Dicarboxylic aminoaciduria

Summary

Dicarboxylic aminoaciduria (MONDO:0009110) is a disease caused by SLC1A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Specific population) [Orphanet-validated]
• Causal gene: SLC1A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 117

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	2.76	Specific population	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	dicarboxylic aminoaciduria
Mondo ID	MONDO:0009110
MeSH	C536171
OMIM	222730
Orphanet	2195
DOID	DOID:0060650
ICD-11	1947265216
SNOMED CT	716747007
UMLS	C1857253
MedGen	387782
GARD	0001855
Is cancer (heuristic)	no

Also known as: DCBXA · dicarboxylic aminoaciduria · Dicarboxylicaminoaciduria · glutamate-aspartate transport defect

Data availability: 117 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 › dicarboxylic aminoaciduria

Related subtypes (18): blue diaper syndrome, ocular cystinosis, juvenile nephropathic cystinosis, cystinuria, hyperdibasic aminoaciduria type 1, lysinuric protein intolerance, Hartnup disease, histidinuria due to a renal tubular defect, iminoglycinuria, oculocerebrorenal syndrome, hypotonia-cystinuria syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, episodic ataxia type 6, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, disorder of neutral amino acid transport, autosomal recessive cerebellar ataxia - pyramidal signs - nystagmus - oculomotor apraxia syndrome, nephropathic infantile cystinosis, undetermined early-onset epileptic encephalopathy

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

117 retrieved; paginated sample, class counts are floors:

82 uncertain significance, 18 benign, 9 likely benign, 5 conflicting classifications of pathogenicity, 3 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
367037	NM_004170.6(SLC1A1):c.123C>T (p.His41=)	SLC1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367041	NM_004170.6(SLC1A1):c.311T>C (p.Ile104Thr)	SLC1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367047	NM_004170.6(SLC1A1):c.633C>T (p.Asn211=)	SLC1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367056	NM_004170.6(SLC1A1):c.1227T>C (p.Ala409=)	SLC1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
713810	NM_004170.6(SLC1A1):c.1200G>A (p.Thr400=)	SLC1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367029	NM_004170.6(SLC1A1):c.-185G>C	LOC130001482	Uncertain significance	criteria provided, single submitter
367032	NM_004170.6(SLC1A1):c.-86G>C	LOC130001482	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034055	NM_004170.6(SLC1A1):c.768-4C>G	SLC1A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
155859	NM_004170.6(SLC1A1):c.1333C>T (p.Arg445Trp)	SLC1A1	no classifications from unflagged records	no classifications from unflagged records
155860	NM_004170.6(SLC1A1):c.1181TCA[1] (p.Ile395del)	SLC1A1	no classifications from unflagged records	no classifications from unflagged records
3065478	NM_004170.6(SLC1A1):c.484-2A>G	SLC1A1	no classifications from unflagged records	no classifications from unflagged records
367036	NM_004170.6(SLC1A1):c.120A>G (p.Glu40=)	SLC1A1	Uncertain significance	criteria provided, single submitter
367044	NM_004170.6(SLC1A1):c.441-5A>C	SLC1A1	Uncertain significance	criteria provided, single submitter
367045	NM_004170.6(SLC1A1):c.520G>A (p.Asp174Asn)	SLC1A1	Uncertain significance	criteria provided, single submitter
367048	NM_004170.6(SLC1A1):c.812T>C (p.Ile271Thr)	SLC1A1	Uncertain significance	criteria provided, single submitter
367050	NM_004170.6(SLC1A1):c.893T>C (p.Ile298Thr)	SLC1A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
367051	NM_004170.6(SLC1A1):c.1087G>A (p.Ala363Thr)	SLC1A1	Uncertain significance	criteria provided, single submitter
367053	NM_004170.6(SLC1A1):c.1150T>C (p.Leu384=)	SLC1A1	Uncertain significance	criteria provided, single submitter
367055	NM_004170.6(SLC1A1):c.1194-10G>A	SLC1A1	Uncertain significance	criteria provided, single submitter
367057	NM_004170.6(SLC1A1):c.1231G>A (p.Val411Met)	SLC1A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
367058	NM_004170.6(SLC1A1):c.1254C>G (p.Thr418=)	SLC1A1	Uncertain significance	criteria provided, single submitter
367059	NM_004170.6(SLC1A1):c.1398C>T (p.Ser466=)	SLC1A1	Uncertain significance	criteria provided, single submitter
367060	NM_004170.6(SLC1A1):c.1483G>A (p.Glu495Lys)	SLC1A1	Uncertain significance	criteria provided, single submitter
367061	NM_004170.6(SLC1A1):c.1521C>A (p.Gly507=)	SLC1A1	Uncertain significance	criteria provided, single submitter
367062	NM_004170.6(SLC1A1):c.*2G>A	SLC1A1	Uncertain significance	criteria provided, single submitter
367063	NM_004170.6(SLC1A1):c.*43C>T	SLC1A1	Uncertain significance	criteria provided, single submitter
367064	NM_004170.6(SLC1A1):c.*111G>T	SLC1A1	Uncertain significance	criteria provided, single submitter
367065	NM_004170.6(SLC1A1):c.*161G>A	SLC1A1	Uncertain significance	criteria provided, single submitter
367066	NM_004170.6(SLC1A1):c.*355A>T	SLC1A1	Uncertain significance	criteria provided, single submitter
367068	NM_004170.6(SLC1A1):c.*425T>C	SLC1A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

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	Strong	Autosomal recessive	dicarboxylic aminoaciduria	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,clinvar

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.