CTLN1
MCID: CTR172
MIFTS: 64

Citrullinemia, Classic (CTLN1)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Citrullinemia, Classic

MalaCards integrated aliases for Citrullinemia, Classic:

Name: Citrullinemia, Classic 56
Citrullinemia 56 12 74 25 58 36 13 54 43 15 71
Argininosuccinate Synthetase Deficiency 56 74 24 52 58 73
Classic Citrullinemia 12 24 52 58 73 15
Citrullinemia Type I 24 52 58 73 29 6
Ass Deficiency 56 12 24 52 58 73
Citrullinuria 56 52 25 73
Ctln1 56 24 58 73
Argininosuccinic Acid Synthetase Deficiency 24 58
Citrullinemia, Type I 56 39
Citrullinemia 1 52 73
Ctnl1 52 71
Deficiency of Citrulline-Aspartate Ligase 12
Argininosuccinic Acid Synthase Deficiency 58
Argininosuccinate Synthase Deficiency 58
Citrullinemia, Type I; Ctln1 56
Citrullinemia Classical 54
Citrullinemia Type 1 58
Cit 25

Characteristics:

Orphanet epidemiological data:

58
citrullinemia
Inheritance: Autosomal recessive; Age of onset: Adult,Neonatal; Age of death: adult,infantile;
citrullinemia type i
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages;

OMIM:

56
Miscellaneous:
neonatal onset
highly variable phenotype
incidence of 1 in 57,000
prevalence of 1 in 100,000
patients may be asymptomatic, but are at risk for metabolic decompensation

Inheritance:
autosomal recessive


HPO:

31
citrullinemia, classic:
Inheritance autosomal recessive inheritance
Onset and clinical course neonatal onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Citrullinemia, Classic

Genetics Home Reference : 25 Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two types of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes. Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up, they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. Some affected individuals develop serious liver problems. The health problems associated with type I citrullinemia are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, blind spots (scotomas), problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder. Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. Affected individuals often have specific food preferences, preferring protein-rich and fatty foods and avoiding carbohydrate-rich foods. The signs and symptoms of this disorder typically appear during adulthood (adult-onset) and can be triggered by certain medications, infections, surgery, and alcohol intake. These signs and symptoms can be life-threatening in people with adult-onset type II citrullinemia. Adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD go away within a year. In rare cases, affected individuals develop other signs and symptoms in early childhood after seeming to recover from NICCD, including delayed growth, extreme tiredness (fatigue), specific food preferences (mentioned above), and abnormal amounts of fats (lipids) in the blood (dyslipidemia). This condition is known as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). Years or even decades later, some people with NICCD or FTTDCD develop the features of adult-onset type II citrullinemia.

MalaCards based summary : Citrullinemia, Classic, also known as citrullinemia, is related to carbamoyl phosphate synthetase i deficiency, hyperammonemia due to and citrullinemia, type ii, adult-onset, and has symptoms including seizures, vomiting and ataxia. An important gene associated with Citrullinemia, Classic is ASS1 (Argininosuccinate Synthase 1), and among its related pathways/superpathways are Arginine biosynthesis and Alanine, aspartate and glutamate metabolism. The drugs Phenylacetic acid and Clotrimazole have been mentioned in the context of this disorder. Affiliated tissues include liver, testes and brain, and related phenotypes are hyperammonemia and elevated plasma citrulline

Disease Ontology : 12 An inherited urea cycle disorder that involves the accumulation of ammonia and other toxic substances in the blood.

NIH Rare Diseases : 52 Citrullinemia type 1 is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. There are four types. The classic, most severe form, occurs in newborns, while a milder, later-onset form occurs in children or adults. There's also a form that occurs during or after pregnancy, and a form with no symptoms. In the classic form, symptoms occur right after birth and include excessive sleepiness, poor appetite, vomiting, and irritability. As ammonia builds up, muscle weakness, seizures , coma, and death can occur. Citrullinemia is caused by mutations in the ASS1 gene and is inherited in an autosomal recessive pattern. This disorder is diagnosed through newborn screening and additional medical and genetic tests. Treatment includes removal of ammonia in the blood by medications and dialysis , as well as a lifelong low-protein diet. Liver transplantation is possible and, if done early in life, may eliminate the symptoms of the disorder. Left untreated, people with citrullinemia will build up very high levels of ammonia in the blood that can lead to brain damage and eventually death. Treated individuals can have normal growth and development.

KEGG : 36 Citrullinemia (CTLN) is an autosomal recessive disease caused by a deficiency of argininosuccinate synthetase/citrin and characterized primarily by elevated serum and urine citrulline levels.

UniProtKB/Swiss-Prot : 73 Citrullinemia 1: The classic form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. It is a disorder of the urea cycle, usually manifesting in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder form can develop later in childhood or adulthood.

Wikipedia : 74 Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic... more...

More information from OMIM: 215700
GeneReviews: NBK1458

Related Diseases for Citrullinemia, Classic

Diseases related to Citrullinemia, Classic via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 265)
# Related Disease Score Top Affiliating Genes
1 carbamoyl phosphate synthetase i deficiency, hyperammonemia due to 32.5 SLC25A15 OTC NAGS CPS1 ASS1 ASL
2 citrullinemia, type ii, adult-onset 32.4 SPINK1 SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12
3 argininemia 31.7 SLC25A15 SLC25A13 OTC NAGS HADHA CPS1
4 ornithine transcarbamylase deficiency, hyperammonemia due to 31.6 SLC25A15 SLC25A13 OTC NAGS MMD CPS1
5 hepatic encephalopathy 31.2 SLC25A13 ASS1 AFP
6 postpartum psychosis 30.6 OTC ASS1
7 abdominal obesity-metabolic syndrome 1 30.5 OTC ETFDH ACADM
8 carbonic anhydrase va deficiency, hyperammonemia due to 30.4 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
9 reye syndrome 30.3 OTC HADHA ETFDH ASS1 ACADM
10 tyrosinemia 30.2 SLC25A13 OTC AFP
11 lysinuric protein intolerance 30.2 OTC NAGS ASS1 ASL
12 orotic aciduria 30.2 OTC NAGS CPS1 ASS1 ASL
13 liver disease 29.8 SLC25A13 HADHA AFP ABCB11
14 maple syrup urine disease 29.7 OTC NAGS MMD HADHA ASL ACADM
15 argininosuccinic aciduria 29.3 SLC25A15 SLC25A13 OTC NAGS MMD CPS1
16 urea cycle disorder 28.6 SLC25A2 SLC25A15 SLC25A13 SLC25A12 OTC NAGS
17 citrullinemia, type ii, neonatal-onset 12.8
18 adult-onset citrullinemia type i 12.6
19 acute neonatal citrullinemia type i 12.5
20 microcephaly 17, primary, autosomal recessive 12.3
21 primary autosomal recessive microcephaly 11.8
22 microcephaly 11.8
23 primary microcephaly 11.7
24 bipolar disorder 11.6
25 x-linked cerebral adrenoleukodystrophy 11.3
26 noonan syndrome 5 11.2
27 microlissencephaly 11.2
28 parkinson disease, late-onset 10.8
29 essential tremor 10.7
30 multiple system atrophy 1 10.6
31 hepatic coma 10.6
32 supranuclear palsy, progressive, 1 10.5
33 brain edema 10.5
34 movement disease 10.5
35 dementia 10.5
36 dystonia 10.4
37 branched-chain keto acid dehydrogenase kinase deficiency 10.4 TMLHE ASS1
38 cholestasis 10.4
39 tremor 10.4
40 epileptic encephalopathy, early infantile, 39 10.4 SLC25A13 SLC25A12
41 corticobasal degeneration 10.4
42 multiple system atrophy, parkinsonian type 10.4
43 long-chain 3-hydroxyacyl-coa dehydrogenase deficiency 10.4 HADHA ACADVL ACADM
44 3-hydroxyacyl-coa dehydrogenase deficiency 10.4 HADHA ACADVL ACADM
45 rem sleep behavior disorder 10.3
46 carnitine-acylcarnitine translocase deficiency 10.3 TMLHE HADHA ACADVL
47 galactosemia iii 10.3 SLC25A13 ACADM
48 alzheimer disease 10.3
49 cardiomyopathy, dilated, 1gg 10.3 WDTC1 HADHA
50 hyperinsulinemic hypoglycemia, familial, 6 10.3 WDTC1 NAGS

Graphical network of the top 20 diseases related to Citrullinemia, Classic:



Diseases related to Citrullinemia, Classic

Symptoms & Phenotypes for Citrullinemia, Classic

Human phenotypes related to Citrullinemia, Classic:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperammonemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001987
2 elevated plasma citrulline 58 31 hallmark (90%) Very frequent (99-80%) HP:0011966
3 hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0001399
4 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
5 vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002013
6 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
7 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
8 intellectual disability, moderate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002342
9 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
10 intellectual disability, borderline 58 31 occasional (7.5%) Occasional (29-5%) HP:0006889
11 hepatic encephalopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002480
12 respiratory alkalosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001950
13 stroke 31 occasional (7.5%) HP:0001297
14 seizure 31 occasional (7.5%) HP:0001250
15 muscular hypotonia 58 31 very rare (1%) Very rare (<4-1%) HP:0001252
16 increased intracranial pressure 58 31 very rare (1%) Very rare (<4-1%) HP:0002516
17 gastroesophageal reflux 58 31 very rare (1%) Very rare (<4-1%) HP:0002020
18 intellectual disability, mild 58 31 very rare (1%) Very rare (<4-1%) HP:0001256
19 ataxia 58 31 very rare (1%) Very rare (<4-1%) HP:0001251
20 slurred speech 58 31 very rare (1%) Very rare (<4-1%) HP:0001350
21 migraine 58 31 very rare (1%) Very rare (<4-1%) HP:0002076
22 scotoma 58 31 very rare (1%) Very rare (<4-1%) HP:0000575
23 torticollis 58 31 very rare (1%) Very rare (<4-1%) HP:0000473
24 tachypnea 58 31 very rare (1%) Very rare (<4-1%) HP:0002789
25 coma 58 31 very rare (1%) Very rare (<4-1%) HP:0001259
26 loss of consciousness 58 31 very rare (1%) Very rare (<4-1%) HP:0007185
27 ankle clonus 58 31 very rare (1%) Very rare (<4-1%) HP:0011448
28 intellectual disability 31 HP:0001249
29 global developmental delay 31 HP:0001263
30 hepatomegaly 31 HP:0002240
31 seizures 58 Occasional (29-5%)
32 irritability 31 HP:0000737
33 cirrhosis 31 HP:0001394
34 headache 58 Very rare (<4-1%)
35 abnormality of the nervous system 58 Occasional (29-5%)
36 oroticaciduria 31 HP:0003218
37 hyperglutaminemia 31 HP:0003217
38 hypoargininemia 31 HP:0005961
39 episodic ammonia intoxication 31 HP:0001951
40 cerebral edema 31 HP:0002181
41 protein avoidance 31 HP:0002038

Symptoms via clinical synopsis from OMIM:

56
Abdomen Liver:
hepatomegaly
cirrhosis (in late-onset cases)

Growth Other:
failure to thrive

Neurologic Behavioral Psychiatric Manifestations:
irritability

Metabolic Features:
episodic ammonia intoxication
respiratory alkalosis

Neurologic Central Nervous System:
seizures
ataxia
lethargy
coma
cerebral edema
more
Abdomen Gastrointestinal:
vomiting
protein avoidance

Laboratory Abnormalities:
hyperammonemia
orotic aciduria
high plasma glutamine
high plasma citrulline (1000-5000 micromolar)
low plasma arginine
more

Clinical features from OMIM:

215700

UMLS symptoms related to Citrullinemia, Classic:


seizures, vomiting, ataxia, lethargy

GenomeRNAi Phenotypes related to Citrullinemia, Classic according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00249-S 9.44 ACADM AFP SLC25A15 SLC25A37
2 Decreased viability GR00381-A-1 9.44 SLC25A37
3 Decreased viability GR00386-A-1 9.44 ACADM HADHA SLC25A13 SLC25A2
4 Decreased viability GR00402-S-2 9.44 ACADM ACADVL AFP SLC25A37

MGI Mouse Phenotypes related to Citrullinemia, Classic:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.03 ABCB11 ACADM ACADVL AFP ASL ASS1
2 liver/biliary system MP:0005370 9.56 ABCB11 ACADM ACADVL AFP HADHA OTC
3 mortality/aging MP:0010768 9.55 ABCB11 ACADM ACADVL AFP ASL ASS1

Drugs & Therapeutics for Citrullinemia, Classic

Drugs for Citrullinemia, Classic (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Phenylacetic acid Approved Phase 2 103-82-2 999
2
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
3
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
4 Anti-Infective Agents Phase 2
5 4-phenylbutyric acid Phase 2
6 Antifungal Agents Phase 2
7 Sodium Benzoate Phase 2
8 Antimetabolites Phase 2
9
Ornithine Approved, Nutraceutical Phase 1 70-26-8, 3184-13-2 6262
10 Liver Extracts Phase 1
11
Nitric Oxide Approved 10102-43-9 145068
12
carbamide peroxide Approved 124-43-6
13 glutamine
14 Vaccines
15
Arginine Investigational, Nutraceutical 74-79-3 6322

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open, Prospective, Uncontrolled, Multicentre Study to Evaluate The Safety and Efficacy of Multiple Applications of Liver Cell Suspension Into The Portal Vein in Children With Urea Cycle Disorders (UCDs) Completed NCT00718627 Phase 2
2 Phase II Study of Sodium Phenylbutyrate, Sodium Benzoate, Sodium Phenylacetate, and Dietary Intervention for Urea Cycle Disorders Completed NCT00004767 Phase 2 Sodium Benzoate;Sodium Phenylacetate;Sodium Phenylbutyrate
3 Hypothermia Treatment in Hyperammonemia and Encephalopathy Completed NCT01624311 Phase 2
4 Hepatocyte Transplantation for Liver Based Metabolic Disorders Suspended NCT01345578 Phase 1 human hepatocyte transplantation
5 Evaluation of Citrullinemia as a Marker of Bowel Damage After Allogeneic Bone Marrow Transplantation in Children Unknown status NCT00751452
6 RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012) Completed NCT01610089
7 Study of Non Major Microcirculation During Extracorporeal Circulation : Relation Between Endothelial Dysfunction and Digestive Completed NCT01389947
8 Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders Recruiting NCT02935283
9 Citrullinemia for the Prediction of Enteral Nutrition Tolerance Among Critically Ill Patients Not yet recruiting NCT03967795 N2-L-Alanyl-L-Glutamine (Substance)
10 The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity Terminated NCT01421888

Search NIH Clinical Center for Citrullinemia, Classic

Cochrane evidence based reviews: citrullinemia

Genetic Tests for Citrullinemia, Classic

Genetic tests related to Citrullinemia, Classic:

# Genetic test Affiliating Genes
1 Citrullinemia Type I 29 ASS1

Anatomical Context for Citrullinemia, Classic

MalaCards organs/tissues related to Citrullinemia, Classic:

40
Liver, Testes, Brain, Bone Marrow, Bone, Endothelial, Skin

Publications for Citrullinemia, Classic

Articles related to Citrullinemia, Classic:

(show top 50) (show all 482)
# Title Authors PMID Year
1
Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. 61 56 6 24
19006241 2009
2
Pregnancy in a healthy woman with untreated citrullinemia. 61 6 56 24
15266621 2004
3
Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. 6 56 24 61
11941481 2002
4
Early cirrhosis in a patient with type I citrullinaemia (CTLN1). 6 24 56
15334737 2004
5
Nature and frequency of mutations in the argininosuccinate synthetase gene that cause classical citrullinemia. 54 61 56 6
7557970 1995
6
Additional mutations in argininosuccinate synthetase causing citrullinemia. 56 6 61
1943692 1991
7
Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. 56 6 61
2358466 1990
8
Citrullinemia: phenotypic variations. 6 56 61
934749 1976
9
A nonsense mutation is responsible for the RNA-negative phenotype in human citrullinaemia. 56 6
11571557 2001
10
Citrullinemia Type I 61 6
20301631 2004
11
Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. 24 54 61
12815590 2003
12
Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. 56 61
7977368 1994
13
Animal model of human disease. Citrullinemia (argininosuccinate synthetase deficiency). 56 61
2596577 1989
14
Molecular definition of bovine argininosuccinate synthetase deficiency. 56 61
2813370 1989
15
Structure of an abnormal messenger RNA for argininosuccinate synthetase in citrullinemia. 61 56
3570300 1987
16
Messenger RNA coding for argininosuccinate synthetase in citrullinemia. 56 61
3459354 1986
17
Level of translatable messenger RNA coding for argininosuccinate synthetase in the liver of the patients with quantitative-type citrullinemia. 61 56
3972414 1985
18
Molecular analysis of argininosuccinate synthetase deficiency in human fibroblasts. 56 61
7174798 1982
19
Qualitative and quantitative abnormalities of argininosuccinate synthetase in citrullinemia. 56 61
6784969 1981
20
Neonatal citrllinemia: treatment with keto-analogues of essential amino acids. 56 61
830913 1977
21
Somatic cell genetic evidence for the presence of a gene for citrullinemia on human chromosome 9. 56 61
891260 1977
22
A variant form of citrullinemia. 61 56
1271146 1976
23
Citrullinemia: enzymatic evidence for genetic heterogeneity. 61 56
1161343 1975
24
Citrullinemia: a new case, with implications concerning adaptation to defective urea synthesis. 56 61
5057291 1972
25
[Citrullinemia]. 56 61
5561754 1971
26
Citrullinemia with defective urea production. 61 56
6051056 1967
27
Liver transplantation for neonatal-onset citrullinemia. 61 52
29726081 2018
28
Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options. 52 61
29094226 2018
29
A longitudinal study of urea cycle disorders. 56
25135652 2014
30
High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations. 61 24
23246278 2013
31
30-year follow-up of a patient with classic citrullinemia. 61 24
22494546 2012
32
Urea cycle disorders: brain MRI and neurological outcome. 24 61
21989980 2012
33
Transient fulminant liver failure as an initial presentation in citrullinemia type I. 61 24
21227727 2011
34
Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. 24 61
20567911 2010
35
Recurrent liver failure in a 25-year-old female. 24 61
20818742 2010
36
First manifestation of citrullinemia type I as differential diagnosis to postpartum psychosis in the puerperal period. 61 24
20005624 2010
37
Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. 56
20142522 2010
38
Citrullinemia type I, classical variant. Identification of ASS-p~G390R (c.1168G>A) mutation in families of a limited geographic area of Argentina: a possible population cluster. 24 61
19358837 2009
39
Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings. 61 24
14729525 2004
40
Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). 61 24
14680976 2003
41
Urea Cycle Disorders Overview 6
20301396 2003
42
Expanded newborn screening by tandem mass spectrometry: the Massachusetts and New England experience. 61 24
15906712 2003
43
Tandem mass spectrometric analysis for disorders in amino, organic and fatty acid metabolism: two year experience in South Korea. 61 24
15906713 2003
44
Improving the prenatal diagnosis of citrullinemia using citrulline/ornithine+arginine ratio in amniotic fluid. 61 24
12116302 2002
45
CT findings in the infantile form of citrullinemia. 61 24
11847065 2002
46
Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). 61 24
12111366 2002
47
Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia. 56
11804205 2001
48
New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene. 56
1440058 1992
49
Arginosuccinate synthetase deficiency: good outcome despite severe neonatal hyperammonaemia. 56
1527997 1992
50
Assignment of the structural gene for argininosuccinate synthetase to proximal mouse chromosome 2. 56
1970331 1990

Variations for Citrullinemia, Classic

ClinVar genetic disease variations for Citrullinemia, Classic:

6 (show top 50) (show all 265) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ASS1 NC_000009.12:g.(?_130458401)_(130458589_?)deldeletion Pathogenic 458669 9:130458401-130458589
2 ASS1 NM_054012.4(ASS1):c.370G>A (p.Asp124Asn)SNV Pathogenic 458673 rs936192871 9:133339504-133339504 9:130464117-130464117
3 ASS1 NM_054012.4(ASS1):c.1128-6_1188dupduplication Pathogenic 495381 rs1554725677 9:133374882-133374883 9:130499495-130499496
4 ASS1 NM_054012.4(ASS1):c.120del (p.Lys41fs)deletion Pathogenic 528374 rs1554982237 9:133329706-133329706 9:130454319-130454319
5 ASS1 NC_000009.12:g.(?_130464091)_(130464187_?)deldeletion Pathogenic 583445 9:133339478-133339574 9:130464091-130464187
6 ASS1 NM_054012.4(ASS1):c.319del (p.Gln107fs)deletion Pathogenic 573823 rs1564903969 9:133333930-133333930 9:130458543-130458543
7 ASS1 NC_000009.12:g.(?_130452214)_(130454383_?)deldeletion Pathogenic 649068 9:133327601-133329770 9:130452214-130454383
8 ASS1 NM_054012.4(ASS1):c.352G>A (p.Ala118Thr)SNV Pathogenic 813406 9:133333965-133333965 9:130458578-130458578
9 ASS1 NM_054012.4(ASS1):c.421-2A>CSNV Pathogenic 813407 9:133342110-133342110 9:130466723-130466723
10 ASS1 NM_054012.4(ASS1):c.469C>T (p.Arg157Cys)SNV Pathogenic 813408 9:133342160-133342160 9:130466773-130466773
11 ASS1 NM_054012.4(ASS1):c.484dup (p.Glu162fs)duplication Pathogenic 813409 9:133342173-133342174 9:130466786-130466787
12 ASS1 NM_054012.4(ASS1):c.689-2A>CSNV Pathogenic 813460 9:133355101-133355101 9:130479714-130479714
13 ASS1 NM_054012.4(ASS1):c.846C>A (p.Tyr282Ter)SNV Pathogenic 840768 9:133364727-133364727 9:130489340-130489340
14 ASS1 NM_054012.4(ASS1):c.832del (p.Ser278fs)deletion Pathogenic 845376 9:133355830-133355830 9:130480443-130480443
15 ASS1 ASS1, IVS6AS, A-G, -2deletion Pathogenic 6323
16 ASS1 ASS1, EX6DELdeletion Pathogenic 6322
17 ASS1 ASS1, EX5DELdeletion Pathogenic 6321
18 ASS1 NM_054012.4(ASS1):c.774-2A>GSNV Pathogenic 813462 9:133355770-133355770 9:130480383-130480383
19 ASS1 NM_054012.4(ASS1):c.910C>T (p.Arg304Trp)SNV Pathogenic 6330 rs121908642 9:133364791-133364791 9:130489404-130489404
20 ASS1 NM_054012.4(ASS1):c.535T>C (p.Trp179Arg)SNV Pathogenic 6335 rs121908646 9:133346260-133346260 9:130470873-130470873
21 ASS1 NM_054012.4(ASS1):c.1085G>T (p.Gly362Val)SNV Pathogenic 6336 rs121908647 9:133370368-133370368 9:130494981-130494981
22 ASS1 ASS1, IVS6, G-A, +5SNV Pathogenic 6337
23 ASS1 ASS1, IVS15, G-C, -1SNV Pathogenic 6338
24 ASS1 NM_054012.4(ASS1):c.256C>T (p.Arg86Cys)SNV Pathogenic 6332 rs121908644 9:133333869-133333869 9:130458482-130458482
25 ASS1 NM_054012.4(ASS1):c.1194-1G>CSNV Pathogenic 166704 rs727503814 9:133376362-133376362 9:130500975-130500975
26 ASS1 NM_054012.4(ASS1):c.421-2A>GSNV Pathogenic 198386 rs751930594 9:133342110-133342110 9:130466723-130466723
27 ASS1 NM_054012.4(ASS1):c.257G>A (p.Arg86His)SNV Pathogenic 265960 rs575001023 9:133333870-133333870 9:130458483-130458483
28 ASS1 NM_054012.4(ASS1):c.851C>T (p.Thr284Ile)SNV Pathogenic 265961 rs886039853 9:133364732-133364732 9:130489345-130489345
29 ASS1 NM_054012.4(ASS1):c.814C>T (p.Arg272Cys)SNV Pathogenic 371132 rs762387914 9:133355812-133355812 9:130480425-130480425
30 ASS1 NM_054012.4(ASS1):c.919C>T (p.Arg307Cys)SNV Pathogenic/Likely pathogenic 265044 rs183276875 9:133364800-133364800 9:130489413-130489413
31 ASS1 NM_054012.4(ASS1):c.773+1G>ASNV Pathogenic/Likely pathogenic 371254 rs982830431 9:133355188-133355188 9:130479801-130479801
32 ASS1 NM_054012.4(ASS1):c.970+5G>ASNV Pathogenic/Likely pathogenic 265962 rs372128852 9:133364856-133364856 9:130489469-130489469
33 ASS1 NM_054012.4(ASS1):c.571G>A (p.Glu191Lys)SNV Pathogenic/Likely pathogenic 208153 rs777828000 9:133346876-133346876 9:130471489-130471489
34 ASS1 NM_054012.4(ASS1):c.450_451del (p.Phe150fs)deletion Pathogenic/Likely pathogenic 189044 rs786204648 9:133342140-133342141 9:130466753-130466754
35 ASS1 NM_054012.4(ASS1):c.892del (p.Glu298fs)deletion Pathogenic/Likely pathogenic 188832 rs770362721 9:133364773-133364773 9:130489386-130489386
36 ASS1 NM_054012.4(ASS1):c.1030C>T (p.Arg344Ter)SNV Pathogenic/Likely pathogenic 188885 rs786204537 9:133370313-133370313 9:130494926-130494926
37 ASS1 NM_054012.4(ASS1):c.835C>T (p.Arg279Ter)SNV Pathogenic/Likely pathogenic 6333 rs121908645 9:133355833-133355833 9:130480446-130480446
38 ASS1 NM_054012.4(ASS1):c.496-2A>GSNV Pathogenic/Likely pathogenic 92368 rs398123130 9:133346219-133346219 9:130470832-130470832
39 ASS1 NM_054012.4(ASS1):c.787G>A (p.Val263Met)SNV Pathogenic/Likely pathogenic 92372 rs192838388 9:133355785-133355785 9:130480398-130480398
40 ASS1 NM_054012.4(ASS1):c.794G>A (p.Arg265His)SNV Pathogenic/Likely pathogenic 92374 rs398123131 9:133355792-133355792 9:130480405-130480405
41 ASS1 NM_054012.4(ASS1):c.836G>A (p.Arg279Gln)SNV Pathogenic/Likely pathogenic 92375 rs371265106 9:133355834-133355834 9:130480447-130480447
42 ASS1 NM_054012.4(ASS1):c.40G>A (p.Gly14Ser)SNV Pathogenic/Likely pathogenic 6324 rs121908636 9:133327655-133327655 9:130452268-130452268
43 ASS1 NM_054012.4(ASS1):c.539G>A (p.Ser180Asn)SNV Pathogenic/Likely pathogenic 6326 rs121908638 9:133346264-133346264 9:130470877-130470877
44 ASS1 NM_054012.4(ASS1):c.970G>A (p.Gly324Ser)SNV Pathogenic/Likely pathogenic 6327 rs121908639 9:133364851-133364851 9:130489464-130489464
45 ASS1 NM_054012.4(ASS1):c.1087C>T (p.Arg363Trp)SNV Pathogenic/Likely pathogenic 6328 rs121908640 9:133370370-133370370 9:130494983-130494983
46 ASS1 NM_054012.4(ASS1):c.1168G>A (p.Gly390Arg)SNV Pathogenic/Likely pathogenic 6329 rs121908641 9:133374932-133374932 9:130499545-130499545
47 SLC25A13 NM_014251.3(SLC25A13):c.848+1G>TSNV Pathogenic/Likely pathogenic 802338 7:95818892-95818892 7:96189580-96189580
48 ASS1 NM_054012.4(ASS1):c.174+1G>TSNV Pathogenic/Likely pathogenic 623124 rs748264993 9:133329761-133329761 9:130454374-130454374
49 ASS1 NM_054012.4(ASS1):c.931C>T (p.Gln311Ter)SNV Pathogenic/Likely pathogenic 552773 rs1301613270 9:133364812-133364812 9:130489425-130489425
50 ASS1 NM_054012.4(ASS1):c.1069C>T (p.Gln357Ter)SNV Pathogenic/Likely pathogenic 528373 rs756859126 9:133370352-133370352 9:130494965-130494965

UniProtKB/Swiss-Prot genetic disease variations for Citrullinemia, Classic:

73 (show top 50) (show all 86)
# Symbol AA change Variation ID SNP ID
1 ASS1 p.Gly14Ser VAR_000681 rs121908636
2 ASS1 p.Ser18Leu VAR_000682 rs121908643
3 ASS1 p.Arg86Cys VAR_000683 rs121908644
4 ASS1 p.Ala118Thr VAR_000684 rs775305020
5 ASS1 p.Arg157His VAR_000685 rs121908637
6 ASS1 p.Ser180Asn VAR_000686 rs121908638
7 ASS1 p.Ala192Val VAR_000687
8 ASS1 p.Arg272Cys VAR_000688 rs762387914
9 ASS1 p.Gly280Arg VAR_000689
10 ASS1 p.Arg304Trp VAR_000690 rs121908642
11 ASS1 p.Gly324Ser VAR_000691 rs121908639
12 ASS1 p.Arg363Leu VAR_000692
13 ASS1 p.Arg363Trp VAR_000693 rs121908640
14 ASS1 p.Gly390Arg VAR_000694 rs121908641
15 ASS1 p.Cys19Arg VAR_015891
16 ASS1 p.Arg86His VAR_015892 rs575001023
17 ASS1 p.Arg95Ser VAR_015893
18 ASS1 p.Pro96Ser VAR_015894
19 ASS1 p.Gly117Ser VAR_015895 rs770944877
20 ASS1 p.Gly117Asp VAR_015896
21 ASS1 p.Arg157Cys VAR_015897 rs770585183
22 ASS1 p.Trp179Arg VAR_015898 rs121908646
23 ASS1 p.Glu191Lys VAR_015899 rs777828000
24 ASS1 p.Arg265His VAR_015900 rs398123131
25 ASS1 p.Val269Met VAR_015901 rs370595480
26 ASS1 p.Glu283Lys VAR_015902 rs765338121
27 ASS1 p.Lys310Arg VAR_015903 rs199751308
28 ASS1 p.Gly362Val VAR_015904 rs121908647
29 ASS1 p.Glu270Gln VAR_016007 rs775163147
30 ASS1 p.Arg279Gln VAR_016008 rs371265106
31 ASS1 p.Lys310Gln VAR_016009 rs121908648
32 ASS1 p.Arg363Gly VAR_016010
33 ASS1 p.Arg363Gln VAR_016011 rs771937610
34 ASS1 p.Thr389Ile VAR_016012 rs147401731
35 ASS1 p.Val69Ala VAR_016013 rs771594651
36 ASS1 p.Arg108Leu VAR_016014 rs35269064
37 ASS1 p.Thr119Ile VAR_016015
38 ASS1 p.Gln40Leu VAR_058337
39 ASS1 p.Ser79Pro VAR_058338
40 ASS1 p.Pro96His VAR_058339
41 ASS1 p.Asp124Asn VAR_058340 rs936192871
42 ASS1 p.Arg127Gln VAR_058341 rs201623252
43 ASS1 p.Arg127Trp VAR_058342 rs771794639
44 ASS1 p.Leu160Pro VAR_058343 rs969835605
45 ASS1 p.Tyr190Asp VAR_058344
46 ASS1 p.Glu191Gln VAR_058345
47 ASS1 p.Ala202Glu VAR_058346 rs376371866
48 ASS1 p.Leu206Pro VAR_058347
49 ASS1 p.Val263Met VAR_058348 rs192838388
50 ASS1 p.Arg265Cys VAR_058349 rs148918985

Expression for Citrullinemia, Classic

Search GEO for disease gene expression data for Citrullinemia, Classic.

Pathways for Citrullinemia, Classic

Pathways related to Citrullinemia, Classic according to KEGG:

36
# Name Kegg Source Accession
1 Arginine biosynthesis hsa00220
2 Alanine, aspartate and glutamate metabolism hsa00250

Pathways related to Citrullinemia, Classic according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.71 TMLHE SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12
2
Show member pathways
12.06 OTC NAGS HADHA CPS1 ASS1 ASL
3
Show member pathways
11.76 TMLHE HADHA ACADM
4 11.58 OTC CPS1 ASS1 ACADM
5
Show member pathways
11.45 HADHA ACADVL ACADM
6
Show member pathways
11.33 HADHA ACADVL ACADM
7 11.22 AFP ACADVL ACADM
8 11.1 CPS1 ASS1 ASL
9
Show member pathways
10.77 OTC NAGS CPS1 ASS1 ASL
10
Show member pathways
10.61 ASS1 ASL
11
Show member pathways
10.48 HADHA ACADM
12
Show member pathways
10.4 OTC NAGS CPS1 ASS1 ASL

GO Terms for Citrullinemia, Classic

Cellular components related to Citrullinemia, Classic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.7 TMLHE OTC NAGS ETFDH CPS1 ACADVL
2 mitochondrial inner membrane GO:0005743 9.65 SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12 OTC
3 mitochondrion GO:0005739 9.47 TMLHE SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12
4 mitochondrial nucleoid GO:0042645 9.43 HADHA CPS1 ACADVL

Biological processes related to Citrullinemia, Classic according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.91 OTC HADHA CPS1 ASS1
2 fatty acid beta-oxidation GO:0006635 9.71 HADHA ACADVL ACADM
3 cellular amino acid biosynthetic process GO:0008652 9.7 OTC ASS1 ASL
4 liver development GO:0001889 9.62 OTC CPS1 ASS1 ACADM
5 cellular response to glucagon stimulus GO:0071377 9.61 CPS1 ASS1
6 negative regulation of fatty acid biosynthetic process GO:0045717 9.6 WDTC1 ACADVL
7 L-glutamate transmembrane transport GO:0015813 9.59 SLC25A13 SLC25A12
8 response to growth hormone GO:0060416 9.58 CPS1 ASS1
9 response to amine GO:0014075 9.58 CPS1 ASS1
10 response to zinc ion GO:0010043 9.58 OTC CPS1 ASS1
11 aspartate transmembrane transport GO:0015810 9.57 SLC25A13 SLC25A12
12 L-aspartate transmembrane transport GO:0070778 9.56 SLC25A13 SLC25A12
13 carnitine biosynthetic process GO:0045329 9.55 TMLHE ACADM
14 malate-aspartate shuttle GO:0043490 9.51 SLC25A13 SLC25A12
15 citrulline biosynthetic process GO:0019240 9.49 OTC CPS1
16 mitochondrial L-ornithine transmembrane transport GO:1990575 9.48 SLC25A2 SLC25A15
17 cellular response to oleic acid GO:0071400 9.46 CPS1 ASS1
18 arginine biosynthetic process via ornithine GO:0042450 9.43 OTC ASL
19 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.43 ETFDH ACADVL ACADM
20 anion homeostasis GO:0055081 9.37 OTC CPS1
21 midgut development GO:0007494 9.33 OTC CPS1 ASS1
22 arginine biosynthetic process GO:0006526 9.26 OTC NAGS ASS1 ASL
23 urea cycle GO:0000050 9.17 SLC25A2 SLC25A15 OTC NAGS CPS1 ASS1

Molecular functions related to Citrullinemia, Classic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.77 TMLHE HADHA ETFDH ACADVL ACADM
2 ATP transmembrane transporter activity GO:0005347 9.46 SLC25A13 SLC25A12
3 fatty-acyl-CoA binding GO:0000062 9.43 HADHA ACADVL
4 amino acid binding GO:0016597 9.4 OTC ASS1
5 L-glutamate transmembrane transporter activity GO:0005313 9.32 SLC25A13 SLC25A12
6 acyl-CoA dehydrogenase activity GO:0003995 9.26 ACADVL ACADM
7 L-aspartate transmembrane transporter activity GO:0015183 9.16 SLC25A13 SLC25A12
8 flavin adenine dinucleotide binding GO:0050660 9.13 ETFDH ACADVL ACADM
9 L-ornithine transmembrane transporter activity GO:0000064 8.62 SLC25A2 SLC25A15

Sources for Citrullinemia, Classic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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