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Intellectual disability

Gene: DEPDC5

Green List (high evidence)
DEPDC5 (DEP domain containing 5)
EnsemblGeneIds (GRCh38): ENSG00000100150
EnsemblGeneIds (GRCh37): ENSG00000100150
OMIM: 614191, Gene2Phenotype
DEPDC5 is in 5 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Phenotypes updated on 1st Sept 2026.
Created: 1 Sep 2026, 2:18 p.m. | Last Modified: 1 Sep 2026, 2:18 p.m.
Panel Version: 11.28
Comment on mode of inheritance: Based on large literature reviews, intellectual disability is present in only 12-28% of individuals with monoallelic DEPDC5 variants. In addition, the ID severity is usually mild, and uniformly diagnosed in patients with existing epilepsy - likely secondary to seizures. Epilepsy is the presenting feature, reported in all patients with DEPDC5 variants, and this gene is already Green on Early onset or syndromic epilepsy.
In patients with biallelic DEPDC5 variants, developmental delay is more severe, and was the presenting feature in several cases (PMID:36067010). Hence, the MOI should be changed from 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' to 'BIALLELIC, autosomal or pseudoautosomal' on this panel. As this is a demotion for monoallelic cases, an 'expert-review' tag is added to ensure NHSE agreement.
Created: 1 Sep 2026, 2:15 p.m. | Last Modified: 1 Sep 2026, 2:32 p.m.
Panel Version: 11.28
https://www.ncbi.nlm.nih.gov/books/NBK385626/ - DEPDC5-Related Epilepsy entry on GeneReviews (Baulac & Baldassari, updated in 2023) states that 100% of individuals with DEPDC5-related disease present with epilepsy (most commonly frontal lobe seizures / sleep-related hypermotor epilepsy). Meanwhile, neurodevelopment and behaviour is normal in most reported cases. Intellectual disability was present in only 12% of individuals, and likely secondary to brain malfromations and infantile spasms.

PMID: 41118617 Ochoa-Urrea et al., 2025
Review of 170 families with DEPDC5-Related Epilepsy. 76.1% of variant carriers developed epilepsy by age 10 years. Cortical malformations were present in 28% of those with available MRI.
Early seizure onset strongly correlated with drug resistance (p = 2.4e-08), intellectual disability (p = 2.1e-08), and lesional MRI (p = 2.2e-08).
Intellectual disability, usually mild, was identified in 27% of affected individuals, and psychiatric comorbidities—such as attention deficits, oppositional behaviours, mood disorders, and autism—affected 46% of the studied cohort. ID was reported exclusively in individuals with existing epilepsy.
Created: 1 Sep 2026, 2:11 p.m. | Last Modified: 1 Sep 2026, 2:11 p.m.
Panel Version: 11.26
BIALLELIC CASES - review by Achchuthan Shanmugasundram (Genomics England Curator), copied from Early onset or syndromic epilepsy panel:

The association of monoallelic variants in DEPDC5 gene to familial focal epilepsy (MIM #604364) have already been established with previous reviews and the existence of this phenotype in both OMIM and Gene2Phenotype.

PMID:32848577 reported a child with a homozygous missense variant (p.Pro1031His) who presented with cortical dysplasia and childhood onset epilepsy.

PMID:36067010 reported homozygous missense variants in five unrelated families (three Irish Traveller families with same variant - p.Thr337Arg; and one Tunisian and one Lebanese families with the same variant - p.Arg806Cys). All nine children from these five families presented with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe psychomotor developmental delay. Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. The disease mechanism is suggested as 'loss of function' as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

DEPDC5 is now associated with AR Developmental and epileptic encephalopathy 111, OMIM:620504, as well as AD Epilepsy, familial focal, with variable foci 1, OMIM:604364 (OMIM accessed 1st Sept 2026).
Created: 1 Sep 2026, 1:54 p.m. | Last Modified: 1 Sep 2026, 1:59 p.m.
Panel Version: 11.26

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, familial focal, with variable foci 1, OMIM:604364; epilepsy, familial focal, with variable foci 1, MONDO:0024556; Developmental and epileptic encephalopathy 111, OMIM:620504; developmental and epileptic encephalopathy 111, MONDO:0957780

Publications

Created: 1 Sep 2026, 1:54 p.m.
Last Modified: 1 Sep 2026, 2:32 p.m.
Panel version: 11.28

Caroline Wright (Sanger)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI (FFEVF)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_omim_20150205_epilepsies . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 5:31 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; omim_20150205_epilepsies; sfari_20150206; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:17 p.m.

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

Publications

Created: 2 Aug 2017, 4:46 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

I don't know

Created: 23 Feb 2016, 10:16 a.m.

Panel version: 0.306

Richard Scott (Genomics England Curator)

Comment when marking as ready: Confirmed DD gene; includes ID in some
Created: 7 Feb 2016, 7:07 a.m.
Created: 7 Feb 2016, 7:07 a.m.

Panel version: 0.98

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Epilepsy, familial focal, with variable foci 1, OMIM:604364
  • epilepsy, familial focal, with variable foci 1, MONDO:0024556
  • Developmental and epileptic encephalopathy 111, OMIM:620504
  • developmental and epileptic encephalopathy 111, MONDO:0957780
Tags
Q3_26_expert_review Q3_26_MOI
OMIM
614191
Clinvar variants
Variants in DEPDC5
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 Sep 2026, Gel status: 3

Removed Tag, Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_demote_red was removed from gene: DEPDC5. Tag Q3_26_MOI tag was added to gene: DEPDC5.

1 Sep 2026, Gel status: 3

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1, OMIM:604364 to Epilepsy, familial focal, with variable foci 1, OMIM:604364; epilepsy, familial focal, with variable foci 1, MONDO:0024556; Developmental and epileptic encephalopathy 111, OMIM:620504; developmental and epileptic encephalopathy 111, MONDO:0957780

1 Sep 2026, Gel status: 3

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: DEPDC5 were set to 14510823; 15329069; 10825362; 10577924; 9851433; 23542701

1 Sep 2026, Gel status: 3

Added Tag, Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_expert_review tag was added to gene: DEPDC5. Tag Q3_26_demote_red tag was added to gene: DEPDC5.

8 Sep 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: DEPDC5 were changed from FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI (FFEVF) to Epilepsy, familial focal, with variable foci 1, OMIM:604364

12 Mar 2018, Gel status: 3

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.

7 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

7 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

DEPDC5 was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

DEPDC5 was added to Intellectual disabilitypanel. Sources: Expert Review Amber