Details for: KRT81

Gene ID: 3887

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KRT81

Ensembl ID: ENSG00000205426

Description: keratin 81

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mammary gland epithelial cell CL0002327
    CSI 7.12
    rCSI 24.96%
    PRS 99.66
  • intraepithelial lymphocyte CL0002496
    CSI 5.06
    rCSI 13.78%
    PRS 99.67
  • group 3 innate lymphoid cell CL0001071
    CSI 3.62
    rCSI 2.72%
    PRS 99.51
  • innate lymphoid cell CL0001065
    CSI 2.65
    rCSI 5.47%
    PRS 96.82
  • basal cell of epidermis CL0002187
    CSI 1.97
    rCSI 3.49%
    PRS 89.24

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KRT81](/details-gene/3887), or Keratin 81, is a protein-coding gene that produces a type II intermediate filament protein, specifically a hair keratin. Its primary function is to provide structural integrity to epithelial cells, particularly within hair follicles. As a key component of keratin filaments, it is essential for the process of keratinization, which is critical for forming the protective outer layers of skin appendages. Clinically, mutations in [KRT81](/details-gene/3887) are well-documented as a cause of monilethrix ([158000](https://omim.org/entry/158000)), an inherited hair shaft disorder characterized by beaded, fragile hair [Link](https://doi.org/10.1007/s004390050607). While its role in hair and skin is established, expression data indicates its highest significance in [mammary gland epithelial cell](/details-cell/CL0002327)s, with notable expression also observed in specific immune cell populations, suggesting functions beyond hair formation. ## Cellular Roles and Expression Landscape The expression profile of [KRT81](/details-gene/3887) highlights its central role as a structural protein in specialized epithelial tissues, with intriguing signals in the immune system. **Overall**, the gene's significance is highest in [mammary gland epithelial cell](/details-cell/CL0002327) (CSI: 7.12), suggesting a potentially important, though less characterized, structural role in mammary gland biology. Its expression in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.97) is highly consistent with its known function in hair follicles and skin, as these cells are precursors to keratinized structures [Link](https://doi.org/10.1046/j.1523-1747.1998.00097.x). Unexpectedly, [KRT81](/details-gene/3887) shows significant expression in several lymphocyte populations, including [intraepithelial lymphocyte](/details-cell/CL0002496)s (CSI: 5.06), [group 3 innate lymphoid cell](/details-cell/CL0001071)s (CSI: 3.62), and the broader [innate lymphoid cell](/details-cell/CL0001065) category (CSI: 2.65). As these immune cells reside within or adjacent to epithelial barriers, this pattern may indicate a non-canonical role for [KRT81](/details-gene/3887) in maintaining cytoskeletal integrity during cell migration, or in mediating physical interactions with surrounding keratin-expressing epithelial cells. ## Pathways and Molecular Function The molecular functions of [KRT81](/details-gene/3887) are centered on its role as a structural biopolymer. Its involvement in the Reactome pathways [Keratinization](/details-pathway/R-HSA-6805567) and [Formation of the cornified envelope](/details-pathway/R-HSA-6809371) directly underpins its biological importance in epidermal tissues. This is further supported by its annotation to Gene Ontology (GO) terms such as [Intermediate filament organization](/details-ontology/GO0045109) and being a [Structural constituent of skin epidermis](/details-ontology/GO0030280). Functionally, [KRT81](/details-gene/3887) polymerizes with type I keratins to form the keratin filament network ([GO:0045095](https://www.ebi.ac.uk/QuickGO/term/GO:0045095)), a key component of the cellular cytoskeleton that provides mechanical resilience. The pathological consequences of disrupting this network are evident in monilethrix, where mutations in [KRT81](/details-gene/3887) lead to a compromised hair shaft structure [Link](https://doi.org/10.1111/exd.12624). ## Research Directions The expression data for [KRT81](/details-gene/3887) reinforces its known function while also pointing toward novel biological contexts, providing fertile ground for future research. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [KRT81](/details-gene/3887) in [mammary gland epithelial cell](/details-cell/CL0002327)s suggests it may contribute to the structural integrity of mammary ducts, and its dysregulation could be involved in the cellular changes associated with breast pathologies. 2. The expression of [KRT81](/details-gene/3887) in [intraepithelial lymphocyte](/details-cell/CL0002496)s and [group 3 innate lymphoid cell](/details-cell/CL0001071)s points to a non-canonical role in immune cell biology. It may be required for maintaining cellular shape and motility as these cells navigate the tight junctions of epithelial barriers. To test the second, more novel hypothesis, a key experiment could be designed. To investigate the function of [KRT81](/details-gene/3887) in ILCs, a conditional knockout mouse model could be generated in which the gene is specifically deleted in ILC3s (e.g., using a *Rorc*-Cre driver). The ability of these KRT81-deficient ILC3s to populate and function within the gut epithelium could be assessed following an intestinal challenge, such as infection with *Citrobacter rodentium*. Cell localization and morphology could be analyzed by immunofluorescence microscopy, while functional output could be measured by cytokine profiling of isolated cells. Regarding therapeutic potential, [KRT81](/details-gene/3887) is a challenging target. As an intracellular structural protein, it is not readily accessible to antibody-based therapies. For the monogenic disorder monilethrix ([158000](https://omim.org/entry/158000)), therapeutic avenues would more likely involve genetic-based strategies, such as gene therapy or RNA interference to silence the mutant allele, rather than traditional pharmacological inhibition or activation.

Genular Protein ID: 3691718819

Symbol: KRT81_HUMAN

Name: Keratin, type II cuticular Hb1

UniProtKB Accession Codes:

Q14533 Q14846 Q16274 Q17R48 Q8WU52 Q9BR74

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 1 ExpressionAtlas 1 GO 6 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9457912

Title: Characterization and chromosomal localization of human hair-specific keratin genes and comparative expression during the hair growth cycle.

PubMed ID: 9457912

DOI: 10.1046/j.1523-1747.1998.00097.x

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7556444

Title: Sequence data and chromosomal localization of human type I and type II hair keratin genes.

PubMed ID: 7556444

DOI: 10.1006/excr.1995.1326

PubMed ID: 7490069

Title: Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17.

PubMed ID: 7490069

DOI: 10.1006/geno.1995.1163

PubMed ID: 7528047

Title: Sequence and expression of human hair keratin genes.

PubMed ID: 7528047

DOI: 10.1016/0923-1811(94)90046-9

PubMed ID: 9402962

Title: A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix.

PubMed ID: 9402962

DOI: 10.1007/s004390050607

PubMed ID: 9665406

Title: A variable monilethrix phenotype associated with a novel mutation, Glu402Lys, in the helix termination motif of the type II hair keratin hHb1.

PubMed ID: 9665406

DOI: 10.1046/j.1523-1747.1998.00234.x

PubMed ID: 25557232

Title: Novel KRT83 and KRT86 mutations associated with monilethrix.

PubMed ID: 25557232

DOI: 10.1111/exd.12624

Sequence Information:

  • Length: 505
  • Mass: 54928
  • Checksum: 6CD174038C3B6C27
  • Sequence:
    • MTCGSGFGGR AFSCISACGP RPGRCCITAA PYRGISCYRG LTGGFGSHSV CGGFRAGSCG 
RSFGYRSGGV CGPSPPCITT VSVNESLLTP LNLEIDPNAQ CVKQEEKEQI KSLNSRFAAF 
IDKVRFLEQQ NKLLETKLQF YQNRECCQSN LEPLFEGYIE TLRREAECVE ADSGRLASEL 
NHVQEVLEGY KKKYEEEVSL RATAENEFVA LKKDVDCAYL RKSDLEANVE ALIQEIDFLR 
RLYEEEILIL QSHISDTSVV VKLDNSRDLN MDCIIAEIKA QYDDIVTRSR AEAESWYRSK 
CEEMKATVIR HGETLRRTKE EINELNRMIQ RLTAEVENAK CQNSKLEAAV AQSEQQGEAA 
LSDARCKLAE LEGALQKAKQ DMACLIREYQ EVMNSKLGLD IEIATYRRLL EGEEQRLCEG 
IGAVNVCVSS SRGGVVCGDL CVSGSRPVTG SVCSAPCNGN VAVSTGLCAP CGQLNTTCGG 
GSCGVGSCGI SSLGVGSCGS SCRKC