JAM3
protein-codingjunctional adhesion molecule 3, the group of V-set domain containing|Ig-like cell adhesion molecule family|Small nucleolar RNA protein coding host genes
Gene summary
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, the this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions. The encoded protein is a member of the junctional adhesion molecule protein family and acts as a receptor for another member of this family. A mutation in an intron of this gene is associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013394
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013394
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013394
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013394
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Neurologic; Ophthalmologic; Renal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to JAM3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032801.5. 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 | 33 | 1 | 35 | ||
| missense | 2 | 1 | 86 | 6 | 1 | 96 |
| nonsense | 1 | 1 | 1 | 3 | ||
| start loss | 2 | 1 | 3 | |||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 2 | 4 | |||
| Total | 11 | 4 | 90 | 39 | 2 | 146 |
Highest pathogenic variant AF is 0.0000068297445
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116190.3 | 9 | MANE Select | |
| Ensembl | ENSP00000299106.4 | 9 | MANE Select | |
| RefSeq | NP_001192258.1 | 8 | Standard | |
| Ensembl | ENSP00000395742.3 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| jam3b | Danio rerio | Structure: fast muscle cell Quality: mononucleate abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Tight junction - Homo sapiens (human)
- Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
- Leukocyte transendothelial migration - Homo sapiens (human)
- Integrin cell surface interactions
Biological Process
- angiogenesis
- neutrophil homeostasis
- adaptive immune response
- myeloid progenitor cell differentiation
- leukocyte migration involved in inflammatory response
Molecular Function
- integrin binding
- protein binding
- protein homodimerization activity
- protein heterodimerization activity
Cellular Component
- extracellular space
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299106
- Coding exons
- 9
- Length
- 83077
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.867 | 205 | 173 | 1.19 | 0.0000108 | 2013 |
| Missense (PolyPhen) | 54 | 63.581 | 0.84931 | 747 | ||
| Synonymous | -1.54 | 84 | 67.8 | 1.24 | 0.00000434 | 618 |
| Loss of Function | 2.04 | 8 | 17.1 | 0.467 | 8.62e-7 | 200 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates cell-cell adhesion (PubMed:11590146, PubMed:12208882, PubMed:15194813). Functions as counter-receptor for JAM2 (PubMed:11590146). Functions as a counter-receptor for ITGAM, mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN) (PubMed:12208882, PubMed:15194813). Plays a role in angiogenesis (PubMed:23255084). May play a role in the regulation of cell migration (Probable). Required for normal polarization and acrosome formation in developing spermatids, and for normal male fertility (By similarity). {ECO:0000250|UniProtKB:Q9D8B7, ECO:0000269|PubMed:11590146, ECO:0000269|PubMed:12208882, ECO:0000269|PubMed:15194813, ECO:0000269|PubMed:23255084, ECO:0000305|PubMed:28196865}.;
- Disease
- DISEASE: Hemorrhagic destruction of the brain with subependymal calcification and cataracts (HDBSCC) [MIM:613730]: A syndrome characterized by congenital cataracts and severe brain abnormalities apparently resulting from hemorrhagic destruction of the brain parenchyma, including the cerebral white matter and basal ganglia. Patients manifest profound developmental delay, and other neurologic features included seizures, spasticity, and hyperreflexia. The clinical course is very severe resulting in death in infancy. Brain imaging shows multifocal intraparenchymal hemorrhage with associated liquefaction and massive cystic degeneration, and calcification in the subependymal region and in brain tissue. {ECO:0000269|PubMed:21109224, ECO:0000269|PubMed:23255084}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.691
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.637
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |