Monogenic short stature

Gene: NLRP5

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #620333) and the OMIM record was last accessed on 18 December 2025.

Created: 18 Dec 2025, 10:07 p.m. | Last Modified: 18 Dec 2025, 10:07 p.m.

Panel Version: 1.29

Submitted on behalf of NHS GMS "This gene does not go on the panel as linked to MLID and suggest separate panel for this. Genes NLRP5, NLRP7, PAD16, NLRP2 & KHDC3L"

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

Green List (high evidence)

Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder

Created: 21 Apr 2021, 2:39 p.m. | Last Modified: 21 Apr 2021, 2:41 p.m.

Panel Version: 1.59

Comment on list classification: Based on review from Professor Karen Temple (Clinical Genetics, University Hospital Southampton NHS Foundation Trust) for the involvement of NLRP5 variants in Multi Locus Imprinting Disturbance

Created: 1 Feb 2021, 8:49 a.m. | Last Modified: 2 Feb 2021, 2:43 p.m.

Panel Version: 1.52

Green List (high evidence)

A number of patients with IUGR and failure of catch up have an imprinting error (withiin the spectrum of Silver Russell syndrome, temple syndrome) that is caused by mutations in NLRP5 in the MOTHER of the patient. Note that LOF mutations (homozygous or heterozygous mutations) identified in the mother would lead to further patient testing for multilocus imprinting disturbance through methylation testing.
Sources: Expert list

Created: 29 Jan 2021, 11:06 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
IUGR; Short stature; Failure to thrive; body asymmetry

Publications

• Louise E Docherty, Faisal I Rezwan, Rebecca L Poole, Claire LS Turner, Emma Kivuva, Eamonn R Maher, Sarah F Smithson, Julian P Hamilton-Shield, Michal Patalan, Maria Gizewska, Jaroslaw Peregud-Pogorzelski, Jasmin Beygo, Karin Buiting, Bernhard Horsthemke, Lukas Soellner, Matthias Begemann, Thomas Eggermann, Emma Baple, Sahar Mansour, I Karen Temple, and Deborah JG Mackay, Mutations in NLRP5 are associated with reproductive wastage and multi-locus imprinting disorders in humans. Nature Communications: 2015, 6: 8086. PMID: 26323243 DOI: 10.1038/ncomms9086. PMC4568303 Begemann, M., Rezwan, F. I., Beygo, J., Docherty, L. E., Kolarova, J., Schroeder, C., Karin Buiting, Kamal Chokkalingam, Franziska Degenhardt, Emma L Wakeling, Stephanie Kleinle, Daniela González Fassrainer, Barbara Oehl-Jaschkowitz, Claire L S Turner, Michal Patalan, Maria Gizewska, Gerhard Binder, Can Thi Bich Ngoc, Vu Chi Dung, Sarju G Mehta, Gareth Baynam, Julian P Hamilton-Shield, Sara Aljareh, Oluwakemi Lokulo-Sodipe, Rachel Horton, Reiner Siebert, Miriam Elbracht, I Karen Temple, Thomas Eggermann, Mackay, D. J. G.. Maternal variants in NLRP and other maternal-effect proteins are associated with multi-locus imprinting disturbance in offspring. Journal of Medical Genetics, 2018 55:497–504. PMID: 29574422 DOI: 10.1136/jmedgenet-2017-105190
• PMC6047157