KRT75
protein-codingkeratin 75, the group of Keratins, type II
Gene summary
This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. This gene is expressed in the companion layer, upper germinative matrix region of the hair follicle, and medulla of the hair shaft. The encoded protein plays an essential role in hair and nail formation. Variations in this gene have been associated with the hair disorders pseudofolliculitis barbae (PFB) and loose anagen hair syndrome (LAHS). [provided by RefSeq, Oct 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KRT75 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004693.3. 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 | 8 | 8 | ||||
| missense | 85 | 6 | 3 | 94 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 85 | 14 | 3 | 102 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004684.2 | 9 | MANE Select | |
| Ensembl | ENSP00000252245.5 | 9 | MANE Select | |
| Ensembl | ENSP00000802601.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
Biological Process
- hematopoietic progenitor cell differentiation
- keratinization
- cornification
Molecular Function
- structural molecule activity
Cellular Component
- cytosol
- intermediate filament
- keratin filament
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000252245
- Coding exons
- 9
- Length
- 10456
- Individuals with no LoFs
- 125582
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 165
- Defined
- 125748
- p
- 0.000660
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.966 | 364 | 316 | 1.15 | 0.0000202 | 3581 |
| Missense (PolyPhen) | 110 | 93.861 | 1.172 | 1261 | ||
| Synonymous | -1.72 | 152 | 127 | 1.19 | 0.00000805 | 1132 |
| Loss of Function | 1.50 | 15 | 22.7 | 0.660 | 0.00000125 | 251 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00093 | 0.00092 | rare |
| South Asian | 0.00082 | 0.00078 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a central role in hair and nail formation. Essential component of keratin intermediate filaments in the companion layer of the hair follicle.;
- Disease
- DISEASE: Loose anagen hair syndrome (LAHS) [MIM:600628]: In LAHS, anagen hairs are easily pulled from the scalp. The hair is relatively sparse and does not grow long. Hair of fair color and hair shafts of reduced caliber, and an early age of onset are features. Usually the hairs are not fragile and there are no areas of breakage. {ECO:0000269|PubMed:11939812}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.170
- RVIS EVS
- 2.52
- RVIS percentile EVS
- 98.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.129
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |