KRT81

protein-coding

keratin 81, the group of Keratins, type II

Gene summary

The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin, as well as KRTHB3 and KRTHB6, is found primarily in the hair cortex. Mutations in this gene and KRTHB6 have been observed in patients with a rare dominant hair disease, monilethrix. Some human genome assemblies (example T2T-CHM13) have a non-coding version of the gene due to the presence of a SNP that introduces a premature stop codon after codon 281. [provided by RefSeq, Jan 2024]

Previous symbols:

KRTHB1

MANE transcript

NM_002281.4

Inheritance

ClinVar variants

P:3U:101B:19

Top phenotype

Monilethrix

gnomAD constraint

pLI —, LoF o/e 1.48

Max pathogenic AF

—

Genomic locus

chr12:52,285,913-52,291,534

External References & Databases

Ensembl (ENSG00000205426)

Transcript & Mutation Effects

hg38 • Region Span ~5.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

monilethrixSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008009

Submitter: Orphanet

monilethrix-1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700343

Submitter: PanelApp Australia

monilethrixMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008009

Submitter: G2P

monilethrixLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0008009

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

MonilethrixAD

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

Refs: 9665406; 15744029; 22628999

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT81 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 20

Monilethrix-1Total: 5

Monilethrix-2Total: 2

KRT81-related disorderTotal: 2

MonilethrixTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002281.4. 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				12 clinvar		12
missense	1 clinvar	1 clinvar	98 clinvar	4 clinvar	3 clinvar	107
nonsense		1 clinvar				1
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	2	101	16	3	123

Highest pathogenic variant AF is 0.0011609466

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002281.4	RefSeq	NP_002272.2	9	MANE Select
ENST00000327741.9	Ensembl	ENSP00000369349.4	9	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology

Biological Process

keratinization
cornification

Molecular Function

structural molecule activity
protein binding

Cellular Component

extracellular space
cytosol
keratin filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327741
Coding exons: 9
Length: 5622
Individuals with no LoFs: 125432
Homozygous LoFs: 2
Heterozygous LoFs: 314
Defined: 125748
p: 0.00126

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.295	280	266	1.05	0.0000200	3237
Missense (PolyPhen)		65	66.103	0.98331		1048
Synonymous	-1.42	139	119	1.17	0.00000981	1010
Loss of Function	-1.76	23	15.5	1.48	6.82e-7	256

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.0015	0.0014	notable
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.0018	0.0018	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.160

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.624

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium