TMEM88
protein-codingtransmembrane protein 88
Gene summary
Predicted to enable PDZ domain binding activity. Involved in negative regulation of canonical Wnt signaling pathway; protein localization to plasma membrane; and protein stabilization. Located in cytosol and plasma membrane. [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 ~1.0 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 TMEM88 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_203411.2. 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 | 0 | |||||
| missense | 36 | 36 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 0 | 0 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_981956.1 | 2 | MANE Select | |
| Ensembl | ENSP00000301599.6 | 2 | MANE Select | |
| RefSeq | NP_001306870.1 | 2 | Standard | |
| Ensembl | ENSP00000459725.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tmem88a | Danio rerio | Structure: myeloid cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- multicellular organism development
- Wnt signaling pathway
- protein stabilization
- protein localization to plasma membrane
- negative regulation of canonical Wnt signaling pathway
Molecular Function
- protein binding
- PDZ domain binding
Cellular Component
- cytosol
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301599
- Coding exons
- 2
- Length
- 1035
- Individuals with no LoFs
- 125361
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125379
- p
- 0.0000718
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.337 | 94 | 104 | 0.907 | 0.00000641 | 946 |
| Missense (PolyPhen) | 35 | 45.021 | 0.77742 | 415 | ||
| Synonymous | -0.722 | 54 | 47.7 | 1.13 | 0.00000283 | 391 |
| Loss of Function | 1.31 | 1 | 3.72 | 0.269 | 2.03e-7 | 31 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000091 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000062 | 0.000047 | rare |
| European (Non-Finnish) | 0.000083 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the Wnt/beta-catenin signaling pathway. Crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte development. {ECO:0000269|PubMed:23924634}.;
Intolerance Scores
- LoFtool
- 0.423
- RVIS EVS
- 0.95
- RVIS percentile EVS
- 89.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.326
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |