Hot water reflex epilepsy

Summary

Hot water reflex epilepsy (MONDO:0013229) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	4	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hot water reflex epilepsy
Mondo ID	MONDO:0013229
OMIM	613339
Orphanet	166412
DOID	DOID:0081104
SNOMED CT	230454005
UMLS	C4706506
MedGen	1631373
GARD	0017028
Is cancer (heuristic)	no

Also known as: epilepsy, hot water · hot water epilepsy

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › reflex epilepsy › inherited reflex epilepsy › hot water reflex epilepsy

Related subtypes (1): photosensitive epilepsy

Subtypes (2): epilepsy, hot water, 2, epilepsy, hot water, 1

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
SLC1A1	Supportive	Autosomal dominant	hot water reflex epilepsy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC1A1	Orphanet:166412	Hot water reflex epilepsy
SLC1A1	Orphanet:2195	Dicarboxylic aminoaciduria

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC1A1	HGNC:10939	ENSG00000106688	P43005	Excitatory amino acid transporter 3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC1A1	Excitatory amino acid transporter 3	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC1A1	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
ileal mucosa	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC1A1	248	ubiquitous	marker	corpus epididymis, jejunal mucosa, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC1A1	2,309

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC1A1	P43005	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 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
Defective SLC1A1 is implicated in schizophrenia 18 (SCZD18) and dicarboxylic aminoaciduria (DCBXA)	1	11420.0×	3e-04	SLC1A1
SLC-mediated transport of amino acids	1	2284.0×	7e-04	SLC1A1
Glutamate Neurotransmitter Release Cycle	1	456.8×	0.002	SLC1A1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
D-aspartate transmembrane transport	1	16852.0×	0.001	SLC1A1
regulation of protein targeting to membrane	1	16852.0×	0.001	SLC1A1
neurotransmitter receptor transport to plasma membrane	1	16852.0×	0.001	SLC1A1
response to decreased oxygen levels	1	8426.0×	0.001	SLC1A1
L-aspartate transmembrane transport	1	8426.0×	0.001	SLC1A1
L-cysteine transport	1	5617.3×	0.001	SLC1A1
cellular response to mercury ion	1	5617.3×	0.001	SLC1A1
D-aspartate import across plasma membrane	1	3370.4×	0.001	SLC1A1
cellular response to ammonium ion	1	3370.4×	0.001	SLC1A1
cellular response to bisphenol A	1	3370.4×	0.001	SLC1A1
L-glutamate import	1	2808.7×	0.001	SLC1A1
response to anesthetic	1	2808.7×	0.001	SLC1A1
intracellular glutamate homeostasis	1	2808.7×	0.001	SLC1A1
L-aspartate import across plasma membrane	1	2808.7×	0.001	SLC1A1
G protein-coupled dopamine receptor signaling pathway	1	1872.4×	0.002	SLC1A1
righting reflex	1	1872.4×	0.002	SLC1A1
L-glutamate import across plasma membrane	1	1872.4×	0.002	SLC1A1
conditioned place preference	1	1685.2×	0.002	SLC1A1
glutathione biosynthetic process	1	1532.0×	0.002	SLC1A1
cellular response to cocaine	1	1296.3×	0.002	SLC1A1
response to morphine	1	1203.7×	0.002	SLC1A1
transepithelial transport	1	1203.7×	0.002	SLC1A1
grooming behavior	1	1123.5×	0.002	SLC1A1
motor neuron apoptotic process	1	1123.5×	0.002	SLC1A1
superoxide metabolic process	1	991.3×	0.002	SLC1A1
dopamine metabolic process	1	991.3×	0.002	SLC1A1
glutamate receptor signaling pathway	1	936.2×	0.002	SLC1A1
L-glutamate transmembrane transport	1	802.5×	0.002	SLC1A1
blood vessel morphogenesis	1	802.5×	0.002	SLC1A1
heart contraction	1	766.0×	0.002	SLC1A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
SLC1A1	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASPARTIC ACID	3	SLC1A1
GLUTAMIC ACID	3	SLC1A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC1A1	50	Binding:43, Functional:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
ASPARTIC ACID	3	SLC1A1
GLUTAMIC ACID	3	SLC1A1

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	1	SLC1A1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.