CADM2

Summary

CADM2 (cell adhesion molecule 2, HGNC:29849) is a protein-coding gene on chromosome 3p12.1, encoding Cell adhesion molecule 2 (Q8N3J6). Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation.

This gene encodes a member of the synaptic cell adhesion molecule 1 (SynCAM) family which belongs to the immunoglobulin (Ig) superfamily. The encoded protein has three Ig-like domains and a cytosolic protein 4.1 binding site near the C-terminus. Proteins belonging to the protein 4.1 family crosslink spectrin and interact with other cytoskeletal proteins. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 253559 — RefSeq curated summary.

At a glance

• GWAS associations: 195
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_001167675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29849
Approved symbol	CADM2
Name	cell adhesion molecule 2
Location	3p12.1
Locus type	gene with protein product
Status	Approved
Aliases	NECL3, Necl-3, SynCAM2, SynCAM-2
Ensembl gene	ENSG00000175161
Ensembl biotype	protein_coding
OMIM	609938
Entrez	253559

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000383699, ENST00000405615, ENST00000407528, ENST00000473523, ENST00000485126

RefSeq mRNA: 14 — MANE Select: NM_001167675 NM_001167674, NM_001167675, NM_001256502, NM_001256503, NM_001256504, NM_001256505, NM_001375960, NM_001375961, NM_001375964, NM_001375967, NM_001375968, NM_001381963, NM_001381964, NM_153184

CCDS: CCDS33792, CCDS54613, CCDS54614

Canonical transcript exons

ENST00000383699 — 10 exons

Exon	Start	End
ENSE00001210295	86065605	86065730
ENSE00001210297	85961469	85961647
ENSE00001210300	85935767	85935857
ENSE00001210307	85912373	85912543
ENSE00001210310	85886190	85886327
ENSE00001210316	85883291	85883443
ENSE00001252725	85802047	85802196
ENSE00001498178	86066665	86074429
ENSE00001557363	85726522	85726548
ENSE00001826415	84958989	84959668

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 27.4998 / max 1394.4374, expressed in 625 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37416	26.6373	578
37417	0.6065	180
37425	0.1177	38
37432	0.1019	7
37415	0.0364	19

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.71	gold quality
medial globus pallidus	UBERON:0002477	96.98	gold quality
substantia nigra pars compacta	UBERON:0001965	96.71	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.47	gold quality
sural nerve	UBERON:0015488	96.46	gold quality
globus pallidus	UBERON:0001875	96.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.42	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.21	gold quality
superior frontal gyrus	UBERON:0002661	95.74	gold quality
primary visual cortex	UBERON:0002436	95.61	gold quality
occipital lobe	UBERON:0002021	95.40	gold quality
postcentral gyrus	UBERON:0002581	95.34	gold quality
entorhinal cortex	UBERON:0002728	95.25	gold quality
parietal lobe	UBERON:0001872	95.23	gold quality
lateral globus pallidus	UBERON:0002476	94.50	gold quality
cerebellar vermis	UBERON:0004720	93.79	gold quality
pons	UBERON:0000988	93.43	gold quality
prefrontal cortex	UBERON:0000451	93.28	gold quality
cortical plate	UBERON:0005343	93.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.37	gold quality
middle temporal gyrus	UBERON:0002771	92.35	gold quality
frontal cortex	UBERON:0001870	92.21	gold quality
cerebral cortex	UBERON:0000956	91.99	gold quality
temporal lobe	UBERON:0001871	91.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.83	gold quality
neocortex	UBERON:0001950	91.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.62	gold quality
Ammon’s horn	UBERON:0001954	91.08	gold quality
superior vestibular nucleus	UBERON:0007227	90.35	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	4433.42
E-MTAB-11268	yes	1699.15
E-GEOD-93593	yes	680.57
E-MTAB-9435	yes	346.16
E-GEOD-135922	yes	20.66
E-HCAD-5	yes	16.88
E-GEOD-137537	yes	15.05
E-ANND-3	yes	11.11
E-GEOD-180759	no	6688.12
E-HCAD-30	no	4718.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

514 targeting CADM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635

Literature-anchored findings (GeneRIF, showing 26)

• Its expression is regulated in part by promoter methylation and implicates CADM-2 as a previously unrecognized tumor suppressor gene in a proportion of human prostate cancers. (PMID:21062931)
• The results indicated that CADM2 is one of the pathogenic factors for psoriasis. (PMID:21864505)
• Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma. (PMID:23643812)
• Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence (PMID:24240726)
• In the absence of SynCAMs, selective axon-axon interactions are perturbed resulting in aberrant pathfinding of sensory axons. (PMID:25335893)
• A significant association was observed for the single-nucleotide polymorphism (SNP) rs17518584 and in the joint discovery and replication meta-analysis in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. (PMID:25869804)
• CADM2 SNPs were associated with lifetime cannabis use, but the association did not reach genome-wide significance. [Meta-Analysis] (PMID:27023175)
• The study findings provide independent support for the association of CADM2 SNP rs17518584 with processing speed (and demonstrate association with additional cognitive phenotypes), among cognitively normal elderly individuals with type 2 diabetes. (PMID:28797215)
• results indicated that CADM2 is a direct target of miR-10b in HCC cells and miR-10b/CADM2 modulates EMT process and migration ability via focal adhesion kinase (FAK) /AKT signaling pathway in HCC. (PMID:29506532)
• Study provide further support for a role of cell adhesion molecule 2 in aspects of cognitive function, in particular reading and information processing speed, and suggest that this role extends to younger individuals. (PMID:30125698)
• Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial-mesenchymal transition process. (PMID:30184528)
• Results indicated that miR182 expression was increased in retinoblastoma (RB) tissues. When the expression of miR182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. (PMID:30320366)
• Study identified an association between single nucleotide polymorphisms in CADM2 and Sensation Seeking and Drug Experimentation via single variant, gene- and transcriptome-based analyses; CADM2 has been previously implicated in numerous traits related to risk taking. In addition, we identified an association between variants in CACNA1I and Negative Urgency via single-variant and gene-based analyses. (PMID:30718321)
• Study demonstrated that CADM2 was markedly downregulated in human glioma tissues compared with normal brain tissue and glioma cell lines, and the CADM2 expression level was significantly decreased in highgrade glioma tissues. Overexpression of CADM2 inhibited the proliferation of glioma cell proliferation in vitro and in vivo. (PMID:30816549)
• Genetic variation in CADM2 as a link between psychological traits and obesity. (PMID:31089183)
• ADAMTS9-AS2 and CADM2 expression and association with the prognosis in esophageal squamous cell carcinoma. (PMID:32892630)
• Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study. (PMID:33604983)
• CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis. (PMID:33910952)
• Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. (PMID:34741163)
• Long Non-Coding RNA HCG11 Inhibits Glioma Cells Proliferation and Migration through Decoying miR-590-3p and Up-Regulating CADM2. (PMID:35279660)
• Interaction of the Hemagglutinin Stalk Region with Cell Adhesion Molecule (CADM) 1 and CADM2 Mediates the Spread between Neurons and Neuropathogenicity of Measles Virus with a Hyperfusogenic Fusion Protein. (PMID:37166307)
• CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice. (PMID:37173343)
• Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma. (PMID:37228062)
• Genetic correlation for alcohol consumption between Europeans and East Asians. (PMID:37904118)
• hsa_circ_0002980 prevents proliferation, migration, invasion, and epithelial-mesenchymal transition of liver cancer cells through microRNA-1303/cell adhesion molecule 2 axis. (PMID:38126999)
• CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition. (PMID:38767769)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cadm2a	ENSDARG00000009930
danio_rerio	cadm2b	ENSDARG00000062633
mus_musculus	Cadm2	ENSMUSG00000064115
rattus_norvegicus	Cadm2	ENSRNOG00000074750
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): PVR (ENSG00000073008), CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), NECTIN4 (ENSG00000143217), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), NECTIN3 (ENSG00000177707), TIGIT (ENSG00000181847), CADM1 (ENSG00000182985), NCR3 (ENSG00000204475)

Protein

Protein identifiers

Cell adhesion molecule 2 — Q8N3J6 (reviewed: Q8N3J6)

Alternative names: Immunoglobulin superfamily member 4D, Nectin-like protein 3, Synaptic cell adhesion molecule 2

All UniProt accessions (2): Q8N3J6, G3XHN4

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation. Important for synapse organization, providing regulated trans-synaptic adhesion. Preferentially binds to oligodendrocytes. (Microbial infection) Induces cell fusion in neuron infected by a neuropathogenic strain of measles. Interacts with measles hemagglutinin to trigger hyperfusogenic F-mediated membrane fusion and presumably transsynaptic cell-to-cell transmission of the virus.

Subcellular location. Cell membrane. Synapse. Cell projection. Axon.

Similarity. Belongs to the nectin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N3J6-1	1	yes
Q8N3J6-2	2
Q8N3J6-3	3
Q8N3J6-4	5, 7
Q8N3J6-5	6, 8

RefSeq proteins (14): NP_001161146, NP_001161147, NP_001243431, NP_001243432, NP_001243433, NP_001243434, NP_001362889, NP_001362890, NP_001362893, NP_001362896, NP_001362897, NP_001368892, NP_001368893, NP_694854 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003585	Neurexin-like	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686, PF08205, PF13927

UniProt features (22 total): splice variant 5, glycosylation site 3, disulfide bond 3, domain 3, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3J6-F1	82.53	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 423

Disulfide bonds (3): 44–104, 146–203, 248–296

Glycosylation sites (3): 51, 291, 31

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-1500931	Cell-Cell communication
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization

MSigDB gene sets: 352 (showing top): RNGTGGGC_UNKNOWN, HNF3ALPHA_Q6, GCANCTGNY_MYOD_Q6, SP3_Q3, TATTATA_MIR374, AREB6_01, TAL1ALPHAE47_01, FOXO4_01, CTATGCA_MIR153, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SP1_Q2_01, ATGTTAA_MIR302C, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_CELL_ADHESION

GO Biological Process (2): homophilic cell-cell adhesion (GO:0007156), cell adhesion (GO:0007155)

GO Molecular Function (0):

GO Cellular Component (6): plasma membrane (GO:0005886), axon (GO:0030424), neuronal cell body membrane (GO:0032809), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-cell adhesion	1
cellular process	1
membrane	1
cell periphery	1
neuron projection	1
neuronal cell body	1
cell body membrane	1
cell junction	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CADM2	EPB41	P11171	700
CADM2	CADM1	Q9BY67	653
CADM2	TMEM160	Q9NX00	542
CADM2	DNAJC27	Q9NZQ0	540
CADM2	NUDT3	O95989	528
CADM2	GNPDA2	Q8TDQ7	507
CADM2	ZNF608	Q9ULD9	507
CADM2	TMEM18	Q96B42	507
CADM2	QPCTL	Q9NXS2	506
CADM2	NRXN3	Q9Y4C0	506
CADM2	KCNS1	Q96KK3	490
CADM2	SEC16B	Q96JE7	479
CADM2	LINGO2	Q7L985	477
CADM2	V9GXZ4	V9GXZ4	475
CADM2	POC5	Q8NA72	473

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CADM2	MYO1B	psi-mi:“MI:0915”(physical association)	0.400
CADM1	CADM2	psi-mi:“MI:0915”(physical association)	0.400
CADM2	CADM1	psi-mi:“MI:0915”(physical association)	0.400
CADM2	CADM4	psi-mi:“MI:0915”(physical association)	0.400
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270

BioGRID (8): CADM2 (Affinity Capture-MS), CADM2 (Proximity Label-MS), CADM2 (Affinity Capture-MS), CADM2 (Affinity Capture-RNA), CADM2 (Proximity Label-MS), CADM2 (Affinity Capture-MS), CADM2 (Affinity Capture-MS), CCDC15 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, B0JYH6, F1LW30, O35112, O46634, O46651, P0C673, P17948, P26453, P35969, P42292, P53767, Q08DK1, Q13740, Q15198, Q1WIM2, Q2PFX1, Q504C1, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5RJP7, Q5U2P2, Q5VJ70, Q61490, Q6DJ83, Q6PE55, Q6UXZ4, Q6X936, Q7T2Z5, Q7TSN7, Q80W68, Q8BLQ9, Q8BR86, Q8IZU9, Q8K1S2, Q8N3J6, Q8QHL3

Diamond homologs: A6NGN9, B3MKS0, B3N666, B4GBH0, B4GKZ8, B4HY03, B4JEF2, B4KJW1, B4LRN7, B4MR28, B4N072, B4NZY8, B4Q599, P0C5E3, Q05793, Q1WIM2, Q24372, Q29JX6, Q5DTJ9, Q5R412, Q7Z3B1, Q80Z24, Q86TC9, Q8BFR2, Q8BLI0, Q8BLQ9, Q8HW98, Q8N3J6, Q8WX93, Q9ET54, Q9I7U4, Q9P121, Q9VM64, Q9W6V2, Q9Z0J8, O95727, Q13449, Q149L7, Q1WIM1, Q1WIM3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
mir-10b	“down-regulates quantity”	CADM2	destabilization
CADM2	“up-regulates activity”	PTK2
CADM2	up-regulates	Cell_adhesion

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — MEL.

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	54
Likely benign	4
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57801	GRCh38/hg38 3p12.2-12.1(chr3:81504313-85127899)x1	Pathogenic

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
3:85802042:TTTA:T	acceptor_loss	1.0000
3:85802043:TTA:T	acceptor_loss	1.0000
3:85802045:A:AG	acceptor_gain	1.0000
3:85802045:A:AT	acceptor_loss	1.0000
3:85802046:G:GG	acceptor_gain	1.0000
3:85802046:GGCA:G	acceptor_gain	1.0000
3:85802192:GAAAG:G	donor_gain	1.0000
3:85802193:AAAG:A	donor_loss	1.0000
3:85802194:AAGG:A	donor_loss	1.0000
3:85802195:AGG:A	donor_loss	1.0000
3:85802196:GGTGA:G	donor_loss	1.0000
3:85802197:GTGA:G	donor_loss	1.0000
3:85802198:T:G	donor_loss	1.0000
3:85726545:AAAGG:A	donor_loss	0.9900
3:85726546:AAGG:A	donor_loss	0.9900
3:85726550:T:G	donor_loss	0.9900
3:85802045:AG:A	acceptor_gain	0.9900
3:85802046:GG:G	acceptor_gain	0.9900
3:85802046:GGC:G	acceptor_gain	0.9900
3:85808641:GCTT:G	donor_gain	0.9900
3:85812667:T:G	donor_gain	0.9900
3:85812667:T:TG	donor_gain	0.9900
3:85840410:ACAT:A	donor_gain	0.9900
3:85742890:G:T	donor_gain	0.9800
3:85793798:GTT:G	acceptor_gain	0.9800
3:85802197:G:GG	donor_gain	0.9800
3:85808640:AGCTT:A	donor_gain	0.9700
3:85808641:GCTTG:G	donor_gain	0.9700
3:85726549:G:GG	donor_gain	0.9600
3:85781468:A:T	donor_gain	0.9600

AlphaMissense

2644 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:85802115:T:C	C44R	1.000
3:85802116:G:A	C44Y	1.000
3:85802117:C:G	C44W	1.000
3:85802151:T:A	W56R	1.000
3:85802151:T:C	W56R	1.000
3:85802152:G:C	W56S	1.000
3:85802153:G:C	W56C	1.000
3:85802153:G:T	W56C	1.000
3:85883306:G:T	R76M	1.000
3:85883372:A:T	D98V	1.000
3:85883383:T:G	Y102D	1.000
3:85883384:A:C	Y102S	1.000
3:85883384:A:G	Y102C	1.000
3:85883389:T:A	C104S	1.000
3:85883389:T:C	C104R	1.000
3:85883390:G:A	C104Y	1.000
3:85883390:G:C	C104S	1.000
3:85883391:T:G	C104W	1.000
3:85883392:T:C	S105P	1.000
3:85883432:T:C	L118P	1.000
3:85883438:T:A	V120D	1.000
3:85886300:T:A	W159R	1.000
3:85886300:T:C	W159R	1.000
3:85886302:G:C	W159C	1.000
3:85886302:G:T	W159C	1.000
3:85935835:T:C	C248R	1.000
3:85961485:T:A	W261R	1.000
3:85961485:T:C	W261R	1.000
3:85961486:G:C	W261S	1.000
3:85961487:G:C	W261C	1.000

dbSNP variants (sampled 300 via entrez): RS1000000101 (3:85651351 C>G,T), RS1000002058 (3:85648597 CT>C), RS1000003121 (3:85459987 T>C), RS1000007330 (3:85086930 A>G,T), RS1000009314 (3:85740123 T>A,C), RS1000014195 (3:85693225 G>A,C), RS1000016817 (3:85411621 T>C), RS1000018933 (3:85287798 C>A), RS1000026000 (3:85338455 C>T), RS1000028624 (3:85533678 A>G), RS1000035487 (3:85125370 T>G), RS1000039349 (3:85449913 G>C), RS1000039545 (3:85912928 T>C), RS1000041534 (3:85963861 T>C), RS1000043602 (3:85489391 A>T)

Disease associations

OMIM: gene MIM:609938 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

195 associations (top):

Study	Trait	p-value
GCST000830_19	Body mass index	4.000000e-11
GCST001521_19	Subcutaneous adipose tissue	2.000000e-06
GCST001521_26	Subcutaneous adipose tissue	4.000000e-06
GCST001525_38	Visceral fat	3.000000e-06
GCST001531_10	Temperament	5.000000e-06
GCST001953_58	Obesity	3.000000e-11
GCST002599_2	Longevity (90 years and older)	9.000000e-07
GCST002774_11	Cognitive function	1.000000e-06
GCST002783_24	Body mass index	1.000000e-11
GCST002783_374	Body mass index	1.000000e-14
GCST002783_507	Body mass index	2.000000e-14
GCST002783_99	Body mass index	4.000000e-07
GCST002813_2	Alzheimer’s disease in APOE e4+ carriers	9.000000e-06
GCST002831_5	Lead levels in blood	1.000000e-06
GCST002850_2	Information processing speed	3.000000e-09
GCST002932_24	Manganese levels	1.000000e-06
GCST003262_553	Post bronchodilator FEV1	4.000000e-06
GCST003262_554	Post bronchodilator FEV1	3.000000e-06
GCST003262_555	Post bronchodilator FEV1	4.000000e-06
GCST003262_556	Post bronchodilator FEV1	4.000000e-06
GCST003262_557	Post bronchodilator FEV1	4.000000e-06
GCST003262_833	Post bronchodilator FEV1	3.000000e-06
GCST003262_879	Post bronchodilator FEV1	1.000000e-06
GCST003262_880	Post bronchodilator FEV1	1.000000e-06
GCST003262_881	Post bronchodilator FEV1	1.000000e-06
GCST003262_882	Post bronchodilator FEV1	3.000000e-06
GCST003264_35	Post bronchodilator FEV1/FVC ratio	9.000000e-07
GCST003264_36	Post bronchodilator FEV1/FVC ratio	9.000000e-07
GCST003264_37	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_38	Post bronchodilator FEV1/FVC ratio	2.000000e-06

EFO canonical traits (45, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004825	temperament and character inventory
EFO:0004337	intelligence
EFO:0004363	information processing speed
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004784	self reported educational attainment
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004703	age at menarche
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008579	risk-taking behaviour
EFO:0004695	intraocular pressure measurement
EFO:0007585	Cannabis use
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0009592	social interaction measurement
EFO:0009594	irritability measurement
EFO:0009588	feeling “fed-up” measurement
EFO:0009597	feeling nervous measurement
EFO:0009589	worry measurement
EFO:0009596	feeling tense measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0005301	reading and spelling ability
EFO:0008328	chronotype measurement
EFO:0005670	smoking initiation
EFO:0006946	behavioural disinhibition measurement
EFO:0007010	drug use measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs62250713	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs62250713	CADM2	3	1.50	1	ethanol

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Aflatoxin B1	affects expression, decreases methylation, increases methylation	3
methylmercuric chloride	increases expression, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Thimerosal	increases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

75 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists