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Intellectual disability

Gene: NUP188

Amber List (moderate evidence)

NUP188 (nucleoporin 188)
EnsemblGeneIds (GRCh38): ENSG00000095319
EnsemblGeneIds (GRCh37): ENSG00000095319
OMIM: 615587, Gene2Phenotype
NUP188 is in 5 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: At least six unrelated families exhibiting a strikingly similar phenotype due to biallelic truncating variants in the NUP188 gene. Only 1/8 individuals survived beyond the first year of life and exhibited severe ID.

It is anticipated that other surviving patients would likely present the same phenotype; however, for now NUP188 will be rated Amber on the ID panel, awaiting further publications to corroborate the relevance of this manifestation.
Created: 29 Sep 2020, 10:09 a.m. | Last Modified: 29 Sep 2020, 10:09 a.m.
Panel Version: 3.356
Associated with Sandestig-Stefanova syndrome in OMIM, but not yet in G2P.

- PMID: 32021605 (2020) - Two unrelated patients with different homozygous nonsense variants of NUP188, c.287dupA, p.Tyr96* and c.337C>T, p.Gln113*, respectively. Authors note strikingly comparable phenotypes including pre- and postnatal microcephaly, trigonocephaly, congenital cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, ventricular septal defect, and brain MRI anomalies (ventriculomegaly, loss of periventricular white matter, thin corpus callosum, and delayed myelination). Both ultimately died as a result of central respiratory failure at the age of 67 and 140 days, respectively.

- PMID: 32275884 (2020) - Six individuals from four unrelated families with bi-allelic truncating variants in NUP188 and similar phenotypes characterised by prenatal-onset ventriculomegaly or suspected brain malformation (4/6), congenital cataracts (4/6), congenital heart defects (5/5), hypotonia (5/6), brain MRI abnormalities (6/6) including ventriculomegaly loss of white-matter, hypoplastic corpus callosum, and delayed myelination. Progressive microcephaly consistent with a neurodegenerative process was noted in at least 3 cases. All six patients died of respiratory failure or respiratory-related illness: five within the first seven months of life; and the sixth at 2 years and 7 months, who also has severe ID and was non-ambulatory.
Created: 29 Sep 2020, 9:54 a.m. | Last Modified: 29 Sep 2020, 9:54 a.m.
Panel Version: 3.355

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Sandestig-Stefanova syndrome, 618804


Zornitza Stark (Australian Genomics)

Green List (high evidence)

A total of 9 individuals reported with bi-allelic LoF variants and a consistent neurodevelopmental phenotype.
Created: 13 Apr 2020, 12:19 a.m. | Last Modified: 13 Apr 2020, 12:19 a.m.
Panel Version: 3.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

microcephaly; ID; cataract; structural brain abnormalities; hypoventilation


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

Konstantinos Varvagiannis (Other)

Red List (low evidence)

The gene was present in the current panel with red rating, though with no reviews.

In Pubmed there are no publications concerning a link with ID. One publication (PMID: 21282601) reports on a 9q34.11 148 kb duplication spanning NUP188 as well as few other genes found in an individual with d-TGA (dextro-transposition of great arteries). Eventual other phenotypes are not commented on. A further publication (PMID: 28611029) reports on an individual heterozygous for a splice-site SNV but only cardiovascular phenotype is commented on again (mitral valve prolapse - variant : NM_015354.2:c.4737+1G>T).

There are no publications when searching for the alternative gene symbol (KIAA1069), either.

There is no associated phenotype in OMIM or G2P.
The gene is not included in the SysID and SFARI databases.

The denovo-db lists 4 non-synonymous de novo variants in individuals with autism or mixed phenotype.
[ ]

In Decipher, all CNVs encompassing NUP188 span also other proximal genes. There are no relevant SNVs.

The gene is part of the ID panel of VCGS (TGW024_genelist_V3 - Oct2018) which was also listed as source in the current panel.

Overall, red rating (or removal from the current panel) seems appropriate.
Created: 24 Sep 2019, 4:40 p.m. | Last Modified: 24 Sep 2019, 4:40 p.m.
Panel Version: 2.1046


Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Victorian Clinical Genetics Services
  • Sandestig-Stefanova syndrome, 618804
Clinvar variants
Variants in NUP188
Panels with this gene

History Filter Activity

29 Sep 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: NUP188 were changed from to Sandestig-Stefanova syndrome, 618804

29 Sep 2020, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: NUP188 were set to

29 Sep 2020, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: NUP188 was changed from to BIALLELIC, autosomal or pseudoautosomal

29 Sep 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: nup188 has been classified as Amber List (Moderate Evidence).

29 Sep 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: NUP188 was added gene: NUP188 was added to Intellectual disability. Sources: Victorian Clinical Genetics Services Mode of inheritance for gene: NUP188 was set to