acute neonatal citrullinemia type I

Summary

acute neonatal citrullinemia type I (MONDO:0016600) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acute neonatal citrullinemia type I
Mondo ID	MONDO:0016600
Orphanet	247546
UMLS	C5679618
MedGen	1843387
GARD	0020659
Is cancer (heuristic)	no

Also known as: acute neonatal citrullinemia type 1 · classic citrullinemia type 1 · classic citrullinemia type I

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: 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 › urea cycle disorder › citrullinemia › citrullinemia type I › acute neonatal citrullinemia type I

Related subtypes (1): adult-onset citrullinemia type I

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: 6 · 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
ASS1	Definitive	Autosomal recessive	citrullinemia type I	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASS1	Orphanet:247546	Acute neonatal citrullinemia type I
ASS1	Orphanet:247573	Late-onset citrullinemia type I

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
ASS1	HGNC:758	ENSG00000130707	P00966	Argininosuccinate synthase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASS1	Argininosuccinate synthase	One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ASS1	Enzyme (other)	yes	6.3.4.5	Arginosuc_synth, Rossmann-like_a/b/a_fold, Arginosuc_synth_CS

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
liver	1
palpebral conjunctiva	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASS1	292	ubiquitous	marker	right lobe of liver, palpebral conjunctiva, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASS1	3,101

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASS1	P00966	1

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
ASS1 variants cause citrullinemia	1	5710.0×	7e-04	ASS1
Urea cycle	1	878.5×	0.002	ASS1
Metabolism of amino acids and derivatives	1	67.6×	0.020	ASS1
Metabolism	1	11.6×	0.086	ASS1

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 argininosuccinate metabolic process	1	16852.0×	9e-04	ASS1
obsolete citrulline metabolic process	1	8426.0×	9e-04	ASS1
L-arginine biosynthetic process	1	5617.3×	9e-04	ASS1
response to mycotoxin	1	5617.3×	9e-04	ASS1
cellular response to oleic acid	1	5617.3×	9e-04	ASS1
cellular response to amine stimulus	1	5617.3×	9e-04	ASS1
cellular response to ammonium ion	1	3370.4×	0.001	ASS1
negative regulation of leukocyte cell-cell adhesion	1	2808.7×	0.001	ASS1
aspartate metabolic process	1	2106.5×	0.001	ASS1
midgut development	1	2106.5×	0.001	ASS1
cellular response to laminar fluid shear stress	1	2106.5×	0.001	ASS1
diaphragm development	1	1872.4×	0.001	ASS1
urea cycle	1	1296.3×	0.002	ASS1
response to growth hormone	1	1123.5×	0.002	ASS1
cellular response to glucagon stimulus	1	842.6×	0.002	ASS1
response to zinc ion	1	624.1×	0.003	ASS1
cellular response to dexamethasone stimulus	1	581.1×	0.003	ASS1
positive regulation of nitric oxide biosynthetic process	1	455.5×	0.004	ASS1
acute-phase response	1	421.3×	0.004	ASS1
cellular response to amino acid stimulus	1	306.4×	0.005	ASS1
response to nutrient	1	295.6×	0.005	ASS1
cellular response to cAMP	1	290.6×	0.005	ASS1
circadian rhythm	1	244.2×	0.005	ASS1
liver development	1	221.7×	0.006	ASS1
cellular response to type II interferon	1	208.1×	0.006	ASS1
response to estradiol	1	198.3×	0.006	ASS1
cellular response to tumor necrosis factor	1	163.6×	0.007	ASS1
kidney development	1	140.4×	0.008	ASS1
cellular response to lipopolysaccharide	1	98.0×	0.011	ASS1
response to xenobiotic stimulus	1	69.1×	0.014	ASS1

Therapeutics

Drug target analysis

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

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
ASS1	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
ASS1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASS1	6.3.4.5	argininosuccinate synthase

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	ASS1
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)
ASS1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.