immunoglobulin like

cl11960
Location:10 → 101

Ig; Immunoglobulin domain
XM_005258620.3 → XP_005258677.1 cell adhesion molecule 4 isoform X2

Related

ENSP00000574214.1, ENST00000904155.1

Conserved Domains (4) summary

pfam13927
Location:224 → 295

Ig_3; Immunoglobulin domain

cd00096
Location:30 → 36

Ig; Ig strand A' [structural motif]

cd05885
Location:121 → 220

IgI_2_Necl-4; Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains

cl11960
Location:29 → 120

Ig; Immunoglobulin domain
XM_047438387.1 → XP_047294343.1 cell adhesion molecule 4 isoform X3