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 20 panels

4 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Created: 31 Jan 2019, 10:39 a.m.
Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: NPC1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 7 Jan 2019, 4:42 p.m.

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

31 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

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

14 Jan 2019, Gel status: 4

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

Ivone Leong (Genomics England Curator)

Source Other was added to NPC1. Mode of inheritance for gene NPC1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Niemann-Pick disease, type D, 257220; Niemann-Pick disease type C1, 257220; Neonatal and Adult Cholestasis for gene: NPC1 Publications for gene NPC1 were changed from to 9634529; 10480349; 11545687; 10521290; 9211849; 24135395; 12554680; 11754101

7 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to NPC1. Rating Changed from Red List (low evidence) to Green List (high evidence)

7 Jan 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: NPC1 was added gene: NPC1 was added to Cholestasis. Sources: NHS GMS Mode of inheritance for gene: NPC1 was set to