TMIGD2
protein-codingtransmembrane and immunoglobulin domain containing 2, the group of Immunoglobulin like domain containing
Gene summary
Enables coreceptor activity. Involved in positive regulation of T cell activation; positive regulation of angiogenesis; and positive regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMIGD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001169126.2. 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 | 3 | 4 | |||
| missense | 45 | 9 | 2 | 56 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 46 | 10 | 5 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001162597.1 | 5 | MANE Select | |
| Ensembl | ENSP00000470561.1 | 5 | MANE Select | |
| RefSeq | NP_001295161.1 | 4 | Standard | |
| RefSeq | NP_001382478.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of cytokine production
- immunoglobulin production
- immune response
- T cell costimulation
- positive regulation of activated T cell proliferation
Molecular Function
- protein binding
- coreceptor activity
Cellular Component
- extracellular space
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301272
- Coding exons
- 5
- Length
- 10200
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125747
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0953 | 169 | 173 | 0.980 | 0.0000105 | 1801 |
| Missense (PolyPhen) | 25 | 35.792 | 0.69849 | 337 | ||
| Synonymous | -1.25 | 88 | 74.3 | 1.18 | 0.00000481 | 571 |
| Loss of Function | 0.291 | 8 | 8.94 | 0.895 | 3.85e-7 | 93 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in cell-cell interaction, cell migration, and angiogenesis. Through interaction with HHLA2, costimulates T- cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade. {ECO:0000269|PubMed:22419821, ECO:0000269|PubMed:23784006}.;
Intolerance Scores
- LoFtool
- 0.767
- RVIS EVS
- 1.93
- RVIS percentile EVS
- 97.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00100
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |