Infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome

Summary

Infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome (MONDO:0016981) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 25

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002134	Abnormality of the basal ganglia	Very frequent (80-99%)
HP:0012697	Small basal ganglia	Very frequent (80-99%)
HP:0000711	Restlessness	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001289	Confusion	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002273	Tetraparesis	Frequent (30-79%)
HP:0002329	Drowsiness	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0007105	Infantile encephalopathy	Frequent (30-79%)
HP:0007185	Loss of consciousness	Frequent (30-79%)
HP:0012747	Abnormal brainstem MRI signal intensity	Frequent (30-79%)
HP:0030215	Inappropriate crying	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0002093	Respiratory insufficiency	Occasional (5-29%)
HP:0002133	Status epilepticus	Occasional (5-29%)
HP:0002510	Spastic tetraplegia	Occasional (5-29%)
HP:0004302	Functional motor deficit	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0012469	Infantile spasms	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome
Mondo ID	MONDO:0016981
Orphanet	263410
UMLS	C5190692
MedGen	1675231
GARD	0020899
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › disorder of metabolite absorption and transport › disorder of vitamin and non-protein cofactor absorption and transport › disorder of thiamine metabolism and transport › infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome

Related subtypes (1): thiamine-responsive dysfunction syndrome

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: 9 · Orphanet: 3 · 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
SLC19A3	Definitive	Autosomal recessive	biotin-responsive basal ganglia disease	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC19A3	Orphanet:199348	Thiamine-responsive encephalopathy
SLC19A3	Orphanet:263410	Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome
SLC19A3	Orphanet:65284	Biotin-thiamine-responsive basal ganglia disease

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
SLC19A3	HGNC:16266	ENSG00000135917	Q9BZV2	Thiamine transporter 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC19A3	Thiamine transporter 2	Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism.

Protein-family classification

Druggable: 1 · 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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC19A3	Transporter	yes		Folate_carrier, ThTr-2, MFS_trans_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
adipose tissue	1
adipose tissue of abdominal region	1
subcutaneous adipose tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC19A3	185	broad	marker	subcutaneous adipose tissue, adipose tissue, adipose tissue of abdominal region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC19A3	1,101

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC19A3	Q9BZV2	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Vitamin B1 (thiamin) metabolism	1	2284.0×	0.002	SLC19A3
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.011	SLC19A3
Metabolism of vitamins and cofactors	1	116.5×	0.011	SLC19A3
Metabolism	1	11.6×	0.086	SLC19A3

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
pyridoxine transport	1	5617.3×	3e-04	SLC19A3
thiamine-containing compound metabolic process	1	5617.3×	3e-04	SLC19A3
thiamine transport	1	4213.0×	3e-04	SLC19A3
thiamine transmembrane transport	1	4213.0×	3e-04	SLC19A3
thiamine diphosphate biosynthetic process	1	3370.4×	3e-04	SLC19A3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC19A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	SLC19A3
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)
SLC19A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.