KRT86

protein-coding

keratin 86, the group of Keratins, type II

Gene summary

This gene encodes a type II keratin protein, which heterodimerizes with type I keratins to form hair and nails. This gene is present in a cluster of related genes and pseudogenes on chromosome 12. Mutations in this gene have been observed in patients with the hair disease monilethrix. [provided by RefSeq, Feb 2016]

Previous symbols:

KRTHB6

MANE transcript

NM_001320198.2

Inheritance

ClinVar variants

P:6U:85B:18

Top phenotype

Monilethrix

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr12:52,249,300-52,309,163

External References & Databases

Ensembl (ENSG00000170442)

Transcript & Mutation Effects

hg38 • Region Span ~59.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

monilethrix-1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700343

Submitter: G2P

monilethrix-1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700343

Submitter: PanelApp Australia

monilethrixMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008009

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

monilethrixSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008009

Submitter: Orphanet

monilethrixSTRONG

Inheritance Pattern: AD

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: 9241275; 9665406; 10878478; 15744029; 19400537; 22568869; 22670615

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT86 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 113

Inborn genetic diseasesTotal: 80

not providedTotal: 52

MonilethrixTotal: 10

Monilethrix-1Total: 8

Monilethrix-2Total: 2

KRT81-related disorderTotal: 2

KRT86-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001320198.2. 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			2 clinvar	11 clinvar	1 clinvar	14
missense	5 clinvar	1 clinvar	82 clinvar	5 clinvar	1 clinvar	94
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	1	85	16	2	109

Highest pathogenic variant AF is 0.0011609466

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001320198.2	RefSeq	NP_001307127.1	9	MANE Select
ENST00000423955.7	Ensembl	ENSP00000444533.1	9	MANE Select
ENST00000293525.5	Ensembl	ENSP00000293525.5	9	Standard
ENST00000553310.6	Ensembl	ENSP00000452237.3	2	Standard

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: ENST00000293525
Coding exons: 9
Length: 59864
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.27	309	252	1.22	0.0000178	3120
Missense (PolyPhen)		98	86.925	1.1274		1256
Synonymous	-1.87	134	109	1.23	0.00000791	957
Loss of Function	0.980	12	16.3	0.738	7.17e-7	256

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00052	0.00052	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.148

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.412

Gene Damage Prediction

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