Neonatal cholestasis

Gene: NPC1

Green List (high evidence)

NPC1 (NPC intracellular cholesterol transporter 1)
EnsemblGeneIds (GRCh38): ENSG00000141458
EnsemblGeneIds (GRCh37): ENSG00000141458
OMIM: 607623, Gene2Phenotype
NPC1 is in 19 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: Sufficient evidence to rate as green.
Created: 25 Jul 2018, 10:06 a.m.
Comment on publications: Added publications describing cases and phenotypes
Created: 25 Jul 2018, 10:05 a.m.
Comment on list classification: More than 3 unrelated cases with plausible disease-causing mutations in this gene.
Created: 25 Jul 2018, 10:02 a.m.
In OMIM this gene is associated with Niemann-Pick disease, type C1 and type D. One of the features of this disease is choleostasis (Mengel et al 2013 PMID: 24135395 ). Numerous cases (~50) reported with patients with Niemann-Pick disease type C1 and variants in this gene. In gene2phenotype there is a confirmed association of NPC1 with NIEMANN-PICK DISEASE, TYPE C1.
Created: 25 Jul 2018, 10:01 a.m.
Comment on phenotypes: Added Niemann-Pick disease, type D and MIM numbers.
Created: 25 Jul 2018, 9:38 a.m.

Jane Hartley (Birmingham Women and Children's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cholestasis; Niemann Pick C syndrome

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

Thalia Antoniadi (West Midlands Regional Genetics Laboratory)

Green List (high evidence)

All types of variants reported;
Rare gene in our cohort; 3 diagnoses in 205 patients tested (and we also test with MLPA)
Created: 4 Jun 2018, 1:12 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Niemann-Pick disease

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

History Filter Activity

3 Sep 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been subjected to extensive internal and external review.

25 Jul 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: NPC1 were set to Neonatal and Adult Cholestasis; Niemann-Pick disease type C1, 257220; Niemann-Pick disease, type D, 257220

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: npc1 has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: NPC1 were set to 9211849; 10480349; 10521290; 9634529; 9634529; 11545687; 11754101; 11754101; 12554680; 24135395

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: npc1 has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: NPC1 were set to Neonatal and Adult Cholestasis; Niemann-Pick disease type C1 257220; Niemann-Pick disease, type D 257220

21 Jun 2018, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

Victorian Clinical Genetics Services was added to NPC1. Panel: Cholestasis

18 May 2018, Gel status: 2

Added New Source, Set mode of inheritance, Set penetrance

Ellen McDonagh (Genomics England Curator)

UKGTN was added to NPC1. Panel: Cholestasis Model of inheritance for gene NPC1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene NPC1 were set to Neonatal and Adult Cholestasis, Niemann-Pick disease type C1

18 May 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NPC1 was added to Cholestasis panel. Sources: Emory Genetics Laboratory

18 May 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

NPC1 was created by Ellen McDonagh