JAM2

Summary

JAM2 (junctional adhesion molecule 2, HGNC:14686) is a protein-coding gene on chromosome 21q21.3, encoding Junctional adhesion molecule B (P57087). Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes.

This gene belongs to the immunoglobulin superfamily, and the junctional adhesion molecule (JAM) family. The protein encoded by this gene is a type I membrane protein that is localized at the tight junctions of both epithelial and endothelial cells. It acts as an adhesive ligand for interacting with a variety of immune cell types, and may play a role in lymphocyte homing to secondary lymphoid organs. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 58494 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 8, autosomal recessive (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 91 total — 9 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• MANE Select transcript: NM_021219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14686
Approved symbol	JAM2
Name	junctional adhesion molecule 2
Location	21q21.3
Locus type	gene with protein product
Status	Approved
Aliases	VE-JAM, JAM-B, JAMB, CD322, JAM-2
Ensembl gene	ENSG00000154721
Ensembl biotype	protein_coding
OMIM	606870
Entrez	58494

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000312957, ENST00000400532, ENST00000460679, ENST00000471689, ENST00000477351, ENST00000480456, ENST00000492962, ENST00000948521

RefSeq mRNA: 3 — MANE Select: NM_021219 NM_001270407, NM_001270408, NM_021219

CCDS: CCDS42911, CCDS58787, CCDS58788

Canonical transcript exons

ENST00000480456 — 10 exons

Exon	Start	End
ENSE00001017300	25693756	25693908
ENSE00001017301	25689866	25689973
ENSE00001017302	25698677	25698879
ENSE00001017305	25702170	25702269
ENSE00001017308	25683883	25683948
ENSE00001764187	25709434	25709449
ENSE00001862906	25714640	25717562
ENSE00003467564	25712340	25712382
ENSE00003679527	25705979	25706086
ENSE00003843052	25639258	25639888

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9214 / max 236.2783, expressed in 1069 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188666	4.0956	783
188662	2.8000	694
188661	2.7432	613
188657	1.1168	375
188658	0.9128	311
188664	0.8090	351
188660	0.7114	311
188665	0.4730	251
188667	0.3115	181
188659	0.2725	170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.13	gold quality
tendon of biceps brachii	UBERON:0008188	96.69	gold quality
vena cava	UBERON:0004087	95.45	gold quality
medial globus pallidus	UBERON:0002477	94.90	gold quality
ganglionic eminence	UBERON:0004023	94.78	gold quality
pericardium	UBERON:0002407	93.82	gold quality
mucosa of stomach	UBERON:0001199	93.76	gold quality
globus pallidus	UBERON:0001875	93.36	gold quality
body of uterus	UBERON:0009853	93.17	gold quality
colonic epithelium	UBERON:0000397	93.06	gold quality
tibial nerve	UBERON:0001323	93.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.91	gold quality
endocervix	UBERON:0000458	92.79	gold quality
trigeminal ganglion	UBERON:0001675	92.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.49	gold quality
lower esophagus	UBERON:0013473	92.43	gold quality
myometrium	UBERON:0001296	92.39	gold quality
placenta	UBERON:0001987	91.99	gold quality
smooth muscle tissue	UBERON:0001135	91.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.61	gold quality
gall bladder	UBERON:0002110	91.60	gold quality
apex of heart	UBERON:0002098	91.26	gold quality
omental fat pad	UBERON:0010414	91.23	gold quality
peritoneum	UBERON:0002358	91.20	gold quality
right testis	UBERON:0004534	91.18	gold quality
decidua	UBERON:0002450	91.11	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.00	gold quality
tendon	UBERON:0000043	90.99	gold quality
left uterine tube	UBERON:0001303	90.96	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1244.40
E-HCAD-11	yes	48.19
E-HCAD-1	yes	40.76
E-GEOD-135922	yes	40.67
E-CURD-46	yes	29.87
E-MTAB-6701	yes	28.65
E-MTAB-8410	yes	21.77
E-GEOD-93593	yes	16.27
E-MTAB-6678	yes	13.40
E-MTAB-6379	no	4.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

128 targeting JAM2, 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-4455	100.00	65.48	1587
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3140-3P	99.88	68.47	2069

Literature-anchored findings (GeneRIF, showing 17)

• Cloning and discovery as adhesion receptor for T cells (PMID:10945976)
• role as an adhesive ligand for interacting with a variety of immune cell types (PMID:11823489)
• Discovery as ligand for the integrin alpha4beta1 (PMID:12070135)
• interacts with alpha4beta1; Facilitation by JAM3 (PMID:12070135)
• Results suggest a role for junctional adhesion molecule-2 (JAM-2) in facilitating transmigration in endothelial cells (PMID:12476045)
• Examine JAM-2 expression in normal/inflammed lymphatic endothelium. (PMID:17822725)
• These data brought new evidences for the role of JAM2 and JAM3 in progression of gastric adenocarcinoma (PMID:23277282)
• Function of Jam-B/Jam-C interaction in homing and mobilization of human and mouse hematopoietic stem and progenitor cells. (PMID:24357068)
• This study showed thatJAM2 (rs2829841; intronic), associated with Alzheimer disease. (PMID:25649652)
• JAM-2 may function as a putative tumour suppressor in the progression and metastasis of colorectal cancer (PMID:26782073)
• this review briefly focuses on what is currently known about the structure, function, and mechanism of JAM-B, with particular emphasis on cancer. [review] (PMID:27121546)
• iR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2 (PMID:29575013)
• mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit (PMID:31851307)
• Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification (PMID:32142645)
• JAM2 predicts a good prognosis and inhibits invasion and migration by suppressing EMT pathway in breast cancer. (PMID:34923424)
• JAM2 is a prognostic biomarker and inhibits proliferation, metastasis and epithelial-mesenchymal transition in lung adenocarcinoma. (PMID:38404047)
• JAM2 variants can be more common in primary familial brain calcification (PFBC) cases than those appear; may be due to a founder mutation. (PMID:38441788)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	jam2a	ENSDARG00000058996
danio_rerio	jam2b	ENSDARG00000079071
mus_musculus	Jam2	ENSMUSG00000053062
rattus_norvegicus	Jam2	ENSRNOG00000042848

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), VSIR (ENSG00000107738), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

Junctional adhesion molecule B — P57087 (reviewed: P57087)

Alternative names: Junctional adhesion molecule 2, Vascular endothelial junction-associated molecule

All UniProt accessions (2): P57087, H0YEX9

UniProt curated annotations — full annotation on UniProt →

Function. Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes. Plays a role in homing and mobilization of hematopoietic stem and progenitor cells within the bone marrow. At the surface of bone marrow stromal cells, it contributes to the retention of the hematopoietic stem and progenitor cells expressing JAM3. Plays a central role in leukocytes extravasation by facilitating not only transmigration but also tethering and rolling of leukocytes along the endothelium. Tethering and rolling of leukocytes are dependent on the binding by JAM2 of the integrin alpha-4/beta-1. Plays a role in spermatogenesis where JAM2 and JAM3, which are respectively expressed by Sertoli and germ cells, mediate an interaction between both cell types and play an essential role in the anchorage of germ cells onto Sertoli cells and the assembly of cell polarity complexes during spermatid differentiation. Also functions as an inhibitory somatodendritic cue that prevents the myelination of non-axonal parts of neurons. During myogenesis, it is involved in myocyte fusion. May also play a role in angiogenesis.

Subcellular location. Cell membrane. Cell junction. Tight junction.

Tissue specificity. Highly expressed in heart, placenta, lung, foreskin and lymph node. Prominently expressed on high endothelial venules and also present on the endothelia of other vessels (at protein level). Also expressed in the brain in the caudate nuclei.

Disease relevance. Basal ganglia calcification, idiopathic, 8, autosomal recessive (IBGC8) [MIM:618824] A form of basal ganglia calcification, a genetically heterogeneous condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The Ig-like V-type domain is necessary and sufficient to mediate interaction with JAM3 and integrin alpha-4/beta-1.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P57087-1	1	yes
P57087-2	2
P57087-3	3

RefSeq proteins (3): NP_001257336, NP_001257337, NP_067042* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042625	JAM2	Family

Pfam: PF07686, PF13927

UniProt features (21 total): sequence variant 5, glycosylation site 3, disulfide bond 2, splice variant 2, topological domain 2, domain 2, signal peptide 1, chain 1, mutagenesis site 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57087-F1	82.91	0.62

Functional residue map

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

Disulfide bonds (2): 50–109, 155–214

Glycosylation sites (3): 98, 187, 236

Mutagenesis-validated functional residues (1):

Position	Phenotype
82	no effect on binding of jam3 or integrin.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-109582	Hemostasis
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 280 (showing top): MODULE_64, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, KEGG_TIGHT_JUNCTION, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_CELL_CELL_ADHESION, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_CELLULAR_EXTRAVASATION

GO Biological Process (11): leukocyte cell-cell adhesion (GO:0007159), spermatid development (GO:0007286), negative regulation of myelination (GO:0031642), maintenance of blood-brain barrier (GO:0035633), cellular extravasation (GO:0045123), leukocyte tethering or rolling (GO:0050901), lymphocyte aggregation (GO:0071593), hematopoietic stem cell migration to bone marrow (GO:0097241), cell-cell adhesion (GO:0098609), positive regulation of lymphocyte migration (GO:2000403), leukocyte migration (GO:0050900)

GO Molecular Function (2): integrin binding (GO:0005178), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell surface (GO:0009986), somatodendritic compartment (GO:0036477), cell-cell contact zone (GO:0044291), tight junction (GO:0070160), protein complex involved in cell adhesion (GO:0098636), cell-cell junction (GO:0005911), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-cell junction	2
cell-cell adhesion	1
germ cell development	1
spermatid differentiation	1
regulation of myelination	1
negative regulation of nervous system process	1
myelination	1
negative regulation of cellular process	1
tissue homeostasis	1
leukocyte migration	1
cellular extravasation	1
leukocyte adhesion to vascular endothelial cell	1
leukocyte aggregation	1
hematopoietic stem cell migration	1
cell adhesion	1
positive regulation of mononuclear cell migration	1
lymphocyte migration	1
regulation of lymphocyte migration	1
immune system process	1
cell migration	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
protein-containing complex	1
anchoring junction	1
cell junction	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JAM2	TJP1	Q07157	913
JAM2	ITGB2	P05107	874
JAM2	JAM3	Q9BX67	854
JAM2	OCLN	Q16625	734
JAM2	CLDN1	O95832	702
JAM2	ITGA4	P13612	699
JAM2	IGSF5	Q9NSI5	698
JAM2	F11R	Q9Y624	697
JAM2	PTTG1IP	P53801	691
JAM2	CLDN7	O95471	670
JAM2	PKNOX1	P55347	589
JAM2	JAML	Q86YT9	588
JAM2	NECTIN1	Q15223	581
JAM2	TJP2	Q9UDY2	568
JAM2	PARD6B	Q9BYG5	564

IntAct

132 interactions, top by confidence:

A	B	Type	Score
JAM2	JAM3	psi-mi:“MI:0915”(physical association)	0.710
JAM3	JAM2	psi-mi:“MI:0915”(physical association)	0.710
JAM3	JAM2	psi-mi:“MI:0407”(direct interaction)	0.710
PARD3	JAM2	psi-mi:“MI:0407”(direct interaction)	0.610
JAM2	PARD3	psi-mi:“MI:0915”(physical association)	0.610
JAM2	PICK1	psi-mi:“MI:0407”(direct interaction)	0.590
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
JAM2	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
PATJ	JAM2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA3	JAM2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	JAM2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	JAM2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG4	JAM2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (15): JAM2 (Reconstituted Complex), PARD3 (Affinity Capture-Western), JAM2 (Reconstituted Complex), JAM2 (Affinity Capture-RNA), JAM2 (Affinity Capture-MS), PICK1 (Two-hybrid), JAM3 (Reconstituted Complex), JAM2 (Reconstituted Complex), JAM2 (Reconstituted Complex), TDP2 (Two-hybrid), NME3 (Two-hybrid), YBX1 (Two-hybrid), SOX8 (Two-hybrid), JAM2 (Two-hybrid), JAM2 (Two-hybrid)

ESM2 similar proteins: A0A8M2B818, A3KPA0, A5D7C3, B0JYH6, O35112, O46634, O46651, O88792, P17790, P18461, P18572, P21802, P21803, P26453, P35613, P42292, P57087, P78310, P97792, Q01638, Q13740, Q15198, Q1WIM2, Q2PFX1, Q2WGK2, Q3V3F6, Q5R764, Q5RJP7, Q61490, Q66KX2, Q68FQ2, Q6DJ83, Q6PE55, Q6UWV2, Q7ZXX1, Q8BLQ9, Q8N3J6, Q8WMV3, Q90Y50, Q99795

Diamond homologs: A0A0R4IGV4, P57087, P98160, Q05793, Q1WIM1, Q2WGK2, Q8NFZ8, Q8R464, Q925F2, Q9JI59, Q9XT56, Q9Y624, A3KPA0, F1NY98, O15146, O60469, P29534, Q24372, Q26474, Q61006, Q62838, Q68FQ2, Q8N475, Q8VHZ8, Q967D7, Q9BX67, Q9D8B7, Q9ERC8, A0JM20, A0N0X6, A1KZ92, A2ABU4, A2CG49, A3KN33, A4IGL7, B4F785, D2HFT7, D3YXG0, D3ZEY0, E9Q8Q6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Long-term potentiation	5	45.8×	2e-06
Assembly and cell surface presentation of NMDA receptors	9	43.9×	3e-11
Neurexins and neuroligins	10	37.9×	1e-11
Protein-protein interactions at synapses	6	30.6×	1e-06
RHOB GTPase cycle	5	14.8×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	82.0×	2e-16
protein localization to synapse	6	58.9×	6e-08
receptor clustering	7	56.0×	7e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
cell-cell adhesion	11	14.3×	3e-08
protein-containing complex assembly	9	13.1×	2e-06
regulation of small GTPase mediated signal transduction	5	9.2×	4e-03
chemical synaptic transmission	7	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	1
Uncertain significance	38
Likely benign	2
Benign	23

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
18104	NC_000021.9:g.(25431701_?)_(?_26466216)dup	Pathogenic
829531	NM_021219.4(JAM2):c.143del (p.Ile47_Leu48insTer)	Pathogenic
829533	NM_021219.4(JAM2):c.1A>G (p.Met1Val)	Pathogenic
829535	NM_021219.4(JAM2):c.504G>C (p.Trp168Cys)	Pathogenic
829537	NM_021219.4:c.(67+1_68-1)_(394+1_395-1)del	Pathogenic
829539	NM_021219.4(JAM2):c.323G>A (p.Arg108His)	Pathogenic
829541	NM_021219.4(JAM2):c.685C>T (p.Arg229Ter)	Pathogenic
829543	NM_021219.4(JAM2):c.395-1dup	Pathogenic
829545	NM_021219.4(JAM2):c.177_180del (p.Ser59_Arg60insTer)	Pathogenic
4823620	NM_021219.4(JAM2):c.805+2T>A	Likely pathogenic

SpliceAI

2071 predictions. Top by Δscore:

Variant	Effect	Δscore
21:25639884:GGGCT:G	donor_gain	1.0000
21:25639885:GGCT:G	donor_gain	1.0000
21:25639885:GGCTG:G	donor_gain	1.0000
21:25639886:GCT:G	donor_gain	1.0000
21:25639886:GCTG:G	donor_gain	1.0000
21:25639889:G:GG	donor_gain	1.0000
21:25693878:G:GT	donor_gain	1.0000
21:25693899:G:GT	donor_gain	1.0000
21:25693899:G:T	donor_gain	1.0000
21:25702164:A:AG	acceptor_gain	1.0000
21:25702165:A:G	acceptor_gain	1.0000
21:25702192:T:A	acceptor_gain	1.0000
21:25706087:G:GG	donor_gain	1.0000
21:25711477:GACA:G	donor_gain	1.0000
21:25711481:G:GG	donor_gain	1.0000
21:25711564:GTCTC:G	donor_gain	1.0000
21:25711569:G:GG	donor_gain	1.0000
21:25712334:A:AG	acceptor_gain	1.0000
21:25712381:ATGTG:A	donor_loss	1.0000
21:25712383:G:GG	donor_gain	1.0000
21:25712385:G:GT	donor_loss	1.0000
21:25712386:AG:A	donor_loss	1.0000
21:25639874:T:TA	donor_gain	0.9900
21:25639875:G:GA	donor_gain	0.9900
21:25639887:CT:C	donor_gain	0.9900
21:25639888:TGTA:T	donor_loss	0.9900
21:25639889:G:GC	donor_loss	0.9900
21:25639890:TAA:T	donor_loss	0.9900
21:25639891:AAGTT:A	donor_loss	0.9900
21:25683877:TTTCA:T	acceptor_loss	0.9900

AlphaMissense

1928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:25689919:T:A	W63R	0.998
21:25689919:T:C	W63R	0.998
21:25689921:G:C	W63C	0.998
21:25689921:G:T	W63C	0.998
21:25693833:T:G	Y107D	0.998
21:25698784:T:A	W168R	0.998
21:25698784:T:C	W168R	0.998
21:25698786:G:C	W168C	0.998
21:25698786:G:T	W168C	0.998
21:25693834:A:C	Y107S	0.997
21:25693834:A:G	Y107C	0.997
21:25693839:T:A	C109S	0.997
21:25693840:G:C	C109S	0.997
21:25698745:T:A	C155S	0.997
21:25698745:T:C	C155R	0.997
21:25698746:G:C	C155S	0.997
21:25698878:T:C	L199P	0.997
21:25702206:T:G	Y212D	0.997
21:25702207:A:G	Y212C	0.997
21:25702212:T:A	C214S	0.997
21:25702213:G:C	C214S	0.997
21:25698740:T:C	L153P	0.996
21:25702207:A:C	Y212S	0.996
21:25702212:T:C	C214R	0.996
21:25702213:G:A	C214Y	0.996
21:25702226:T:A	N218K	0.996
21:25702226:T:G	N218K	0.996
21:25689920:G:C	W63S	0.995
21:25693839:T:C	C109R	0.995
21:25693837:G:C	R108P	0.994

dbSNP variants (sampled 300 via entrez): RS1000008823 (21:25696593 A>C), RS1000048472 (21:25658161 G>A), RS1000057032 (21:25677516 A>T), RS1000059518 (21:25696360 C>A,T), RS1000101846 (21:25658504 T>C), RS1000186547 (21:25682479 T>A,G), RS1000240490 (21:25682688 C>G), RS1000287152 (21:25688947 T>C), RS1000293882 (21:25676026 G>A,T), RS1000330126 (21:25651757 G>A), RS1000369897 (21:25644774 G>A), RS1000397226 (21:25665304 T>C), RS1000430528 (21:25682324 G>C,T), RS1000459460 (21:25670632 G>T), RS1000465530 (21:25639812 C>T)

Disease associations

OMIM: gene MIM:606870 | disease phenotypes: MIM:618824

GenCC curated gene-disease

Disease	Classification	Inheritance
basal ganglia calcification, idiopathic, 8, autosomal recessive	Strong	Autosomal recessive
bilateral striopallidodentate calcinosis	Supportive	Autosomal dominant

Mondo (2): basal ganglia calcification, idiopathic, 8, autosomal recessive (MONDO:0032938), bilateral striopallidodentate calcinosis (MONDO:0008947)

Orphanet (0):

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000298	Mask-like facies
HP:0000338	Hypomimic face
HP:0000639	Nystagmus
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000726	Dementia
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000802	Impotence
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001350	Slurred speech
HP:0002015	Dysphagia
HP:0002063	Rigidity

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000477_51	Cognitive performance	2.000000e-06
GCST003082_7	Longitudinal change in brain amyloid plaque burden	3.000000e-06
GCST005351_14	Carboplatin disposition in epthelial ovarian cancer	9.000000e-06
GCST009391_1164	Metabolite levels	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0007646	amyloid plaque accumulation rate
EFO:0010460	anthranilic acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536275	Fahr’s disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5483010 (PROTEIN COMPLEX)

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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Estradiol	increases expression, affects expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
vanadyl sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NSC668394	decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression	1
Cannabidiol	decreases expression	1
Cytarabine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5383469	Binding	Inhibition of N-terminal GST-tagged GRASP55 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/JAM-B (unknown origin) complex incubated for 16 hrs by HTRF assay	Discovery of a PDZ Domain Inhibitor Targeting the Syndecan/Syntenin Protein-Protein Interaction: A Semi-Automated “Hit Identification-to-Optimization” Approach. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8GX	Ubigene hCMEC/D3 JAM2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05662111	PHASE2	RECRUITING	Treatment of Ectopic Calcification in Fahr’s Disease or Syndrome