TCHH
protein-codingtrichohyalin, the group of S100 fused type protein family|EF-hand domain containing
Gene summary
The protein encoded by this gene forms crosslinked complexes with itself and keratin intermediate filaments to provide mechanical strength to the hair follicle inner root sheath. The encoded protein also is important for structural integrity of the filiform papillae of the tongue. Defects in this gene are a cause of uncombable hair syndrome. [provided by RefSeq, Feb 2017]
- THH
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014990
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014990
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: The clinical relevance of the condition is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TCHH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007113.4. 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 | 19 | 1 | 20 | |||
| missense | 423 | 29 | 3 | 455 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 3 | 425 | 50 | 4 | 482 |
Highest pathogenic variant AF is 0.0003795474
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009044.2 | 2 | MANE Select | |
| Ensembl | ENSP00000480484.1 | 2 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
- Formation of the cornified envelope
Biological Process
- biological_process
- intermediate filament organization
- cornification
Molecular Function
- calcium ion binding
- transition metal ion binding
Cellular Component
- cornified envelope
- cytosol
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368804
- Coding exons
- 2
- Length
- 7764
- Individuals with no LoFs
- 124070
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 744
- Defined
- 124817
- p
- 0.00300
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -6.60 | 1509 | 940 | 1.61 | 0.0000581 | 12680 |
| Missense (PolyPhen) | 3 | 2.1152 | 1.4183 | 19 | ||
| Synonymous | -5.26 | 543 | 408 | 1.33 | 0.0000208 | 3404 |
| Loss of Function | 1.68 | 44 | 57.7 | 0.762 | 0.00000277 | 619 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.0023 | 0.0018 | notable |
| Ashkenazi Jewish | 0.00036 | 0.00030 | rare |
| East Asian | 0.0012 | 0.0012 | notable |
| Finnish | 0.0017 | 0.0015 | notable |
| European (Non-Finnish) | 0.0056 | 0.0050 | notable |
| South Asian | 0.00095 | 0.00092 | rare |
| Other | 0.0023 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Intermediate filament-associated protein that associates in regular arrays with keratin intermediate filaments (KIF) of the inner root sheath cells of the hair follicle and the granular layer of the epidermis. It later becomes cross-linked to KIF by isodipeptide bonds. It may serve as scaffold protein, together with involucrin, in the organization of the cell envelope or even anchor the cell envelope to the KIF network. It may be involved in its own calcium-dependent postsynthetic processing during terminal differentiation.;
- Disease
- DISEASE: Uncombable hair syndrome 3 (UHS3) [MIM:617252]: A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. {ECO:0000269|PubMed:27866708}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.983
- RVIS EVS
- 1.54
- RVIS percentile EVS
- 95.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.663
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |