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Intellectual disability

Gene: KCNN3

Amber List (moderate evidence)

KCNN3 (potassium calcium-activated channel subfamily N member 3)
EnsemblGeneIds (GRCh38): ENSG00000143603
EnsemblGeneIds (GRCh37): ENSG00000143603
OMIM: 602983, Gene2Phenotype
KCNN3 is in 4 panels

3 reviews

Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Green List (high evidence)

Gripp et al 2021 reported three additional patients with gain-of-function KCNN3 variants (two de novo and one not known- father not tested, not maternal): NM_002249.6 c.1663G > T p.(Val555Phe), c.1616_1618del p.(Val539del) and c.859G > T p.(Ala287Ser). The authors noted the overlap in the phenotype due to KCNN3, KCNH1 and KCNK4 variants with moderate developmental delay or mild-to-moderate intellectual disability, coarse facial features, gingival enlargement, distal digital hypoplasia and hypertrichosis and proposed to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance.
Created: 20 Feb 2021, 5:48 p.m. | Last Modified: 20 Feb 2021, 5:48 p.m.
Panel Version: 3.963

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
developmental delay; ID; hypotonia; gingival enlargement; hypertrichosis; nail anomalies

Publications

Mode of pathogenicity
Other

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

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Now at least 6 unrelated individuals with different gain-of-function KCNN3 variants (PMIDs: 31155282 and 33594261). Phenotypes include mild-to-moderate DD and/or ID.
Created: 1 Mar 2021, 11:10 a.m. | Last Modified: 1 Mar 2021, 11:10 a.m.
Panel Version: 3.966
Comment on mode of pathogenicity: Gain-of-function variants identified in all patients reported to date.
Created: 24 Jul 2020, 12:17 p.m. | Last Modified: 26 Feb 2021, 12:31 p.m.
Panel Version: 3.966
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - three unrelated cases with relevant phenotype, although future re-evaluation of the two younger patients may be useful.
Created: 24 Jul 2020, 12:12 p.m. | Last Modified: 24 Jul 2020, 12:12 p.m.
Panel Version: 3.192
Associated with phenotype in OMIM, and probable gene-disease association in G2P.

Bauer et al. (2019) PMID: 31155282 - De novo heterozygous gain-of-function variants identified in three unrelated individuals with ZimmermannLaband syndrome. Mild-moderate ID was reported in a 46-year-old man, while developmental delay was noted for the other two patients: a 4.5-year-old (first words at 2.5 y; attends nursery) and 5.5-year-old girl (limited spoken language; attends school with a personal aide). Additional features include coarse face, gingival hyperplasia, and/or nail hypo- or aplasia.
Created: 24 Jul 2020, 11:08 a.m. | Last Modified: 24 Jul 2020, 12:04 p.m.
Panel Version: 3.191

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

Phenotypes
Zimmermann-Laband syndrome 3, 618658

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three unrelated individuals reported.
Sources: Expert list
Created: 8 Feb 2020, 9:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Zimmermann-Laband syndrome 3; OMIM# 618658

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Zimmermann-Laband syndrome 3, OMIM:618658
Tags
for-review
OMIM
602983
Clinvar variants
Variants in KCNN3
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

1 Mar 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: KCNN3 were set to 31155282

26 Feb 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3, OMIM:618658

24 Jul 2020, Gel status: 2

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: KCNN3 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

24 Jul 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: kcnn3 has been classified as Amber List (Moderate Evidence).

24 Jul 2020, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: KCNN3.

8 Feb 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: KCNN3 was added gene: KCNN3 was added to Intellectual disability. Sources: Expert list Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNN3 were set to 31155282 Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3; OMIM# 618658 Review for gene: KCNN3 was set to GREEN gene: KCNN3 was marked as current diagnostic