JAM2
protein-codingjunctional adhesion molecule 2, the group of V-set domain containing|CD molecules|Ig-like cell adhesion molecule family|I-set domain containing
Gene summary
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. [provided by RefSeq, Jul 2012]
- C21orf43
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0008947
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0032938
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032938
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032938
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Neurologic
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 JAM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021219.4. 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 | 2 | 3 | |||
| missense | 2 | 44 | 1 | 2 | 49 | |
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 7 | 1 | 47 | 2 | 4 | 61 |
Highest pathogenic variant AF is 0.000031452513
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067042.1 | 10 | MANE Select | |
| Ensembl | ENSP00000420419.1 | 10 | MANE Select | |
| RefSeq | NP_001257336.1 | 9 | Standard | |
| RefSeq | NP_001257337.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| jam2a | 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
- negative regulation of cell adhesion
- extracellular matrix organization
- leukocyte migration
- cell-cell adhesion
Molecular Function
- protein binding
- protein heterodimerization activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400532
- Coding exons
- 10
- Length
- 78291
- Individuals with no LoFs
- 124768
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 124797
- p
- 0.000116
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 127 | 166 | 0.764 | 0.00000880 | 1981 |
| Missense (PolyPhen) | 26 | 45.846 | 0.56712 | 567 | ||
| Synonymous | 1.95 | 42 | 61.4 | 0.684 | 0.00000323 | 623 |
| Loss of Function | 2.53 | 7 | 18.8 | 0.372 | 0.00000106 | 218 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00032 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000063 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00014 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in the processes of lymphocyte homing to secondary lymphoid organs.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.625
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.855
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |