TTYH1
protein-codingtweety family member 1, the group of Tweety family
Gene summary
This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-independent, volume-sensitive large conductance chloride(-) channel. Three transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.7 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 TTYH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020659.4. 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 | 5 | 3 | 8 | |||
| missense | 55 | 2 | 57 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 65 | 5 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065710.1 | 13 | MANE Select | |
| Ensembl | ENSP00000365713.3 | 13 | MANE Select | |
| RefSeq | NP_001005367.1 | 13 | Standard | |
| RefSeq | NP_001188390.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- mitotic cell cycle
- chloride transport
- iron ion transport
- cell-substrate adhesion
- ion transmembrane transport
Molecular Function
- intracellular calcium activated chloride channel activity
- chloride channel activity
- iron ion transmembrane transporter activity
- calcium ion binding
- volume-sensitive chloride channel activity
Cellular Component
- plasma membrane
- integral component of membrane
- smooth endoplasmic reticulum membrane
- filopodium membrane
- filopodium tip
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376531
- Coding exons
- 13
- Length
- 21688
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125745
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.384 | 241 | 258 | 0.933 | 0.0000144 | 2850 |
| Missense (PolyPhen) | 76 | 95.159 | 0.79866 | 1106 | ||
| Synonymous | -0.643 | 133 | 124 | 1.07 | 0.00000743 | 1016 |
| Loss of Function | 4.24 | 2 | 24.7 | 0.0808 | 0.00000116 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable chloride channel. May be involved in cell adhesion (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.654
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.169
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |