GeneBe

KRT74

keratin 74, the group of Keratins, type II

Basic information

Region (hg38): 12:52565782-52573843

Links

ENSG00000170484 ∙ NCBI:121391 ∙ OMIM:608248 ∙ HGNC:28929 ∙ Uniprot:Q7RTS7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypotrichosis 3 (Moderate), mode of inheritance: AD
  • isolated familial wooly hair disorder (Supportive), mode of inheritance: AD
  • pure hair and nail ectodermal dysplasia (Supportive), mode of inheritance: AD
  • hypotrichosis simplex of the scalp (Supportive), mode of inheritance: AD
  • autosomal dominant wooly hair (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ectodermal dysplasia 7, hair/nail type; Hypotrichosis 3; Woolly hair, autosomal dominantADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic20346438; 20409997; 21188418; 24714551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KRT74 gene.

  • not_specified (106 variants)
  • not_provided (86 variants)
  • KRT74-related_disorder (13 variants)
  • Autosomal_dominant_wooly_hair (5 variants)
  • Hypotrichosis_3 (3 variants)
  • Ectodermal_dysplasia_7,_hair/nail_type (2 variants)
  • Ectodermal_dysplasia_4,_hair/nail_type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KRT74 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000175053.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
11
clinvar
11
clinvar
 23
missense
2
clinvar
109
clinvar
22
clinvar
11
clinvar
 144
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total 3 0 113 33 23

Highest pathogenic variant AF is 0.00000123912

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KRT74protein_codingprotein_codingENST00000305620 98044
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.12e-140.0085312532924171257480.00167
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.203633041.190.00001983452
Missense in Polyphen9379.4961.16991144
Synonymous-1.661521281.190.000008271066
Loss of Function-0.3712018.31.098.05e-7239

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.006720.00660
Ashkenazi Jewish0.01020.0103
East Asian0.002280.00229
Finnish0.0001390.000139
European (Non-Finnish)0.0009060.000897
Middle Eastern0.002280.00229
South Asian0.00009800.0000980
Other0.003090.00294

dbNSFP

Source: dbNSFP

Function
FUNCTION: Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable). {ECO:0000305}.;
Disease
DISEASE: Hypotrichosis 3 (HYPT3) [MIM:613981]: A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. {ECO:0000269|PubMed:21188418}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ectodermal dysplasia 7, hair/nail type (ECTD7) [MIM:614929]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. Ectodermal dysplasia of the hair/nail type is characterized by hypotrichosis and nail dystrophy without non- ectodermal or other ectodermal manifestations. {ECO:0000269|PubMed:24714551}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Keratinization;Developmental Biology (Consensus)

Recessive Scores

pRec
0.112

Intolerance Scores

loftool
0.147
rvis_EVS
2.38
rvis_percentile_EVS
98.48

Haploinsufficiency Scores

pHI
0.148
hipred
N
hipred_score
0.146
ghis
0.430

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.664

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Krt74
Phenotype

Gene ontology

Biological process
keratinization;intermediate filament cytoskeleton organization;cornification
Cellular component
cytoplasm;cytosol;keratin filament;extracellular exosome
Molecular function
structural molecule activity;keratin filament binding