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 57
Citrullinemia 57 12 73 43 58 36 29 13 54 6 44 15 70
Argininosuccinate Synthetase Deficiency 57 73 25 20 58 72
Classic Citrullinemia 12 25 20 58 72 15
Citrullinemia Type I 25 20 58 72 29 6
Ass Deficiency 57 12 25 20 58 72
Citrullinuria 57 20 43 72
Ctln1 57 25 58 72
Argininosuccinic Acid Synthetase Deficiency 25 58
Citrullinemia, Type I 57 39
Citrullinemia 1 20 72
Ctnl1 20 70
Deficiency of Citrulline-Aspartate Ligase 12
Argininosuccinic Acid Synthase Deficiency 58
Argininosuccinate Synthase Deficiency 58
Citrullinemia, Type I; Ctln1 57
Citrullinemia Classical 54
Citrullinemia Type 1 58
Cit 43

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®:

57 (Updated 05-Apr-2021)
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

MedlinePlus Genetics : 43 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, ataxia and vomiting. 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 carbamide peroxide and Ornithine have been mentioned in the context of this disorder. Affiliated tissues include liver, brain and bone marrow, 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.

GARD : 20 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 : 72 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 : 73 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 246)
# Related Disease Score Top Affiliating Genes
1 carbamoyl phosphate synthetase i deficiency, hyperammonemia due to 32.0 SLC25A15 OTC NAGS CPS1 ASS1
2 citrullinemia, type ii, adult-onset 31.3 SPINK1 SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12
3 ornithine transcarbamylase deficiency, hyperammonemia due to 31.3 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
4 argininemia 31.1 SLC25A15 SLC25A13 OTC NAGS HADHA CPS1
5 carbonic anhydrase va deficiency, hyperammonemia due to 30.5 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
6 reye syndrome 30.5 OTC ETFDH ASS1
7 postpartum psychosis 30.5 OTC ASS1
8 cholestasis 30.2 SLC25A13 HSD3B7 HADHA ABCB11
9 abdominal obesity-metabolic syndrome 1 30.1 OTC HADHA ETFDH
10 orotic aciduria 30.0 OTC NAGS CPS1 ASS1 ASL
11 lysinuric protein intolerance 29.9 OTC NAGS ASS1 ASL
12 liver disease 29.7 SLC25A13 HSD3B7 HADHA ABCB11
13 maple syrup urine disease 29.6 OTC NAGS HADHA CPS1 ASS1 ASL
14 argininosuccinic aciduria 29.4 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
15 urea cycle disorder 28.9 SLC25A2 SLC25A15 SLC25A13 SLC25A12 OTC NAGS
16 citrullinemia, type ii, neonatal-onset 11.7
17 adult-onset citrullinemia type i 11.4
18 microcephaly 17, primary, autosomal recessive 11.4
19 acute neonatal citrullinemia type i 11.3
20 microcephaly 11.2
21 primary autosomal recessive microcephaly 11.1
22 primary microcephaly 11.1
23 bipolar disorder 11.1
24 noonan syndrome 5 10.9
25 microlissencephaly 10.9
26 long qt syndrome 10.9
27 parkinsonism 10.8
28 parkinson disease, late-onset 10.7
29 essential tremor 10.6
30 dementia 10.5
31 multiple system atrophy 1 10.5
32 supranuclear palsy, progressive, 1 10.4
33 hepatic coma 10.4
34 hepatic encephalopathy 10.4
35 vascular parkinsonism 10.4
36 movement disease 10.4
37 dystonia 10.3
38 brain edema 10.3
39 acyl-coa dehydrogenase deficiency 10.3 ETFDH ACADVL
40 corticobasal degeneration 10.3
41 multiple system atrophy, parkinsonian type 10.3
42 developmental and epileptic encephalopathy 39 10.3 SLC25A13 SLC25A12
43 tremor 10.2
44 tyrosinemia, type i 10.2 OTC NAGS ASL
45 alzheimer disease 10.2
46 autosomal recessive disease 10.2
47 acute liver failure 10.2
48 rem sleep behavior disorder 10.2
49 pyrimidine metabolic disorder 10.2 OTC NAGS ASS1 ASL
50 acyl-coa dehydrogenase, short-chain, deficiency of 10.2 HADHA ETFDH ACADVL

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 42)
# 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 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
5 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
6 vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002013
7 intellectual disability, moderate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002342
8 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
9 intellectual disability, borderline 58 31 occasional (7.5%) Occasional (29-5%) HP:0006889
10 feeding difficulties 58 31 occasional (7.5%) Occasional (29-5%) HP:0011968
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 ataxia 58 31 very rare (1%) Very rare (<4-1%) HP:0001251
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 slurred speech 58 31 very rare (1%) Very rare (<4-1%) HP:0001350
20 migraine 58 31 very rare (1%) Very rare (<4-1%) HP:0002076
21 scotoma 58 31 very rare (1%) Very rare (<4-1%) HP:0000575
22 torticollis 58 31 very rare (1%) Very rare (<4-1%) HP:0000473
23 tachypnea 58 31 very rare (1%) Very rare (<4-1%) HP:0002789
24 coma 58 31 very rare (1%) Very rare (<4-1%) HP:0001259
25 loss of consciousness 58 31 very rare (1%) Very rare (<4-1%) HP:0007185
26 ankle clonus 58 31 very rare (1%) Very rare (<4-1%) HP:0011448
27 hypotonia 31 very rare (1%) HP:0001252
28 intellectual disability 31 HP:0001249
29 seizures 58 Occasional (29-5%)
30 muscular hypotonia 58 Very rare (<4-1%)
31 global developmental delay 31 HP:0001263
32 hepatomegaly 31 HP:0002240
33 cirrhosis 31 HP:0001394
34 irritability 31 HP:0000737
35 headache 58 Very rare (<4-1%)
36 abnormality of the nervous system 58 Occasional (29-5%)
37 oroticaciduria 31 HP:0003218
38 hyperglutaminemia 31 HP:0003217
39 hypoargininemia 31 HP:0005961
40 episodic ammonia intoxication 31 HP:0001951
41 cerebral edema 31 HP:0002181
42 protein avoidance 31 HP:0002038

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
lethargy
coma
cerebral edema
more
Abdomen Liver:
hepatomegaly
cirrhosis (in late-onset cases)

Neurologic Behavioral Psychiatric Manifestations:
irritability

Metabolic Features:
episodic ammonia intoxication
respiratory alkalosis

Growth Other:
failure to thrive

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 (Updated 05-Apr-2021)

UMLS symptoms related to Citrullinemia, Classic:


seizures; ataxia; vomiting; 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 9.47 ARG2 HSD3B7 SLC25A15 SLC25A37
2 Decreased viability GR00381-A-1 9.47 HSD3B7 SLC25A37
3 Decreased viability GR00386-A-1 9.47 ANGPTL6 ARG2 HADHA HSD3B7 SLC25A13 SLC25A2
4 Decreased viability GR00402-S-2 9.47 ACADVL SLC25A37

MGI Mouse Phenotypes related to Citrullinemia, Classic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.06 ABCB11 ACADVL ANGPTL6 ARG1 ARG2 ASL
2 growth/size/body region MP:0005378 10.03 ABCB11 ACADVL ANGPTL6 ASL ASS1 HADHA
3 liver/biliary system MP:0005370 9.56 ABCB11 ACADVL ARG1 HADHA HSD3B7 OTC
4 mortality/aging MP:0010768 9.55 ABCB11 ACADVL ANGPTL6 ARG1 ASL ASS1

Drugs & Therapeutics for Citrullinemia, Classic

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

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
carbamide peroxide Approved Phase 2 124-43-6
2
Ornithine Approved, Nutraceutical Phase 2 70-26-8, 3184-13-2 6262
3 Liver Extracts Phase 2
4
Arginine Investigational, Nutraceutical Phase 1 74-79-3 6322
5
Nitric Oxide Approved 10102-43-9 145068
6 glutamine
7 Vaccines

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 A Phase 1 Study of ADI PEG 20 in Pediatric Subjects Who Are Argininosuccinate Synthetase (ASS) Deficient and Have Failed Prior Systemic Therapy Completed NCT01528384 Phase 1 ADI-PEG 20
3 Evaluation of Citrullinemia as a Marker of Bowel Damage After Allogeneic Bone Marrow Transplantation in Children Unknown status NCT00751452
4 RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012) Completed NCT01610089
5 Study of Non Major Microcirculation During Extracorporeal Circulation : Relation Between Endothelial Dysfunction and Digestive Completed NCT01389947
6 Citrullinemia for the Prediction of Enteral Nutrition Tolerance Among Critically Ill Patients Not yet recruiting NCT03967795 N2-L-Alanyl-L-Glutamine (Substance)
7 Noninvasive Biomarkers of Hepatic Fibrosis in Urea Cycle Disorders Not yet recruiting NCT04612764
8 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
2 Citrullinemia 29

Anatomical Context for Citrullinemia, Classic

MalaCards organs/tissues related to Citrullinemia, Classic:

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

Publications for Citrullinemia, Classic

Articles related to Citrullinemia, Classic:

(show top 50) (show all 530)
# Title Authors PMID Year
1
Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. 54 61 57 25 6
19006241 2009
2
Pregnancy in a healthy woman with untreated citrullinemia. 25 57 6 61 54
15266621 2004
3
Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. 61 6 54 25 57
11941481 2002
4
Early cirrhosis in a patient with type I citrullinaemia (CTLN1). 57 6 25
15334737 2004
5
Nature and frequency of mutations in the argininosuccinate synthetase gene that cause classical citrullinemia. 57 61 54 6
7557970 1995
6
Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. 54 61 6 57
7977368 1994
7
Additional mutations in argininosuccinate synthetase causing citrullinemia. 61 54 57 6
1943692 1991
8
Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. 57 6 54 61
2358466 1990
9
Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). 6 25 54 61
14680976 2003
10
Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. 54 61 25 6
12815590 2003
11
Citrullinemia: phenotypic variations. 57 61 6
934749 1976
12
High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations. 61 25 6
23246278 2013
13
Transient fulminant liver failure as an initial presentation in citrullinemia type I. 25 61 6
21227727 2011
14
First manifestation of citrullinemia type I as differential diagnosis to postpartum psychosis in the puerperal period. 6 25 61
20005624 2010
15
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. 61 25 6
19358837 2009
16
A nonsense mutation is responsible for the RNA-negative phenotype in human citrullinaemia. 57 6
11571557 2001
17
Cross-sectional observational study of 208 patients with non-classical urea cycle disorders. 6 25
23780642 2014
18
Investigation of citrullinemia type I variants by in vitro expression studies. 6 54 61
18473344 2008
19
Argininosuccinate synthetase deficiency: mutation analysis in 3 Thai patients. 6 54 61
16124451 2005
20
Mutation analysis of Korean patients with citrullinemia. 6 61 54
10987146 2000
21
Mutations and DNA diagnoses of classical citrullinemia. 54 6 61
9090528 1997
22
Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells. 6 54 61
8792870 1994
23
Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing. 6 61
30285816 2018
24
Identification of three novel mutations in fourteen patients with citrullinemia type 1. 6 61
28132756 2017
25
Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs. 6 61
28302489 2017
26
Mutations in the Human Argininosuccinate Synthetase (ASS1) Gene, Impact on Patients, Common Changes, and Structural Considerations. 6 61
28111830 2017
27
Kinetic mutations in argininosuccinate synthetase deficiency: characterisation and in vitro correction by substrate supplementation. 6 61
27287393 2016
28
Functional analysis of novel splicing and missense mutations identified in the ASS1 gene in classical citrullinemia patients. 6 61
25179242 2015
29
Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements. 6 61
24713661 2015
30
Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases. 6 61
25433810 2014
31
[ASS1 gene mutation in a neonate with citrullinemia type I]. 61 6
25537548 2014
32
Improved standards for prenatal diagnosis of citrullinemia. 61 6
24889030 2014
33
Molecular genetics of citrullinemia types I and II. 61 6
24508627 2014
34
Prenatal diagnosis of citrullinemia type 1: a Chinese family with a novel mutation of the ASS1 gene. 6 61
23611581 2014
35
Mutation spectrum of the ASS1 gene in Korean patients with citrullinemia type I. 6 61
23099195 2013
36
Citrullinemia type I and hypertrophic pyloric stenosis in a 1-month old male infant. 61 6
24765495 2013
37
Unrecognized citrullinemia mimicking encephalitis in a 14-year-old boy: unexpected result through the use of a standardized lumbar puncture protocol. 6 61
22473243 2012
38
Molecular epidemiology of citrullinemia type I in a risk region of Argentina: a first step to preconception heterozygote detection. 61 6
23430935 2012
39
Leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis. 61 6
23094117 2012
40
Successful prospective management of neonatal citrullinemia. 61 6
22768672 2012
41
The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia. 6 61
18925679 2008
42
Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. 61 6
16475226 2006
43
Postpartum "psychosis" in mild argininosuccinate synthetase deficiency. 6 54
15863597 2005
44
The 1.6 A crystal structure of E. coli argininosuccinate synthetase suggests a conformational change during catalysis. 6 61
11738042 2001
45
Phenotype and genotype heterogeneity in Mediterranean citrullinemia. 6 61
11708871 2001
46
The first successful prenatal diagnosis on a Korean family with citrullinemia. 6 61
11211875 2000
47
Analysis of a splice acceptor site mutation which produces multiple splicing abnormalities in the human argininosuccinate synthetase locus. 6 61
2246255 1990
48
Animal model of human disease. Citrullinemia (argininosuccinate synthetase deficiency). 61 57
2596577 1989
49
Molecular definition of bovine argininosuccinate synthetase deficiency. 61 57
2813370 1989
50
Analysis of deletions at the human argininosuccinate synthetase locus. 6 61
2615645 1989

Variations for Citrullinemia, Classic

ClinVar genetic disease variations for Citrullinemia, Classic:

6 (show top 50) (show all 322)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ASS1 ASS1, EX5DEL Deletion Pathogenic 6321 GRCh37:
GRCh38:
2 ASS1 ASS1, EX6DEL Deletion Pathogenic 6322 GRCh37:
GRCh38:
3 ASS1 ASS1, IVS6AS, A-G, -2 Deletion Pathogenic 6323 GRCh37:
GRCh38:
4 ASS1 NM_054012.4(ASS1):c.256C>T (p.Arg86Cys) SNV Pathogenic 6332 rs121908644 GRCh37: 9:133333869-133333869
GRCh38: 9:130458482-130458482
5 ASS1 ASS1, IVS6, G-A, +5 SNV Pathogenic 6337 GRCh37:
GRCh38:
6 ASS1 ASS1, IVS15, G-C, -1 SNV Pathogenic 6338 GRCh37:
GRCh38:
7 ASS1 NM_054012.4(ASS1):c.814C>T (p.Arg272Cys) SNV Pathogenic 371132 rs762387914 GRCh37: 9:133355812-133355812
GRCh38: 9:130480425-130480425
8 ASS1 NM_054012.4(ASS1):c.370G>A (p.Asp124Asn) SNV Pathogenic 458673 rs936192871 GRCh37: 9:133339504-133339504
GRCh38: 9:130464117-130464117
9 ASS1 NC_000009.12:g.(?_130458401)_(130458589_?)del Deletion Pathogenic 458669 GRCh37:
GRCh38: 9:130458401-130458589
10 ASS1 NM_054012.4(ASS1):c.120del (p.Lys41fs) Deletion Pathogenic 528374 rs1554982237 GRCh37: 9:133329706-133329706
GRCh38: 9:130454319-130454319
11 ASS1 NC_000009.12:g.(?_130464091)_(130464187_?)del Deletion Pathogenic 583445 GRCh37: 9:133339478-133339574
GRCh38: 9:130464091-130464187
12 ASS1 NC_000009.12:g.(?_130452214)_(130454383_?)del Deletion Pathogenic 649068 GRCh37: 9:133327601-133329770
GRCh38: 9:130452214-130454383
13 SLC25A13 NM_014251.3(SLC25A13):c.848+1G>T SNV Pathogenic 802338 rs761370420 GRCh37: 7:95818892-95818892
GRCh38: 7:96189580-96189580
14 ASS1 NM_054012.4(ASS1):c.352G>A (p.Ala118Thr) SNV Pathogenic 813406 rs775305020 GRCh37: 9:133333965-133333965
GRCh38: 9:130458578-130458578
15 ASS1 NM_054012.4(ASS1):c.421-2A>C SNV Pathogenic 813407 rs751930594 GRCh37: 9:133342110-133342110
GRCh38: 9:130466723-130466723
16 ASS1 NM_054012.4(ASS1):c.469C>T (p.Arg157Cys) SNV Pathogenic 813408 rs770585183 GRCh37: 9:133342160-133342160
GRCh38: 9:130466773-130466773
17 ASS1 NM_054012.4(ASS1):c.484dup (p.Glu162fs) Duplication Pathogenic 813409 rs1313340299 GRCh37: 9:133342173-133342174
GRCh38: 9:130466786-130466787
18 ASS1 NM_054012.4(ASS1):c.774-2A>G SNV Pathogenic 813462 rs1588496214 GRCh37: 9:133355770-133355770
GRCh38: 9:130480383-130480383
19 ASS1 NM_054012.4(ASS1):c.846C>A (p.Tyr282Ter) SNV Pathogenic 840768 GRCh37: 9:133364727-133364727
GRCh38: 9:130489340-130489340
20 ASS1 NM_054012.4(ASS1):c.832del (p.Ser278fs) Deletion Pathogenic 845376 GRCh37: 9:133355830-133355830
GRCh38: 9:130480443-130480443
21 ASS1 NM_054012.4(ASS1):c.356C>T (p.Thr119Ile) SNV Pathogenic 939977 GRCh37: 9:133333969-133333969
GRCh38: 9:130458582-130458582
22 ASS1 NM_054012.4(ASS1):c.339T>G (p.Tyr113Ter) SNV Pathogenic 945859 GRCh37: 9:133333952-133333952
GRCh38: 9:130458565-130458565
23 ASS1 NM_054012.4(ASS1):c.830A>G (p.Lys277Arg) SNV Pathogenic 973471 GRCh37: 9:133355828-133355828
GRCh38: 9:130480441-130480441
24 ASS1 NM_054012.4(ASS1):c.479T>C (p.Leu160Pro) SNV Pathogenic 993037 GRCh37: 9:133342170-133342170
GRCh38: 9:130466783-130466783
25 ASS1 NM_054012.4(ASS1):c.689-2A>C SNV Pathogenic 813460 rs374586230 GRCh37: 9:133355101-133355101
GRCh38: 9:130479714-130479714
26 ASS1 NM_054012.4(ASS1):c.421-2A>G SNV Pathogenic 198386 rs751930594 GRCh37: 9:133342110-133342110
GRCh38: 9:130466723-130466723
27 ASS1 NM_054012.4(ASS1):c.1128-6_1188dup Duplication Pathogenic 495381 rs1554725677 GRCh37: 9:133374882-133374883
GRCh38: 9:130499495-130499496
28 ASS1 NM_054012.4(ASS1):c.323G>T (p.Arg108Leu) SNV Pathogenic 6334 rs35269064 GRCh37: 9:133333936-133333936
GRCh38: 9:130458549-130458549
29 ASS1 NM_054012.4(ASS1):c.919C>T (p.Arg307Cys) SNV Pathogenic 265044 rs183276875 GRCh37: 9:133364800-133364800
GRCh38: 9:130489413-130489413
30 ASS1 NM_054012.4(ASS1):c.847G>A (p.Glu283Lys) SNV Pathogenic 430139 rs765338121 GRCh37: 9:133364728-133364728
GRCh38: 9:130489341-130489341
31 ASS1 NM_054012.4(ASS1):c.910C>T (p.Arg304Trp) SNV Pathogenic 6330 rs121908642 GRCh37: 9:133364791-133364791
GRCh38: 9:130489404-130489404
32 ASS1 NM_054012.4(ASS1):c.470G>A (p.Arg157His) SNV Pathogenic 6325 rs121908637 GRCh37: 9:133342161-133342161
GRCh38: 9:130466774-130466774
33 ASS1 NM_054012.4(ASS1):c.1194-1G>C SNV Pathogenic 166704 rs727503814 GRCh37: 9:133376362-133376362
GRCh38: 9:130500975-130500975
34 ASS1 NM_054012.4(ASS1):c.257G>A (p.Arg86His) SNV Pathogenic 265960 rs575001023 GRCh37: 9:133333870-133333870
GRCh38: 9:130458483-130458483
35 ASS1 NM_054012.4(ASS1):c.851C>T (p.Thr284Ile) SNV Pathogenic 265961 rs886039853 GRCh37: 9:133364732-133364732
GRCh38: 9:130489345-130489345
36 ASS1 NM_054012.4(ASS1):c.535T>C (p.Trp179Arg) SNV Pathogenic 6335 rs121908646 GRCh37: 9:133346260-133346260
GRCh38: 9:130470873-130470873
37 ASS1 NM_054012.4(ASS1):c.1085G>T (p.Gly362Val) SNV Pathogenic 6336 rs121908647 GRCh37: 9:133370368-133370368
GRCh38: 9:130494981-130494981
38 ASS1 NM_054012.4(ASS1):c.793C>T (p.Arg265Cys) SNV Pathogenic 92373 rs148918985 GRCh37: 9:133355791-133355791
GRCh38: 9:130480404-130480404
39 ASS1 NM_054012.4(ASS1):c.805G>A (p.Val269Met) SNV Pathogenic 193968 rs370595480 GRCh37: 9:133355803-133355803
GRCh38: 9:130480416-130480416
40 ASS1 NM_054012.4(ASS1):c.836G>A (p.Arg279Gln) SNV Pathogenic 92375 rs371265106 GRCh37: 9:133355834-133355834
GRCh38: 9:130480447-130480447
41 ASS1 NM_054012.4(ASS1):c.812dup (p.Asn271fs) Duplication Pathogenic 1034022 GRCh37: 9:133355808-133355809
GRCh38: 9:130480421-130480422
42 ASS1 NM_054012.4(ASS1):c.349G>A (p.Gly117Ser) SNV Pathogenic/Likely pathogenic 556029 rs770944877 GRCh37: 9:133333962-133333962
GRCh38: 9:130458575-130458575
43 ASS1 NM_054012.4(ASS1):c.892del (p.Glu298fs) Deletion Pathogenic/Likely pathogenic 188832 rs770362721 GRCh37: 9:133364773-133364773
GRCh38: 9:130489386-130489386
44 ASS1 NM_054012.4(ASS1):c.1030C>T (p.Arg344Ter) SNV Pathogenic/Likely pathogenic 188885 rs786204537 GRCh37: 9:133370313-133370313
GRCh38: 9:130494926-130494926
45 ASS1 NM_054012.4(ASS1):c.805G>A (p.Val269Met) SNV Pathogenic/Likely pathogenic 193968 rs370595480 GRCh37: 9:133355803-133355803
GRCh38: 9:130480416-130480416
46 ASS1 NM_054012.4(ASS1):c.571G>A (p.Glu191Lys) SNV Pathogenic/Likely pathogenic 208153 rs777828000 GRCh37: 9:133346876-133346876
GRCh38: 9:130471489-130471489
47 ASS1 NM_054012.4(ASS1):c.1087C>T (p.Arg363Trp) SNV Pathogenic/Likely pathogenic 6328 rs121908640 GRCh37: 9:133370370-133370370
GRCh38: 9:130494983-130494983
48 ASS1 NM_054012.4(ASS1):c.1168G>A (p.Gly390Arg) SNV Pathogenic/Likely pathogenic 6329 rs121908641 GRCh37: 9:133374932-133374932
GRCh38: 9:130499545-130499545
49 ASS1 NM_054012.4(ASS1):c.836G>A (p.Arg279Gln) SNV Pathogenic/Likely pathogenic 92375 rs371265106 GRCh37: 9:133355834-133355834
GRCh38: 9:130480447-130480447
50 ASS1 NM_054012.4(ASS1):c.835C>T (p.Arg279Ter) SNV Pathogenic/Likely pathogenic 6333 rs121908645 GRCh37: 9:133355833-133355833
GRCh38: 9:130480446-130480446

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

72 (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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 TMLHE SLC25A37 SLC25A2 SLC25A15 SLC25A13 SLC25A12
2
Show member pathways
13.54 TMLHE SLC25A2 SLC25A15 OTC NAGS CPS1
3 12.25 SLC25A12 ASS1 ARG2 ARG1
4
Show member pathways
12.13 OTC NAGS CPS1 ASS1 ASL ARG2
5 11.68 OTC CPS1 ASS1 ARG2 ARG1
6 11.11 CPS1 ASS1 ASL
7
Show member pathways
10.93 OTC NAGS CPS1 ASS1 ASL ARG2
8
Show member pathways
10.55 ASS1 ASL
9
Show member pathways
10.55 OTC NAGS CPS1 ASS1 ASL ARG2

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 ARG2
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 27)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 10.03 TMLHE HSD3B7 HADHA ETFDH ACADVL
2 response to drug GO:0042493 9.95 OTC HADHA CPS1 ASS1 ARG1
3 cellular amino acid biosynthetic process GO:0008652 9.75 OTC ASS1 ASL
4 response to amino acid GO:0043200 9.67 CPS1 ASS1 ARG1
5 liver development GO:0001889 9.67 OTC CPS1 ASS1 ARG1
6 response to steroid hormone GO:0048545 9.65 CPS1 ASS1 ARG1
7 transport GO:0006810 9.63 SLC25A13 SLC25A12
8 cellular response to glucagon stimulus GO:0071377 9.63 CPS1 ASS1 ARG1
9 L-glutamate transmembrane transport GO:0015813 9.62 SLC25A13 SLC25A12
10 response to growth hormone GO:0060416 9.62 CPS1 ASS1
11 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.61 ETFDH ACADVL
12 aspartate transmembrane transport GO:0015810 9.61 SLC25A13 SLC25A12
13 L-aspartate transmembrane transport GO:0070778 9.6 SLC25A13 SLC25A12
14 arginine metabolic process GO:0006525 9.59 ARG2 ARG1
15 cellular response to ammonium ion GO:0071242 9.58 CPS1 ASS1
16 malate-aspartate shuttle GO:0043490 9.57 SLC25A13 SLC25A12
17 citrulline biosynthetic process GO:0019240 9.56 OTC CPS1
18 mitochondrial L-ornithine transmembrane transport GO:1990575 9.54 SLC25A2 SLC25A15
19 cellular response to oleic acid GO:0071400 9.52 CPS1 ASS1
20 arginine biosynthetic process via ornithine GO:0042450 9.51 OTC ASL
21 response to amine GO:0014075 9.5 CPS1 ASS1 ARG1
22 response to zinc ion GO:0010043 9.46 OTC CPS1 ASS1 ARG1
23 anion homeostasis GO:0055081 9.43 OTC CPS1
24 midgut development GO:0007494 9.43 OTC CPS1 ASS1
25 arginine catabolic process to ornithine GO:0019547 9.4 ARG2 ARG1
26 urea cycle GO:0000050 9.28 SLC25A2 SLC25A15 OTC NAGS CPS1 ASS1
27 arginine biosynthetic process GO:0006526 9.26 OTC NAGS ASS1 ASL

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

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 10 SLC25A13 SLC25A12 OTC ASS1 ASL ARG1
2 oxidoreductase activity GO:0016491 9.77 TMLHE HSD3B7 HADHA ETFDH ACADVL
3 amino acid binding GO:0016597 9.43 OTC ASS1
4 fatty-acyl-CoA binding GO:0000062 9.4 HADHA ACADVL
5 L-glutamate transmembrane transporter activity GO:0005313 9.32 SLC25A13 SLC25A12
6 L-aspartate transmembrane transporter activity GO:0015183 9.26 SLC25A13 SLC25A12
7 L-ornithine transmembrane transporter activity GO:0000064 9.16 SLC25A2 SLC25A15
8 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines GO:0016813 8.96 ARG2 ARG1
9 arginase activity GO:0004053 8.62 ARG2 ARG1

Sources for Citrullinemia, Classic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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