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Intellectual disability

Gene: HNRNPK

Green List (high evidence)

HNRNPK (heterogeneous nuclear ribonucleoprotein K)
EnsemblGeneIds (GRCh38): ENSG00000165119
EnsemblGeneIds (GRCh37): ENSG00000165119
OMIM: 600712, Gene2Phenotype
HNRNPK is in 8 panels

3 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Please also note high number of likely pathogenic and pathogenic variants reported in this gene by clinical laboratories in ClinVar
Created: 18 Jun 2018, 1:52 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changed from Amber to Green, there is now enough evidence to support gene-disease association.
Created: 9 Aug 2018, 12:09 p.m.
in view of external clinical review this gene was reviewed again. The pathogenic variants listed in ClinVar were submitted by Clinical Genetics Research Group, University of Calgary and relates to the recently published paper by Au PYB et al,. (2018) PMID: 29904177 who reported 6 additional cases with Au-Kline syndrome (AKS). These additional patients also demonstrated that AKS does have a distinct facial gestalt and phenotype that can be differentiated from Kabuki syndrome (KS).Kline syndrome (AKS, OMIM 616580) is a multiple malformation syndrome, first reported in 2015, associated with intellectual disability. There are now a total of 9 patients with de novo loss-of-function variants in HNRNPK, one individual with a de novo missense variant in addition to 3 patients with de novo deletions of 9q21.32 that encompass HNRNPK.
Created: 9 Aug 2018, 12:06 p.m.
Comment on publications: Added recent publication to support green rating. Au PYB et al,. (2018) PMID: 29904177 reported 6 additional cases with Au-Kline syndrome
Created: 9 Aug 2018, 11:38 a.m.
Comment on mode of inheritance: updated MOI as suggested by expert review and publication
Created: 9 Aug 2018, 11:31 a.m.
After review with the clinical team about the clinical overlap with Au-Kline syndrome and Kabuki syndrome it was decided not to add this gene to the Kabuki syndrome panel. Only with further cases we will get a better idea of the phenotypic spectrum aside from ID.
Created: 18 Dec 2017, 4:23 p.m.
HNRNPK haploinsufficiency causes Au-Kline syndrome which presents with psychomotor developmental delay, intellectual disability, characteristic face, cardiac, urogenital, skeletal abnormalities, and hypotonia. To date only two unrelated cases have been reported. Also it is thought there is clinical overlap with Kabuki syndrome PMID: 26954065,28771707,28374925.
Created: 18 Dec 2017, 3:36 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Au-Kline syndrome, 616580

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: This gene was sourced from the ClinGen Gene Validity Classification Summary. Determined as MODERATE by calculated classification and MODERATE by Expert curation (dated 11/15/2016). Available here: https://search.clinicalgenome.org/kb/gene-validity/5456. Comments provided by the expert curation: Evidence is rapidly emerging supporting the association between HNRNPK and Au-Kline syndrome. Gallardo et al. published a paper in 2015 describing an Hnrnpk +/- haploinsufficient mouse, which they developed to study its role in tumorigenesis. Personal communication with the senior author of that paper, Sean Post, in August 2016, revealed that the haploinsufficient mice appeared to have "significant reduction in overall size and had numerous structural/bone abnormalities," remniscient of the human phenotype, though he clarified that his group is not able to formally assess them for these types of phenotypes. Additionally, we are aware of at least one additional unpublished case - this evidence is not being formally considered, as it is not part of the public domain.
Created: 4 Jul 2017, 2:39 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation; OMIM:616580; Orphanet:453499

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Other
Phenotypes
  • Au-Kline syndrome, 616580
  • intellectual disability
OMIM
600712
Clinvar variants
Variants in HNRNPK
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to HNRNPK.

9 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

9 Aug 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: HNRNPK were set to 26173930; 26954065; 28771707; 26638989; 28374925; 29904177

9 Aug 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: HNRNPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

9 Aug 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: HNRNPK were set to 26173930; 26954065; 28771707; 26638989; 28374925

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

8 Jan 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for HNRNPK were set to 26173930; 26954065; 28771707; 26638989

5 Jan 2018, Gel status: 2

Set mode of inheritance, Set publications

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene HNRNPK was set to ['26173930', ' 26954065', '28771707 ']

4 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

4 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

4 Jul 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

HNRNPK was added to Intellectual disabilitypanel. Sources: Other

4 Jul 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

HNRNPK was created by ellenmcdonagh