Amyloidosis

Gene: NLRP3

Amber List (moderate evidence)

NLRP3 (NLR family pyrin domain containing 3)
EnsemblGeneIds (GRCh38): ENSG00000162711
EnsemblGeneIds (GRCh37): ENSG00000162711
OMIM: 606416, Gene2Phenotype
NLRP3 is in 11 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Created: 19 Oct 2020, 4:20 p.m. | Last Modified: 19 Oct 2020, 4:20 p.m.
Panel Version: 1.8

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green. NLRP3 was added to panel and rated Green by Zornitza Stark. Not yet in G2P but sufficient cases to support gene:disease association for NLRP3:Muckle-Wells syndrome, and approx 25-30% of MWS cases have an AA amyloidosis phenotype. Cases of NRLP3 variants in amyloidosis patients reported in PMIDs 30431487, 11992256. In summary: sufficient evidence to support association with MWS, and 25-30% of MWS patients have amyloidosis.
Created: 25 Mar 2020, 10:09 p.m. | Last Modified: 25 Mar 2020, 10:09 p.m.
Panel Version: 1.7
PMID:11992256 (Dode et al., 2002) identify NLRP3 (CIAS1) variants in 9 unrelated families with MWS. AA amyloidosis is recorded amongst the phenotypes in family 1 (R260W variant).
Created: 25 Mar 2020, 9:57 p.m. | Last Modified: 25 Mar 2020, 9:57 p.m.
Panel Version: 1.6
PMID:30431487 (Pandiarajan et al., 2018) report a 10-yr old child with nephrotic syndrome. The patient had a NLRP3 variant (c.1055C>T, p.Ala352Val) and features including AA amyloidosis.
Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:31057541 (Fingerhutová et al. 2019) report 1 family (11 individuals) with MWS and a p.Ala441Val variant in NLRP3. 2 patients aged over 50 years suffered with hearing loss and AA amyloidosis.
Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:27435956 (Villalba et al., 2016) report a 5-year old MWS patient with T348M variant in NLRP3. They report that amyloidosis and hearing loss is seen in ~25% of patients.
Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:28229991 (Hu et al., 2017) report a patient with periodic fever, arthralgia and skin lesions and an A92T variant in NLRP3 (p.D31V).
Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6
PMID:11687797 (Hoffman et al., 2001) studied 1 family (family 4, 2 individuals) with MWS and a de novo C1055T (p.A352V) variant in NLRP3 (aka CIAS1). Arthrogryposis isn't specifically mentioned amongst phenotypes.
Created: 25 Mar 2020, 9:47 p.m. | Last Modified: 25 Mar 2020, 9:47 p.m.
Panel Version: 1.6

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Renal amyloidosis described in this disorder.
Sources: Expert list
Created: 30 Jan 2020, 4:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Muckle-Wells syndrome

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Muckle-Wells syndrome, OMIM:191900
  • Renal amyloidosis
Tags
for-review to_be_confirmed_NHSE
OMIM
606416
Clinvar variants
Variants in NLRP3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Feb 2022, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag to_be_confirmed_NHSE tag was added to gene: NLRP3.

10 Jan 2022, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900; AA amyloidosis; renal amyloidosis to Muckle-Wells syndrome, OMIM:191900; Renal amyloidosis

19 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: nlrp3 has been classified as Amber List (Moderate Evidence).

24 Jun 2020, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: NLRP3.

25 Mar 2020, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: nlrp3 has been classified as Green List (High Evidence).

25 Mar 2020, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900 to Muckle-Wells syndrome, 191900; AA amyloidosis; renal amyloidosis

25 Mar 2020, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: NLRP3 were set to 11687797; 28229991; 27435956; 31057541

23 Mar 2020, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome, 191900 to Muckle-Wells syndrome, 191900

23 Mar 2020, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: NLRP3 were changed from Muckle-Wells syndrome to Muckle-Wells syndrome, 191900

30 Jan 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: NLRP3 was added gene: NLRP3 was added to Amyloidosis. Sources: Expert list Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NLRP3 were set to 11687797; 28229991; 27435956; 31057541 Phenotypes for gene: NLRP3 were set to Muckle-Wells syndrome Review for gene: NLRP3 was set to GREEN