Saccharopinuria

Summary

Saccharopinuria (MONDO:0010005) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 19

Clinical features

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0002161	Hyperlysinemia	Very frequent (80-99%)
HP:0011021	Abnormality of circulating enzyme level	Very frequent (80-99%)
HP:0001507	Growth abnormality	Frequent (30-79%)
HP:0003297	Hyperlysinuria	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0001264	Spastic diplegia	Occasional (5-29%)
HP:0001268	Mental deterioration	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001987	Hyperammonemia	Occasional (5-29%)
HP:0002066	Gait ataxia	Occasional (5-29%)
HP:0002936	Distal sensory impairment	Occasional (5-29%)
HP:0003131	Cystinuria	Occasional (5-29%)
HP:0011966	Elevated plasma citrulline	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0032397	Citrullinuria	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)
HP:0500151	Hypercystinemia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	saccharopinuria
Mondo ID	MONDO:0010005
MeSH	C537218
OMIM	268700
Orphanet	3124
SNOMED CT	111397004
UMLS	C0268556
MedGen	75693
GARD	0000314
Is cancer (heuristic)	no

Also known as: hyperlysinemia type II · saccharopine dehydrogenase deficiency · saccharopinuria

Data availability: 3 ClinVar variants.

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 lysine and hydroxylysine metabolism › saccharopinuria

Related subtypes (4): 2-aminoadipic 2-oxoadipic aciduria, seizures-intellectual disability due to hydroxylysinuria syndrome, hyperlysinemia, inborn disorder of lysine, hydroxylysine, and tryptophan metabolism

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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
252652	NM_005763.4(AASS):c.2762A>G (p.Gln921Arg)	AASS	Uncertain significance	criteria provided, multiple submitters, no conflicts
973452	NM_005763.4(AASS):c.1048G>A (p.Val350Met)	AASS	Uncertain significance	criteria provided, multiple submitters, no conflicts
973464	NM_005763.4(AASS):c.1876A>G (p.Ile626Val)	AASS	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AASS	Orphanet:2203	Hyperlysinemia
AASS	Orphanet:3124	Saccharopinuria

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
AASS	HGNC:17366	ENSG00000008311	Q9UDR5	Alpha-aminoadipic semialdehyde synthase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AASS	Alpha-aminoadipic semialdehyde synthase, mitochondrial	Bifunctional enzyme that catalyzes the first two steps in lysine degradation.

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)
AASS	Other/Unknown	no		Sacchrp_dh_NADP-bd, AlaDH/PNT_NAD(H)-bd, AlaDH/PNT_N

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
left ovary	1
mucosa of stomach	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AASS	260	ubiquitous	marker	mucosa of stomach, left ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AASS	1,333

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AASS	Q9UDR5	9

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
Lysine catabolism	1	1142.0×	0.003	AASS
Metabolism of amino acids and derivatives	1	67.6×	0.022	AASS
Metabolism	1	11.6×	0.086	AASS

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
obsolete L-lysine biosynthetic process via aminoadipic acid	1	8426.0×	4e-04	AASS
obsolete L-lysine catabolic process to acetyl-CoA via L-saccharopine	1	5617.3×	4e-04	AASS
obsolete lysine catabolic process	1	2407.4×	6e-04	AASS
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	AASS

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
AASS	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AASS

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)
AASS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.