Renal ciliopathies

Gene: KIF14

Amber List (moderate evidence)

KIF14 (kinesin family member 14)
EnsemblGeneIds (GRCh38): ENSG00000118193
EnsemblGeneIds (GRCh37): ENSG00000118193
OMIM: 611279, Gene2Phenotype
KIF14 is in 9 panels

5 reviews

Eleanor Williams (Genomics England Curator)

After discussion with the Genomics England clinical team it was decided to keep this gene as Amber with a watch list tag in view of most of the cases being of fetal relevance.
Created: 10 Jul 2020, 11:33 a.m. | Last Modified: 10 Jul 2020, 11:33 a.m.
Panel Version: 1.25

Catherine Snow (Genomics England)

I don't know

PMID:30388224 identified two families and reported on two further families which had already previously been reported upon in PMID: 28566479. All fetuses had biallelic pathogenic variants in KIF14 and had phenotypes within the spectrum of fetal forms of ciliopathies, Meckel–Gruber syndrome (MKS) - (intrauterine growth restriction, cystic kidneys and brain developmental defects, including cerebellar hypoplasia and vermis agenesis)

The paper also includes functional work on Zebrafish and reported that in vitro and in vivo analyses did not provide evidence of a direct role for KIF14 in ciliogenesis and suggested that loss of kif14 causes ciliopathy-like phenotypes through an accumulation of mitotic cells in ciliated tissues.

PMID: 28892560 - Reported on four individuals with variants in KIF14. 3/4 had no problems with renal system, 1/4 a German boy, was identified who had small kidneys with increased echogenicity. WES of the German patient revealed 2 compound heterozygous missense variants of KIF14. One of these variants (NM_014875.2;c.2545C>G;p.His849Asp) replaces a histidine by aspartic acid and is predicted to be disease causing. (NM_014875.2;c.3662G>T;p.Gly1221Val) introduces valine at a position of glycine that is not conserved among different animals. This variant affects the first nucleotide of exon 24, a position that might impair splicing.

PMID: 29343805 - Biallelic Variants in KIF14 Cause Intellectual Disability With Microcephaly. 4 unrelated individuals identified but all asymptomatic in the Genitourinary system.

Rating as Amber and requesting support from clinical team as unsure of KIF14 is relevant for this panel?
Created: 31 Mar 2020, 5:43 p.m. | Last Modified: 1 Apr 2020, 7:31 a.m.
Panel Version: 1.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Note additional four families reported 2019 plus zebrafish model.
Created: 3 Jan 2020, 4:27 a.m. | Last Modified: 3 Jan 2020, 4:27 a.m.
Panel Version: 1.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly; renal hypo/dysplasia

Publications

Variants in this GENE are reported as part of current diagnostic practice

Alice Gardham (Genomics England)

Comment when marking as ready: Only reported in one family
Created: 25 Jan 2017, 1:18 p.m.

Gabrielle Wheway (University of the West of England)

I don't know

Only one reported family, with two affected individuals. Compound heterozygous frameshift/premature stop and nonsense mutations. Mutations segregate with disease in compound heterozygous pattern. Mutations not found in any variant database checked.
Created: 5 Jul 2016, 2:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intrauterine growth restriction (IUGR); microcephaly; renal cystic dysplasia/agenesis; complex brain malformation; genitourinary malformation

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Orphanet
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • ?Meckel syndrome 12, 616258
  • complex brain malformation
  • ?Meckel syndrome 12
  • intrauterine growth restriction (IUGR)
  • microcephaly
  • Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome
  • genitourinary malformation
  • renal cystic dysplasia/agenesis
Tags
watchlist
OMIM
611279
Clinvar variants
Variants in KIF14
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Jul 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag watchlist tag was added to gene: KIF14.

21 May 2020, Gel status: 2

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: kif14 has been classified as Amber List (Moderate Evidence).

10 Jul 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: KIF14 was added gene: KIF14 was added to Renal ciliopathies. Sources: Other,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red,Orphanet Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF14 were set to 24128419 Phenotypes for gene: KIF14 were set to ?Meckel syndrome 12, 616258; complex brain malformation; ?Meckel syndrome 12; intrauterine growth restriction (IUGR); microcephaly; Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome; genitourinary malformation; renal cystic dysplasia/agenesis