TMCO4
protein-codingtransmembrane and coiled-coil domains 4
Gene summary
Predicted to be located in 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 ~117.7 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 TMCO4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181719.7. 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 | 1 | ||||
| missense | 121 | 6 | 127 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 128 | 7 | 0 | 135 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_859070.3 | 13 | MANE Select | |
| Ensembl | ENSP00000294543.6 | 13 | MANE Select | |
| RefSeq | NP_001336041.1 | 13 | Standard | |
| RefSeq | NP_001336042.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Cellular Component
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294543
- Coding exons
- 13
- Length
- 117733
- Individuals with no LoFs
- 125181
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 566
- Defined
- 125748
- p
- 0.00226
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.181 | 377 | 387 | 0.974 | 0.0000232 | 4024 |
| Missense (PolyPhen) | 149 | 157.33 | 0.94708 | 1598 | ||
| Synonymous | 0.132 | 169 | 171 | 0.987 | 0.0000114 | 1359 |
| Loss of Function | 0.174 | 31 | 32.1 | 0.967 | 0.00000189 | 324 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0018 | 0.0018 | notable |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0.0030 | 0.0030 | notable |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0.0011 | 0.0011 | notable |
| European (Non-Finnish) | 0.0030 | 0.0030 | notable |
| South Asian | 0.00073 | 0.00072 | rare |
| Other | 0.0028 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.934
- RVIS EVS
- 0.45
- RVIS percentile EVS
- 78.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.273
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |