Fetal anomalies
Gene: NEK9

NEK9 (NIMA related kinase 9)
EnsemblGeneIds (GRCh38): ENSG00000119638
EnsemblGeneIds (GRCh37): ENSG00000119638
OMIM: 609798, Gene2Phenotype
NEK9 is in 3 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 16 Mar 2022, 3:29 p.m. | Last Modified: 16 Mar 2022, 3:29 p.m.

Panel Version: 1.842

Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag). At least 3 unrelated families presenting a similar fetally-relevant phenotype in association with different biallelic variants in this gene.

NEK9 is associated with relevant phenotypes in OMIM (MIM# 614262 and 617022) but currently is not in Gene2Phenotype.
Created: 18 Jan 2021, 2:58 p.m. | Last Modified: 18 Jan 2021, 2:58 p.m.

Panel Version: 1.158

Created: 18 Jan 2021, 2:58 p.m.
Last Modified: 18 Jan 2021, 2:58 p.m.
Panel version: 1.842

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

Deden et al (2020) report a further family with two consecutive prenatal presentations with compound heterozygous NEK9 variants. Both fetuses had arthrogryposis.

Both variants were reported as VUS when detected in the first fetus, which initially presented with 'short long bones, bowed femur, micrognathia, talipes and deviated hand' but re-evaluated after the phenotype progressed to arthrogryposis and then the next pregnancy showed the same ultrasound abnormalities and the same compound het variants. At this point the authors felt this represented a conclusive diagnosis.
Created: 22 Oct 2020, 6:07 p.m. | Last Modified: 22 Oct 2020, 6:07 p.m.

Panel Version: 1.107

Shaheen et al 2016 reported 3 affected individuals in one consanguineous Saudi family with arthrogryposis apparent since early childhood, avascular necrosis of the hip (Perthes disease), and upward gaze palsy.

Casey et al 2016 reported 4 affected fetuses in two Irish Traveller families: phenotype = fetal akinesia, shortening of all long bones, multiple contractures, rib anomalies, thoracic dysplasia, pulmonary hypoplasia. The two families are thought to be distantly related to one another.

Therefore, this represents two affected families so probably not enough evidence for Green rating yet until more cases reported.
Created: 6 Oct 2020, 3:38 p.m. | Last Modified: 6 Oct 2020, 3:38 p.m.

Panel Version: 1.98

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis; short long bones

Publications

Created: 6 Oct 2020, 3:38 p.m.
Last Modified: 6 Oct 2020, 3:38 p.m.
Panel version: 1.107

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable.
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.9

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
PAGE Additional Gene List

Phenotypes

?Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262
Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660
Lethal congenital contracture syndrome 10, OMIM:617022
NEK9-related lethal skeletal dysplasia, MONDO:0014870

OMIM

609798

Clinvar variants

Variants in NEK9

Penetrance

None

Publications

Panels with this gene