GeneBe

KRT9

protein-coding

keratin 9, the group of Keratins, type I

Gene summary

This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000226.4

Inheritance

AD

ClinVar variants

P:25U:119B:55

Top phenotype

Palmoplantar keratoderma, epidermolytic 1

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr17:41,565,836-41,572,059

External References & Databases

Ensembl (ENSG00000171403)NCBI Gene (3857)OMIM (607606)HGNC:6447GenCCUniProt (P35527)AlphaFoldClinVar (KRT9)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epidermolytic palmoplantar keratoderma, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007758

Submitter: Labcorp Genetics (formerly Invitae)

epidermolytic palmoplantar keratoderma, 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007758

Submitter: Ambry Genetics

epidermolytic palmoplantar keratoderma, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007758

Submitter: PanelApp Australia

epidermolytic palmoplantar keratoderma, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007758

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Palmoplantar keratoderma, epidermolytic 1AD

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: 7528239; 7512862; 7511021; 9856842; 12192490; 12838553; 17074468; 19106041Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KRT9 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 107
Inborn genetic diseasesTotal: 81
Palmoplantar keratoderma, epidermolyticTotal: 61
Epidermolytic palmoplantar keratoderma, 1Total: 26
KRT9-related disorderTotal: 25
not specifiedTotal: 25
Prostate cancerTotal: 1
Palmoplantar keratodermasTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000226.4. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
31
clinvar
2
clinvar
 38
missense
10
clinvar
14
clinvar
107
clinvar
21
clinvar
1
clinvar
 153
nonsense
1
clinvar
3
clinvar
 4
start loss
0
frameshift
4
clinvar
 4
splice donor/acceptor (+/-2bp)
0
Total1114119523199

Highest pathogenic variant AF is 0.000004104961

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000226.4RefSeqNP_000217.27MANE Select
ENST00000246662.9EnsemblENSP00000246662.47MANE Select
ENST00000588431.1EnsemblENSP00000467932.16Standard
ENST00000588431.2EnsemblENSP00000467932.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Estrogen signaling pathway - Homo sapiens (human)
  • Keratinization
  • Developmental Biology

Biological Process

  • spermatogenesis
  • epidermis development
  • keratinization
  • skin development
  • intermediate filament organization

Molecular Function

  • structural constituent of cytoskeleton

Cellular Component

  • extracellular space
  • nucleus
  • cytosol
  • intermediate filament
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000246662
Coding exons
7
Length
6215
Individuals with no LoFs
125709
Homozygous LoFs
0
Heterozygous LoFs
39
Defined
125748
p
0.000155
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1993383480.9700.00001984002
Missense (PolyPhen)6881.9770.82951125
Synonymous-0.2871341301.030.000007621252
Loss of Function1.841322.40.5800.00000113284

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000170.00017rare
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000150.00015rare
South Asian0.000370.00036rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: May serve an important special function either in the mature palmar and plantar skin tissue or in the morphogenetic program of the formation of these tissues. Plays a role in keratin filament assembly. {ECO:0000269|PubMed:10218578, ECO:0000269|PubMed:7507869}.;
Disease
DISEASE: Keratoderma, palmoplantar, epidermolytic (EPPK) [MIM:144200]: A dermatological disorder characterized by diffuse thickening of the epidermis on the entire surface of palms and soles sharply bordered with erythematous margins. Some patients may present knuckle pads, thick pads of skin appearing over the proximal phalangeal joints. {ECO:0000269|PubMed:10632938, ECO:0000269|PubMed:10844507, ECO:0000269|PubMed:12072061, ECO:0000269|PubMed:12192490, ECO:0000269|PubMed:12838553, ECO:0000269|PubMed:12926810, ECO:0000269|PubMed:14675368, ECO:0000269|PubMed:15099359, ECO:0000269|PubMed:15115518, ECO:0000269|PubMed:15605275, ECO:0000269|PubMed:16911293, ECO:0000269|PubMed:16961539, ECO:0000269|PubMed:19874353, ECO:0000269|PubMed:20964665, ECO:0000269|PubMed:21715251, ECO:0000269|PubMed:7511021, ECO:0000269|PubMed:7512862, ECO:0000269|PubMed:7516304, ECO:0000269|PubMed:7523529, ECO:0000269|PubMed:7532199, ECO:0000269|PubMed:8647270, ECO:0000269|PubMed:9204965, ECO:0000269|PubMed:9856842}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.199

Intolerance Scores

LoFtool
0.109
RVIS EVS
-1.2
RVIS percentile EVS
5.83

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.533

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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