Intellectual disability
Gene: DPP6

DPP6 (dipeptidyl peptidase like 6)
EnsemblGeneIds (GRCh38): ENSG00000130226
EnsemblGeneIds (GRCh37): ENSG00000130226
OMIM: 126141, Gene2Phenotype
DPP6 is in 3 panels

4 reviews

Sarah Leigh (Genomics England Curator)

I don't know

DPP6 variants have been associated with Intellectual developmental disorder, autosomal dominant 33 in OMIM (#: 616311), but not with a phenotype in Gen2Phen. To date two monoallelic variants have been associated with OMIM: 616311 in two unrelated families, where the affected individuals all had microcephaly and intellectual disability (PMID:23832105). Various Dpp6 knock-down mouse models, showed that these mice had significantly lower body and brain weights in comparison to wildtype and displayed behaviours characteristic of reduced learning abilities and impaired memory (PMID: 21943606; 23832105; 29651237).
The ClinGen Gene-Disease Validity score for this gene is "Disputed" (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_3d41cebe-5490-419d-882d-4f3c6856be07-2021-05-05T160000.000Z) therefore, this gene will remain red.
Created: 29 Aug 2024, 2:55 p.m. | Last Modified: 29 Aug 2024, 3:43 p.m.

Panel Version: 7.20

The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Created: 3 May 2024, 11:55 a.m. | Last Modified: 3 May 2024, 11:55 a.m.

Panel Version: 6.11

Created: 3 May 2024, 11:55 a.m.
Last Modified: 29 Aug 2024, 3:43 p.m.
Panel version: 7.20

Ivone Leong (Genomics England Curator)

This gene has been tagged for GMS expert review.
Created: 7 Nov 2023, 2:28 p.m. | Last Modified: 7 Nov 2023, 2:28 p.m.

Panel Version: 5.335

Created: 7 Nov 2023, 2:28 p.m.
Last Modified: 7 Nov 2023, 2:28 p.m.
Panel version: 5.335

Gavin Ryan (West Midlands Regional Genetics Laboratory)

Red List (low evidence)

The association of this gene with disease is disputed by ClinGen and they have stated 'There is currently no scoreable genetic evidence to support the pathogenic role of DPP6 in autosomal dominant complex neurodevelopmental disorder.' - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_3d41cebe-5490-419d-882d-4f3c6856be07-2021-05-05T160000.000Z
Created: 3 Nov 2023, 11:37 a.m. | Last Modified: 3 Nov 2023, 11:37 a.m.

Panel Version: 5.332

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 3 Nov 2023, 11:37 a.m.
Last Modified: 3 Nov 2023, 11:37 a.m.
Panel version: 5.332

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Comment on list classification: Updated rating from Red to Green based on 3 unrelated cases described in PMID:23832105. 3 patients, 2 deletions and a missense.
Created: 3 Mar 2017, 1:26 p.m.

Added 'deletions' tag based on 2 deletions (336 kb and 362 kb) described in PMID:23832105.
Created: 3 Mar 2017, 1:25 p.m.

Comment on mode of inheritance: Mode of inheritance taken from PMID:23832105.
Created: 3 Mar 2017, 1:25 p.m.

PMID:23832105 (Liao et al., 2013) show that LOF variation in the DPP6 gene is associated with AD microcephaly and mental retardation. In 3 patients they identify 2 de novo deletions (336kb and 362kb in patients BY0712 and BY2018) and a missense variant (patient BY2950: M385L). Microcephaly plus moderate to severe mental retardation is noted in all 3 individuals (Table 1).
Created: 3 Mar 2017, 1:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311

Publications

23832105

Created: 3 Mar 2017, 1:25 p.m.

Panel version: 1.74

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Red
NHS GMS
Other

Phenotypes

Intellectual developmental disorder, autosomal dominant 33, OMIM:616311

Tags

deletions

OMIM

126141

Clinvar variants

Variants in DPP6

Penetrance

Complete

Publications

Panels with this gene