Developmental and epileptic encephalopathy, 87

disease

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Also known as DEE87developmental and epileptic encephalopathy 87EIEE87EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 87

Summary

Developmental and epileptic encephalopathy, 87 (MONDO:0030059) is a disease caused by CDK19 (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: CDK19 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 87
Mondo ID	MONDO:0030059
OMIM	618916
DOID	DOID:0112221
UMLS	C5394501
MedGen	1719688
GARD	0016393
Is cancer (heuristic)	no

Also known as: DEE87 · developmental and epileptic encephalopathy 87 · EIEE87 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 87 · epileptic encephalopathy, early infantile, 87

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy, 87

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
973822	NM_015076.5(CDK19):c.82G>C (p.Gly28Arg)	AMD1	Pathogenic	criteria provided, single submitter
929848	NM_015076.5(CDK19):c.94T>C (p.Tyr32His)	CDK19	Pathogenic	criteria provided, single submitter
973853	NM_015076.5(CDK19):c.92C>A (p.Thr31Asn)	CDK19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
975815	NM_015076.5(CDK19):c.82G>A (p.Gly28Arg)	CDK19	Pathogenic	criteria provided, single submitter
975817	NM_015076.5(CDK19):c.589T>C (p.Phe197Leu)	CDK19	Likely pathogenic	no assertion criteria provided
975816	NM_015076.5(CDK19):c.95A>G (p.Tyr32Cys)	AMD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
929847	NM_015076.5(CDK19):c.586A>G (p.Thr196Ala)	CDK19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1696539	NM_015076.5(CDK19):c.457-3T>C	CDK19	Uncertain significance	criteria provided, single submitter
3235030	NM_015076.5(CDK19):c.1486T>A (p.Ser496Thr)	CDK19	Uncertain significance	criteria provided, single submitter
3237353	NM_015076.5(CDK19):c.1234G>T (p.Ala412Ser)	CDK19	Uncertain significance	criteria provided, single submitter
3770222	NM_015076.5(CDK19):c.1270C>T (p.Gln424Ter)	CDK19	Uncertain significance	criteria provided, single submitter
3896727	NM_015076.5(CDK19):c.264C>A (p.His88Gln)	CDK19	Uncertain significance	criteria provided, single submitter
3902060	NM_015076.5(CDK19):c.1218C>A (p.Asn406Lys)	CDK19	Uncertain significance	criteria provided, single submitter
3902061	NM_015076.5(CDK19):c.699T>G (p.Ile233Met)	CDK19	Uncertain significance	criteria provided, single submitter
4078238	NM_015076.5(CDK19):c.1042G>A (p.Gly348Ser)	CDK19	Uncertain significance	criteria provided, single submitter
4292578	NM_015076.5(CDK19):c.640G>A (p.Ala214Thr)	CDK19	Uncertain significance	criteria provided, single submitter
4532013	NM_015076.5(CDK19):c.968G>A (p.Arg323Lys)	CDK19	Uncertain significance	criteria provided, single submitter
975818	NM_015076.5(CDK19):c.594G>C (p.Trp198Cys)	CDK19	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805083	NM_015076.5(CDK19):c.410A>T (p.Asp137Val)	CDK19	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CDK19	Strong	Autosomal dominant	developmental and epileptic encephalopathy, 87	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDK19	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDK19	HGNC:19338	ENSG00000155111	Q9BWU1	Cyclin-dependent kinase 19	gencc,clinvar
AMD1	HGNC:457	ENSG00000123505	P17707	S-adenosylmethionine decarboxylase proenzyme	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMD1	S-adenosylmethionine decarboxylase proenzyme	Essential for biosynthesis of the polyamines spermidine and spermine.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDK19	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
AMD1	Enzyme (other)	yes	4.1.1.50	S-AdoMet_decarboxylase_euk, S-AdoMet_deCO2ase_core, S-AdoMet_deCO2ase_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	2
endothelial cell	1
medial globus pallidus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDK19	282	ubiquitous	marker	endothelial cell, medial globus pallidus, corpus callosum
AMD1	292	ubiquitous	marker	secondary oocyte, oocyte, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDK19	1,516
AMD1	173

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AMD1	P17707	28

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDK19	Q9BWU1	77.97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of polyamines	1	439.2×	0.030	AMD1
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.033	CDK19
RSV-host interactions	1	78.2×	0.033	CDK19
Adipogenesis	1	78.2×	0.033	CDK19
Regulation of lipid metabolism by PPARalpha	1	70.5×	0.033	CDK19
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.033	CDK19
PPARA activates gene expression	1	47.2×	0.039	CDK19
Metabolism of lipids	1	15.8×	0.092	CDK19
Viral Infection Pathways	1	15.4×	0.092	CDK19
Infectious disease	1	12.4×	0.103	CDK19
Developmental Biology	1	7.2×	0.158	CDK19
Disease	1	6.5×	0.159	CDK19
Metabolism	1	5.8×	0.165	CDK19

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
spermine biosynthetic process	1	4213.0×	6e-04	AMD1
spermidine biosynthetic process	1	4213.0×	6e-04	AMD1
polyamine metabolic process	1	1685.2×	1e-03	AMD1
cellular response to lipopolysaccharide	1	49.0×	0.025	CDK19
positive regulation of apoptotic process	1	28.4×	0.035	CDK19

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CDK19	SORAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK19	21	4
AMD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SORAFENIB	4	CDK19
QUIZARTINIB	4	CDK19
MIDOSTAURIN	4	CDK19
IMATINIB	4	CDK19
VATALANIB	3	CDK19
LINIFANIB	3	CDK19
ALVOCIDIB	3	CDK19
INDIRUBIN	2	CDK19
ISTISOCICLIB	2	CDK19
DORAMAPIMOD	2	CDK19
FORETINIB	2	CDK19
AT-7519	2	CDK19
CP-724714	2	CDK19
RAF-265	2	CDK19
TOZASERTIB	2	CDK19
SENEXIN B	1	CDK19
SEL-120 FREE BASE	1	CDK19
BMS-387032	1	CDK19
SEL-120	1	CDK19
SNS-314	1	CDK19
AST-487	1	CDK19

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CDK19	210	Binding:209, Functional:1
AMD1	39	Binding:39

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AMD1	4.1.1.50	adenosylmethionine decarboxylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CDK19	210

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

21 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
SORAFENIB	4	CDK19
QUIZARTINIB	4	CDK19
MIDOSTAURIN	4	CDK19
IMATINIB	4	CDK19
VATALANIB	3	CDK19
LINIFANIB	3	CDK19
ALVOCIDIB	3	CDK19
INDIRUBIN	2	CDK19
ISTISOCICLIB	2	CDK19
DORAMAPIMOD	2	CDK19
FORETINIB	2	CDK19
AT-7519	2	CDK19
CP-724714	2	CDK19
RAF-265	2	CDK19
TOZASERTIB	2	CDK19
SENEXIN B	1	CDK19
SEL-120 FREE BASE	1	CDK19
BMS-387032	1	CDK19
SEL-120	1	CDK19
SNS-314	1	CDK19
AST-487	1	CDK19

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CDK19
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	AMD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
AMD1	39	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: CDK19, AMD1