KRT85

protein-coding

keratin 85, 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. [provided by RefSeq, Jul 2008]

Previous symbols:

KRTHB5

MANE transcript

NM_002283.4

Inheritance

AR, AD

ClinVar variants

P:1U:109B:38

Top phenotype

Ectodermal dysplasia 4, hair-nail type

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr12:52,360,006-52,367,481

External References & Databases

Ensembl (ENSG00000135443)

Transcript & Mutation Effects

hg38 • Region Span ~7.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ectodermal dysplasia 4, hair/nail typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011177

Submitter: G2P

pure hair and nail ectodermal dysplasiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019071

Submitter: Orphanet

ectodermal dysplasia 4, hair/nail typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011177

Submitter: Ambry Genetics

ectodermal dysplasia 4, hair/nail typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011177

Submitter: Labcorp Genetics (formerly Invitae)

ectodermal dysplasia 4, hair/nail typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011177

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ectodermal dysplasia 4, hair-nail typeAR

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: 16525032; 19865094

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT85 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 60

KRT85-related disorderTotal: 14

Ectodermal dysplasia 4, hair/nail typeTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002283.4. 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				20 clinvar	8 clinvar	28
missense			107 clinvar	5 clinvar	5 clinvar	117
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	109	25	13	148

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002283.4	RefSeq	NP_002274.1	9	MANE Select
ENST00000257901.7	Ensembl	ENSP00000257901.3	9	MANE Select
NM_001300810.1	RefSeq	NP_001287739.1	7	Standard
ENST00000544265.1	Ensembl	ENSP00000440240.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology

Biological Process

epidermis development
keratinization
cornification

Molecular Function

structural molecule activity

Cellular Component

extracellular space
cytosol
keratin filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257901
Coding exons: 9
Length: 7476
Individuals with no LoFs: 125563
Homozygous LoFs: 0
Heterozygous LoFs: 185
Defined: 125748
p: 0.000736

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.395	302	322	0.938	0.0000239	3283
Missense (PolyPhen)		141	153.69	0.91742		1606
Synonymous	-0.476	142	135	1.05	0.0000101	1032
Loss of Function	2.23	13	25.0	0.520	0.00000146	273

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0019	0.0018	notable
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0012	0.0012	notable
Finnish	0.0022	0.0022	notable
European (Non-Finnish)	0.00059	0.00059	rare
South Asian	0.00026	0.00026	rare
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.195
RVIS EVS: -0.46
RVIS percentile EVS: 23.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.704

Gene Damage Prediction

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