Developmental and epileptic encephalopathy, 25

Summary

Developmental and epileptic encephalopathy, 25 (MONDO:0014392) is a disease caused by SLC13A5 (GenCC Definitive), with 3 cohort genes and 3 clinical trials.

At a glance

• Causal gene: SLC13A5 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 674
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 25
Mondo ID	MONDO:0014392
OMIM	615905
DOID	DOID:0080453
UMLS	C4014621
MedGen	863058
GARD	0012901
NORD	1914
Is cancer (heuristic)	no

Also known as: DEE25 · developmental and epileptic encephalopathy, 25 · early infantile epileptic encephalopathy 25 · early infantile epileptic encephalopathy caused by mutation in SLC13A5 · EIEE25 · epileptic encephalopathy, early infantile, 25 · epileptic encephalopathy, early infantile, type 25 · SLC13A5 Citrate Transporter Disorder · SLC13A5 deficiency · SLC13A5 early infantile epileptic encephalopathy

Data availability: 674 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 › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn disorder of amino acid transport › undetermined early-onset epileptic encephalopathy › developmental and epileptic encephalopathy, 25

Related subtypes (15): developmental and epileptic encephalopathy, 13, developmental and epileptic encephalopathy, 21, developmental and epileptic encephalopathy, 24, developmental and epileptic encephalopathy, 26, developmental and epileptic encephalopathy, 28, developmental and epileptic encephalopathy, 29, developmental and epileptic encephalopathy, 31A, developmental and epileptic encephalopathy, 32, developmental and epileptic encephalopathy, 33, developmental and epileptic encephalopathy, 41, developmental and epileptic encephalopathy, 42, developmental and epileptic encephalopathy, 44, developmental and epileptic encephalopathy, 45, developmental and epileptic encephalopathy, 46, developmental and epileptic encephalopathy, 47

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

600 retrieved; paginated sample, class counts are floors:

303 likely benign, 201 uncertain significance, 28 pathogenic, 19 conflicting classifications of pathogenicity, 19 likely pathogenic, 12 benign, 11 benign/likely benign, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070161	NC_000017.10:g.(?6616531)(6616672_?)del	SLC13A5	Pathogenic	criteria provided, single submitter
1352224	NM_177550.5(SLC13A5):c.1056-1G>C	SLC13A5	Pathogenic	criteria provided, single submitter
1402016	NM_177550.5(SLC13A5):c.1475del (p.Leu492fs)	SLC13A5	Pathogenic	criteria provided, single submitter
140752	NM_177550.5(SLC13A5):c.655G>A (p.Gly219Arg)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140753	NM_177550.5(SLC13A5):c.680C>T (p.Thr227Met)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455896	NM_177550.5(SLC13A5):c.1117C>T (p.Gln373Ter)	SLC13A5	Pathogenic	criteria provided, single submitter
1956988	NM_177550.5(SLC13A5):c.1412del (p.Leu471fs)	SLC13A5	Pathogenic	criteria provided, single submitter
2030414	NM_177550.5(SLC13A5):c.414G>A (p.Trp138Ter)	SLC13A5	Pathogenic	criteria provided, single submitter
2071759	NM_177550.5(SLC13A5):c.758G>A (p.Trp253Ter)	SLC13A5	Pathogenic	criteria provided, single submitter
2101634	NM_177550.5(SLC13A5):c.85_101delinsT (p.Ile29fs)	SLC13A5	Pathogenic	criteria provided, single submitter
218170	NM_177550.5(SLC13A5):c.1280C>T (p.Ser427Leu)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218171	NM_177550.5(SLC13A5):c.1022G>A (p.Trp341Ter)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218172	NM_177550.5(SLC13A5):c.1207_1217dup (p.Pro407fs)	SLC13A5	Pathogenic	criteria provided, single submitter
218173	NM_177550.5(SLC13A5):c.425C>T (p.Thr142Met)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218174	NM_177550.5(SLC13A5):c.1570G>C (p.Asp524His)	SLC13A5	Pathogenic	no assertion criteria provided
2427555	NC_000017.10:g.(?6607177)(6607395_?)del	SLC13A5	Pathogenic	criteria provided, single submitter
2579197	GRCh38/hg38 17p13.1(chr17:6690682-6696039)x0	SLC13A5	Pathogenic	criteria provided, single submitter
2707561	NM_177550.5(SLC13A5):c.1096del (p.Leu366fs)	SLC13A5	Pathogenic	criteria provided, single submitter
2760744	NM_177550.5(SLC13A5):c.15_19del (p.Ser6fs)	SLC13A5	Pathogenic	criteria provided, single submitter
2802014	NM_177550.5(SLC13A5):c.646del (p.Ala216fs)	SLC13A5	Pathogenic	criteria provided, single submitter
280534	NM_177550.5(SLC13A5):c.997C>T (p.Arg333Ter)	SLC13A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2983161	NM_177550.5(SLC13A5):c.812G>A (p.Trp271Ter)	SLC13A5	Pathogenic	criteria provided, single submitter
3243104	NC_000017.10:g.(?6609941)(6616652_?)del	SLC13A5	Pathogenic	criteria provided, single submitter
3243105	NC_000017.10:g.(?6607177)(6610495_?)del	SLC13A5	Pathogenic	criteria provided, single submitter
3256119	Single allele	SLC13A5	Pathogenic	criteria provided, single submitter
3639979	NM_177550.5(SLC13A5):c.395_396del (p.Thr132fs)	SLC13A5	Pathogenic	criteria provided, single submitter
3641048	NM_177550.5(SLC13A5):c.1354_1358dup (p.Leu454fs)	SLC13A5	Pathogenic	criteria provided, single submitter
3664328	NM_177550.5(SLC13A5):c.806G>A (p.Trp269Ter)	SLC13A5	Pathogenic	criteria provided, single submitter
4715028	NM_177550.5(SLC13A5):c.1118del (p.Gln373fs)	SLC13A5	Pathogenic	criteria provided, single submitter
4715742	NM_177550.5(SLC13A5):c.238_239del (p.Val80fs)	SLC13A5	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · 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
SLC13A5	Definitive	Autosomal recessive	developmental and epileptic encephalopathy, 25	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC13A5	Orphanet:1946	Amelocerebrohypohidrotic syndrome
SLC13A5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
AIPL1	Orphanet:1872	Cone rod dystrophy
AIPL1	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC13A5	HGNC:23089	ENSG00000141485	Q86YT5	Na(+)/citrate cotransporter	gencc,clinvar
TXNDC17	HGNC:28218	ENSG00000129235	Q9BRA2	Thioredoxin domain-containing protein 17	clinvar
AIPL1	HGNC:359	ENSG00000129221	Q9NZN9	Aryl-hydrocarbon-interacting protein-like 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC13A5	Na(+)/citrate cotransporter	High-affinity sodium/citrate cotransporter that mediates the entry of citrate into cells, which is a critical participant of biochemical pathways.
TXNDC17	Thioredoxin domain-containing protein 17	Disulfide reductase.
AIPL1	Aryl-hydrocarbon-interacting protein-like 1	May be important in protein trafficking and/or protein folding and stabilization.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC13A5	Other/Unknown	no		SLC13A/DASS, Na/sul_symport_CS
TXNDC17	Enzyme (other)	yes	1.8.1.6	TXNDC17_dom, Thioredoxin-like_sf, TXNDC17-like
AIPL1	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pancreatic ductal cell	2
liver	1
parotid gland	1
right lobe of liver	1
esophagus mucosa	1
lower esophagus mucosa	1
buccal mucosa cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC13A5	148	broad	yes	right lobe of liver, liver, parotid gland
TXNDC17	255	ubiquitous	marker	pancreatic ductal cell, lower esophagus mucosa, esophagus mucosa
AIPL1	62	tissue_specific	marker	buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC13A5	1,574
TXNDC17	1,013
AIPL1	891

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIPL1	Q9NZN9	6
SLC13A5	Q86YT5	4
TXNDC17	Q9BRA2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLC-mediated transport of organic anions	1	3806.7×	0.001	SLC13A5
Sodium-coupled sulphate, di- and tri-carboxylate transporters	1	2284.0×	0.001	SLC13A5
R-HSA-425366	1	181.3×	0.009	SLC13A5
SLC-mediated transmembrane transport	1	59.2×	0.021	SLC13A5
Transport of small molecules	1	25.1×	0.040	SLC13A5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
succinate transport	1	5617.3×	0.002	SLC13A5
oxaloacetate transport	1	2808.7×	0.002	SLC13A5
fumarate transport	1	2808.7×	0.002	SLC13A5
citrate transport	1	1872.4×	0.002	SLC13A5
protein farnesylation	1	1872.4×	0.002	AIPL1
alpha-ketoglutarate transport	1	1404.3×	0.002	SLC13A5
regulation of opsin-mediated signaling pathway	1	561.7×	0.004	AIPL1
phototransduction, visible light	1	432.1×	0.004	AIPL1
retina homeostasis	1	374.5×	0.004	AIPL1
cellular response to lithium ion	1	374.5×	0.004	SLC13A5
tumor necrosis factor-mediated signaling pathway	1	110.1×	0.012	TXNDC17
transmembrane transport	1	56.2×	0.022	SLC13A5
visual perception	1	26.5×	0.043	AIPL1
negative regulation of apoptotic process	1	11.6×	0.090	AIPL1
apoptotic process	1	9.6×	0.101	AIPL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC13A5	0	0
TXNDC17	0	0
AIPL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SLC13A5	14	Binding:11, Functional:3
TXNDC17	3	Binding:3
AIPL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TXNDC17	1.8.1.6	cystine reductase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	TXNDC17
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SLC13A5, AIPL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC13A5	14	—
TXNDC17	3	—
AIPL1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07102524	PHASE1/PHASE2	NOT_YET_RECRUITING	Intrathecal Gene Therapy For SLC13A5 Citrate Transporter Disorder
NCT04681781	Not specified	ENROLLING_BY_INVITATION	SLC13A5 Deficiency Natural History Study - Remote Only
NCT06144957	Not specified	ENROLLING_BY_INVITATION	SLC13A5 Deficiency Natural History Study - United States Only