citrullinemia type II

Summary

citrullinemia type II (MONDO:0016603) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 88
• Phenotypes (HPO): 46
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

46 HPO clinical features (Orphanet curated; top 46 by frequency):

HPO ID	Term	Frequency
HP:0001397	Hepatic steatosis	Very frequent (80-99%)
HP:0008281	Acute hyperammonemia	Very frequent (80-99%)
HP:0011966	Elevated plasma citrulline	Very frequent (80-99%)
HP:0045082	Decreased body mass index	Very frequent (80-99%)
HP:0000711	Restlessness	Frequent (30-79%)
HP:0000718	Aggressive behavior	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0000738	Hallucinations	Frequent (30-79%)
HP:0000746	Delusion	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001289	Confusion	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002329	Drowsiness	Frequent (30-79%)
HP:0002354	Memory impairment	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003073	Hypoalbuminemia	Frequent (30-79%)
HP:0003075	Hypoproteinemia	Frequent (30-79%)
HP:0003077	Hyperlipidemia	Frequent (30-79%)
HP:0007159	Fluctuations in consciousness	Frequent (30-79%)
HP:0012164	Asterixis	Frequent (30-79%)
HP:0030166	Night sweats	Frequent (30-79%)
HP:0030765	Sleep terror	Frequent (30-79%)
HP:0031258	Delirium	Frequent (30-79%)
HP:0100738	Abnormal eating behavior	Frequent (30-79%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)
HP:0000805	Enuresis	Occasional (5-29%)
HP:0001259	Coma	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001395	Hepatic fibrosis	Occasional (5-29%)
HP:0001402	Hepatocellular carcinoma	Occasional (5-29%)
HP:0001733	Pancreatitis	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0002181	Cerebral edema	Occasional (5-29%)
HP:0002480	Hepatic encephalopathy	Occasional (5-29%)
HP:0003124	Hypercholesterolemia	Occasional (5-29%)
HP:0003233	Decreased HDL cholesterol concentration	Occasional (5-29%)
HP:0010529	Echolalia	Occasional (5-29%)
HP:0012569	Delayed menarche	Occasional (5-29%)
HP:0100754	Mania	Occasional (5-29%)
HP:0100785	Insomnia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	citrullinemia type II
Mondo ID	MONDO:0016603
Orphanet	247585
NCIT	C150603
SNOMED CT	716863007
UMLS	C1863844
MedGen	350276
GARD	0010215
Is cancer (heuristic)	no

Also known as: adult-onset citrin deficiency · adult-onset type 2 citrullinemia · adult-onset type II citrullinemia · citrullinemia type 2 · citrullinemia type II · CTLN2

Data availability: 88 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

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 › citrin deficiency › citrullinemia type II

Related subtypes (1): neonatal intrahepatic cholestasis due to citrin deficiency

Subtypes (1): citrullinemia, type II, adult-onset

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

88 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 24 conflicting classifications of pathogenicity, 9 pathogenic, 8 pathogenic/likely pathogenic, 4 likely pathogenic, 4 benign/likely benign, 3 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1451917	NM_014251.3(SLC25A13):c.1095del (p.Phe365fs)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
1451920	NM_014251.3(SLC25A13):c.754G>A (p.Glu252Lys)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21508	NM_014251.3(SLC25A13):c.1078C>T (p.Arg360Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21514	NM_014251.3(SLC25A13):c.1813C>T (p.Arg605Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21517	NM_014251.3(SLC25A13):c.615+5G>A	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
225472	NM_014251.3(SLC25A13):c.852_855del (p.Met285fs)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
2577099	NM_014251.3(SLC25A13):c.1622C>A (p.Ala541Asp)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3336478	NM_014251.3(SLC25A13):c.1793T>G (p.Leu598Arg)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
6002	NM_014251.3(SLC25A13):c.1177+1G>A	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
6003	NM_014251.3(SLC25A13):c.1638_1660dup (p.Ala554fs)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
6004	NM_014251.3(SLC25A13):c.674C>A (p.Ser225Ter)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
6005	NM_014251.3(SLC25A13):c.1311+1G>A	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
6006	NM_014251.3(SLC25A13):c.1799dup (p.Tyr600Ter)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813455	NM_014251.3(SLC25A13):c.1231G>A (p.Val411Met)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
850379	NM_014251.3(SLC25A13):c.848+3A>C	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
855835	NM_014251.3(SLC25A13):c.1048G>A (p.Asp350Asn)	SLC25A13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
92110	NM_014251.3(SLC25A13):c.1064G>A (p.Arg355Gln)	SLC25A13	Pathogenic	criteria provided, multiple submitters, no conflicts
1696310	NM_014251.3(SLC25A13):c.1210G>T (p.Glu404Ter)	SLC25A13	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2504051	NM_014251.3(SLC25A13):c.1307_1308delinsAA (p.Gly436Glu)	SLC25A13	Likely pathogenic	criteria provided, multiple submitters, no conflicts
417947	NM_014251.3(SLC25A13):c.468+1G>C	SLC25A13	Likely pathogenic	criteria provided, single submitter
934709	NM_014251.3(SLC25A13):c.1637C>T (p.Thr546Met)	SLC25A13	Likely pathogenic	criteria provided, multiple submitters, no conflicts
361027	NM_014251.3(SLC25A13):c.6G>T (p.Ala2=)	LOC129998833	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194403	NM_014251.3(SLC25A13):c.1434G>T (p.Gly478=)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
203938	NM_014251.3(SLC25A13):c.1910T>C (p.Val637Ala)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252921	NM_014251.3(SLC25A13):c.1505C>T (p.Pro502Leu)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2577098	NM_014251.3(SLC25A13):c.103A>G (p.Met35Val)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290076	NM_014251.3(SLC25A13):c.1680C>T (p.Ser560=)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361010	NM_014251.3(SLC25A13):c.1945G>C (p.Gly649Arg)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361012	NM_014251.3(SLC25A13):c.1797T>A (p.Thr599=)	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361017	NM_014251.3(SLC25A13):c.1311+3A>G	SLC25A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SLC25A13	Strong	Autosomal recessive	citrullinemia, type II, adult-onset	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A13	Orphanet:247585	Citrullinemia type II
SLC25A13	Orphanet:247598	Neonatal intrahepatic cholestasis due to citrin deficiency

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
SLC25A13	HGNC:10983	ENSG00000004864	Q9UJS0	Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A13	Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial	Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle.

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)
SLC25A13	Transporter	yes		EF_hand_dom, MCP, EF-hand-dom_pair

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
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A13	283	ubiquitous	marker	right lobe of liver, liver, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A13	1,895

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC25A13	Q9UJS0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Malate-aspartate shuttle	1	1268.9×	0.004	SLC25A13
Aspartate and asparagine metabolism	1	1038.2×	0.004	SLC25A13
Protein localization	1	190.3×	0.012	SLC25A13
Mitochondrial protein import	1	167.9×	0.012	SLC25A13
Respiratory electron transport	1	95.2×	0.015	SLC25A13
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	SLC25A13
Metabolism of amino acids and derivatives	1	67.6×	0.017	SLC25A13
Metabolism	1	11.6×	0.086	SLC25A13

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
malate-aspartate shuttle	1	1872.4×	0.002	SLC25A13
aspartate transmembrane transport	1	1404.3×	0.002	SLC25A13
mitochondrial transport	1	1203.7×	0.002	SLC25A13
ATP biosynthetic process	1	991.3×	0.002	SLC25A13
L-glutamate transmembrane transport	1	802.5×	0.002	SLC25A13
cellular respiration	1	432.1×	0.003	SLC25A13
gluconeogenesis	1	324.1×	0.003	SLC25A13
response to calcium ion	1	318.0×	0.003	SLC25A13

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
SLC25A13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC25A13	1	Binding:1

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	SLC25A13
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)
SLC25A13	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening