Intellectual disability
Gene: KCNN3

KCNN3 (potassium calcium-activated channel subfamily N member 3)
EnsemblGeneIds (GRCh38): ENSG00000143603
EnsemblGeneIds (GRCh37): ENSG00000143603
OMIM: 602983, Gene2Phenotype
KCNN3 is in 5 panels

4 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

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

33594261

Mode of pathogenicity
Other

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

Created: 20 Feb 2021, 5:48 p.m.
Last Modified: 20 Feb 2021, 5:48 p.m.
Panel version: 3.963

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

Created: 24 Jul 2020, 11:08 a.m.
Last Modified: 26 Feb 2021, 12:31 p.m.
Panel version: 3.966

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

31155282

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

Created: 8 Feb 2020, 9:32 a.m.

Panel version: 3.0

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green

Phenotypes

Zimmermann-Laband syndrome 3, OMIM:618658

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