Amelogenesis imperfecta

Gene: KLK4

Green List (high evidence)

KLK4 (kallikrein related peptidase 4)
EnsemblGeneIds (GRCh38): ENSG00000167749
EnsemblGeneIds (GRCh37): ENSG00000167749
OMIM: 603767, Gene2Phenotype
KLK4 is in 1 panel

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: August 16th 2017.
16 Aug 2017, 9:33 a.m.
Comment on list classification: Updated rating from Amber to Green: Green expert review plus on Leeds diagnostic panel. 2 variants (2 African American siblings and an unrelated Turkish girl) reported in OMIM (W153X and 1bp deletion c.245delG). 2 further variants curated in LOVD and reported by Claire Smith (frameshift at p.Ser207 and the 4th KLK4 variant (c.632delT) which may be a common cause of AI in the Pakistani population (PMID:28611678).
16 Aug 2017, 9:32 a.m.
Comment on mode of inheritance: Biallelic MOI also supported by OMIM.
16 Aug 2017, 9:23 a.m.

Claire Smith (University of Leeds)

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Associated with hypomaturation AI. KLK4 mutations cause autosomal recessive hypomaturation AI (Hart et al., 2004). All four KLK4 variants reported so far are either nonsense or frameshift mutations. However, only two of the four are predicted to lead to NMD. Of the two frameshift mutations affecting codons in the final exon, and therefore not expected to undergo NMD, one alters one of the three catalytic residues, p.S207, essential to the function of all kallikrein enzymes. The c.632delT variant, reported to occur at a frequency of 0.15% in the South Asian population, has been reported in five Pakistani families with hypomaturation AI. See KLK4 LOVD: http://dna2.leeds.ac.uk/LOVD/genes/KLK4
3 Aug 2017, 1:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, type IIA1 204700

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IIA1, 204700
  • Amelogenesis Imperfecta, Hypomaturation Type, IIA1, 204700
OMIM
603767
Clinvar variants
Variants in KLK4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith

16 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

16 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

16 Aug 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for KLK4 was changed to BIALLELIC, autosomal or pseudoautosomal

16 Aug 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for KLK4 were set to 15235027; 23355523; 26124219; 28611678

16 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for KLK4 were set to Amelogenesis imperfecta, type IIA1, 204700; Amelogenesis Imperfecta, Hypomaturation Type, IIA1, 204700

8 Jun 2017, Gel status: 2

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

KLK4 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene KLK4 was set to BIALLELIC, autosomal or pseudoautosomal

8 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

KLK4 was added to Amelogenesis Imperfectapanel. Source: Radboud University Medical Center, Nijmegen

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

KLK4 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

KLK4 was created by rfoulger