HHH SYNDROME
MCID: HYP774
MIFTS: 49

Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (HHH SYNDROME)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

MalaCards integrated aliases for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

Name: Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 58 25 54 26 60 76 38 30 6
Hhh Syndrome 58 12 77 25 54 26 60 76 56 74
Ornithine Translocase Deficiency 58 12 54 26 60 15
Hyperornithinemia-Hyperammonemia-Homocitrullinemia Syndrome 58 26 13 41
Triple H Syndrome 26 60
Hhhs 58 54
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 12
Hyperornithinemia, Hyperammonemia, Homocitrullinuria Syndrome 77
Mitochondrial Ornithine Transporter Deficiency 25
Ornithine Translocase Deficiency Syndrome 54
Ornithine Carrier Deficiency 60
Hhh Syndrome; Hhhs; Hhh 58
Ornt1 Deficiency 60
Hhh 54

Characteristics:

Orphanet epidemiological data:

60
hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
Inheritance: Autosomal recessive; Prevalence: 1-5/10000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy,Neonatal; Age of death: infantile;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
phenotypic variability
onset in first months or years of life
increased prevalence in the french-canadian population


HPO:

33
hyperornithinemia-hyperammonemia-homocitrullinuria syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Inborn errors of metabolism


Summaries for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 415Disease definitionHyperornithinemia-hyperammonemia-homocitrullinuria syndrome (triple H syndrome) is a disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or chronic liver dysfunction.EpidemiologyMore than 100 cases have been reported in the literature to date. The prevalence in Northern Saskatchewan, Canada is especially high due to a founder effect and is estimated in this population at 1/1550 live births.Clinical descriptionAge of onset can range from the neonatal period to adulthood and a wide phenotypic spectrum is noted. The neonatal presentation usually begins a few days after birth with lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, and/or seizures. Onset of symptoms (ranging from mild to severe) in the majority of patients occurs in infancy, childhood and adulthood with episodes of confusion, forgetfulness, hyperammonemic coma, intellectual disability, developmental delay, spastic paraplegia, cerebellar ataxia, learning difficulties, unexplained seizures, liver dysfunction (rarely failure) and coagulopathy with factor VII-, IX- and X-deficiencies. An aversion to protein-rich foods before diagnosis is often reported.EtiologyTriple H syndrome is due to mutations in the SLC25A15 gene (13q14) encoding the mitochondrial ornithine transporter 1 (ORNT1) which plays a role in ornithine transport across the mitochondrial membrane and consecutively in mitochondrial protein synthesis, metabolism of arginine and lysine, and synthesis of polyamines. Mutations in this protein disrupt the urea cycle, resulting in hyperornithinemia, hyperammonemia and homocitrullinuria. Patients with a complete ORNT1 deficiency present in the neonatal period with severe hyperammonemia whereas those with a partial deficiency present later in infancy to adulthood.Diagnostic methodsDiagnosis is based on clinical findings and specific metabolic abnormalities. Laboratory tests usually reveal increased urinary excretion of orotic acid, homocitrulline and uracil, and a rise in the levels of plasma polyamines, ornithine, glutamine, alanine, and liver transaminases. Plasma ammonia levels are elevated episodically or postprandially and plasma ornithine is chronically elevated and is a hallmark of the disease. Molecular genetic testing confirms diagnosis.Differential diagnosisDifferential diagnosis includes other urea cycle disorders as well as lysinuric protein intolerance (see these terms). Hyperinsulinism-hyperammonemia syndrome, pyruvate carboxylase deficiency (see these terms) and secondary causes of hyperammonemia should also be considered.Antenatal diagnosisPrenatal diagnosis is possible in families with a known disease causing mutation on both alleles.Genetic counselingTriple H syndrome is inherited autosomal recessively and genetic counseling is advised.Management and treatmentTreatment involves the adherence to a low protein diet along with citrulline or arginine supplementation. In resistant cases, sodium benzoate and phenylbutyrate may be necessary for control of plasma ammonia levels. Patients should be monitored during times of stress (e.g. pregnancy, surgery, intercurrent infections) and when taking certain medications (i.e. corticosteroids) as they can trigger an episode of hyperammonemia. Hyperammonemic coma is treated in a tertiary care center where plasma ammonia levels must be lowered (by hemodialysis or hemofiltration), ammonia scavenger therapy implemented, catabolism reversed (with glucose and lipid infusions) and special care taken to reduce the risk of neurological damage.PrognosisWith early diagnosis and proper adherence to treatment protocol the prognosis is better than for most other urea cycle defects. However, patients remain at risk for metabolic decompensation throughout life and irreversible neurological complications can occur if treatment is delayed.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome, also known as hhh syndrome, is related to urea cycle disorder and ornithinemia, and has symptoms including seizures, clonus and lethargy. An important gene associated with Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome is SLC25A15 (Solute Carrier Family 25 Member 15), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. Affiliated tissues include liver, testes and brain, and related phenotypes are intellectual disability and chorioretinal atrophy

Disease Ontology : 12 An amino acid metabolic disorder that has_material_basis in deficiency of ornithine translocase resulting in the accumulation of ammonia in the blood.

Genetics Home Reference : 26 Ornithine translocase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

UniProtKB/Swiss-Prot : 76 Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: Autosomal recessive disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. It causes a functional impairment of the urea cycle.

Wikipedia : 77 Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)... more...

Description from OMIM: 238970
GeneReviews: NBK97260

Related Diseases for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Diseases related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 urea cycle disorder 30.5 ASS1 CPS1 NAGS OTC SLC25A15
2 ornithinemia 11.1
3 acute liver failure 10.5
4 postpartum psychosis 10.2 ASS1 OTC
5 gyrate atrophy of choroid and retina 10.1 OAT SLC25A15
6 orotic aciduria 10.1 ASS1 OTC
7 cerebral creatine deficiency syndrome 3 10.1 OAT SLC6A8
8 spastic paraparesis 10.1 ALDH18A1 SLC25A15
9 cerebral creatine deficiency syndrome 10.1 OAT SLC6A8
10 deafness, autosomal recessive 16 10.1 LIG3 SLC25A15
11 cerebral creatine deficiency syndrome 2 10.1 OAT SLC6A8
12 argininosuccinic aciduria 10.0 ASS1 NAGS OTC
13 propionic acidemia 10.0 ASS1 NAGS OTC
14 hepatitis 10.0
15 hereditary spastic paraplegia 10.0
16 liver disease 10.0
17 paraplegia 10.0
18 inherited metabolic disorder 10.0
19 encephalopathy 10.0
20 reye syndrome 10.0 ASS1 OAT OTC
21 citrullinemia, classic 9.9 ASS1 NAGS OTC SLC25A15
22 carbamoyl phosphate synthetase i deficiency, hyperammonemia due to 9.9 ASS1 CPS1 NAGS OTC
23 histiocytosis-lymphadenopathy plus syndrome 9.9
24 argininemia 9.9 ASS1 CPS1 NAGS OTC
25 ornithine transcarbamylase deficiency, hyperammonemia due to 9.9 ASS1 CPS1 NAGS OTC
26 carbonic anhydrase va deficiency, hyperammonemia due to 9.8 ASS1 CPS1 NAGS OTC SLC25A15
27 alopecia universalis congenita 9.8
28 alopecia 9.8
29 amino acid metabolic disorder 9.7 MMD SLC6A8

Graphical network of the top 20 diseases related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:



Diseases related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Symptoms & Phenotypes for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Human phenotypes related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

60 33 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
2 chorioretinal atrophy 60 33 very rare (1%) Very rare (<4-1%) HP:0000533
3 failure to thrive 60 33 Frequent (79-30%) HP:0001508
4 clonus 60 33 Frequent (79-30%) HP:0002169
5 abnormal pyramidal sign 60 33 Frequent (79-30%) HP:0007256
6 hepatomegaly 60 33 Frequent (79-30%) HP:0002240
7 decreased liver function 60 33 Frequent (79-30%) HP:0001410
8 generalized myoclonic seizures 60 33 Occasional (29-5%) HP:0002123
9 specific learning disability 60 33 Frequent (79-30%) HP:0001328
10 cerebral cortical atrophy 60 33 Frequent (79-30%) HP:0002120
11 confusion 60 33 Frequent (79-30%) HP:0001289
12 coma 60 33 Occasional (29-5%) HP:0001259
13 hyperammonemia 60 33 Very frequent (99-80%) HP:0001987
14 lethargy 60 33 Frequent (79-30%) HP:0001254
15 generalized hypotonia 60 33 Frequent (79-30%) HP:0001290
16 poor coordination 60 33 Frequent (79-30%) HP:0002370
17 impaired vibratory sensation 60 33 Frequent (79-30%) HP:0002495
18 hyperornithinemia 60 33 Very frequent (99-80%) HP:0012026
19 protein avoidance 60 33 Frequent (79-30%) HP:0002038
20 episodic vomiting 60 33 Frequent (79-30%) HP:0002572
21 acute encephalopathy 60 33 Frequent (79-30%) HP:0006846
22 seizures 60 Occasional (29-5%)
23 hyperreflexia 60 Very frequent (99-80%)
24 global developmental delay 33 HP:0001263
25 cognitive impairment 60 Very frequent (99-80%)
26 hepatitis 60 Frequent (79-30%)
27 feeding difficulties 60 Frequent (79-30%)
28 decreased nerve conduction velocity 33 HP:0000762
29 elevated hepatic transaminase 60 Frequent (79-30%)
30 neurodevelopmental delay 60 Very frequent (99-80%)
31 hepatic failure 60 Very rare (<4-1%)
32 acute hepatitis 33 HP:0200119
33 progressive cerebellar ataxia 60 Frequent (79-30%)
34 hypopigmentation of the fundus 33 HP:0007894
35 spastic paraplegia 60 Frequent (79-30%)
36 spastic gait 60 Occasional (29-5%)
37 oroticaciduria 60 Frequent (79-30%)
38 tachypnea 60 Frequent (79-30%)
39 abnormality of the coagulation cascade 60 Occasional (29-5%)
40 abnormality of citrulline metabolism 60 Very frequent (99-80%)
41 speech apraxia 60 Frequent (79-30%)
42 respiratory alkalosis 60 Occasional (29-5%)
43 multifocal cerebral white matter abnormalities 60 Occasional (29-5%)
44 chorioretinal hypopigmentation 60 Very rare (<4-1%)
45 spastic paraparesis 33 HP:0002313
46 morphological abnormality of the pyramidal tract 33 HP:0002062
47 psychomotor retardation 33 HP:0025356

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
clonus
coma
more
Abdomen Liver:
hepatomegaly
acute hepatitis
liver dysfunction

Abdomen Gastrointestinal:
protein avoidance
episodic vomiting

Hematology:
coagulopathy due to liver dysfunction

Growth Other:
failure to thrive

Laboratory Abnormalities:
hyperammonemia
hyperornithinemia
homocitrullinuria

Neurologic Peripheral Nervous System:
decreased vibration sense (rare)

Clinical features from OMIM:

238970

UMLS symptoms related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:


seizures, clonus, lethargy, muscle spasticity, abnormal pyramidal signs, paraparesis, spastic

Drugs & Therapeutics for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Search Clinical Trials , NIH Clinical Center for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Genetic Tests for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Genetic tests related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

# Genetic test Affiliating Genes
1 Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome 30 SLC25A15

Anatomical Context for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

MalaCards organs/tissues related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

42
Liver, Testes, Brain, Cerebellum, Retina

Publications for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Articles related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

(show all 47)
# Title Authors Year
1
Hereditary Spastic Paraplegia Is a Common Phenotypic Finding in ARG1 Deficiency, P5CS Deficiency and HHH Syndrome: Three Inborn Errors of Metabolism Caused by Alteration of an Interconnected Pathway of Glutamate and Urea Cycle Metabolism. ( 30853934 )
2019
2
Lactate/pyruvate in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 30058227 )
2018
3
Late onset hyperornithinemia-hyperammonemia-homocitrullinuria syndrome - how web searching by the family solved unexplained unconsciousness: a case report. ( 30243302 )
2018
4
Milder Form of Urea Cycle Defect Revisited: Report and Review of Hyperornithinaemia-Hyperammonaemia-Homocitrullinuria (HHH) Syndrome Diagnosed in a Teenage Girl Presenting with Recurrent Encephalopathy. ( 28062886 )
2016
5
Heterologous Expression in Yeast of Human Ornithine Carriers ORNT1 and ORNT2 and of ORNT1 Alleles Implicated in HHH Syndrome in Humans. ( 26589310 )
2016
6
Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome. ( 27161368 )
2016
7
Ocular manifestations in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: a rare association. ( 25411929 )
2015
8
The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 25874378 )
2015
9
Ornithine In Vivo Administration Disrupts Redox Homeostasis and Decreases Synaptic Na(+), K (+)-ATPase Activity in Cerebellum of Adolescent Rats: Implications for the Pathogenesis of Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome. ( 25772141 )
2015
10
A novel mutation in the SLC25A15 gene in a Turkish patient with HHH syndrome: functional analysis of the mutant protein. ( 24721342 )
2014
11
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome in adulthood: a rare recognizable condition. ( 23247599 )
2013
12
Disturbance of redox homeostasis by ornithine and homocitrulline in rat cerebellum: a possible mechanism of cerebellar dysfunction in HHH syndrome. ( 23806752 )
2013
13
Impairment of brain redox homeostasis caused by the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome in vivo. ( 22798168 )
2012
14
Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1. ( 22292090 )
2012
15
Long-term follow-up of four patients affected by HHH syndrome. ( 22465082 )
2012
16
Dual mechanism of brain damage induced in vivo by the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 21059345 )
2011
17
Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan. ( 20574716 )
2010
18
Evidence that the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome induce oxidative stress in brain of young rats. ( 19683047 )
2009
19
Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study. ( 19242930 )
2009
20
The human and mouse SLC25A29 mitochondrial transporters rescue the deficient ornithine metabolism in fibroblasts of patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. ( 19287344 )
2009
21
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis. ( 17825324 )
2008
22
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure. ( 18376250 )
2008
23
A novel R275X mutation of the SLC25A15 gene in a Japanese patient with the HHH syndrome. ( 16376511 )
2006
24
HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation. ( 16601889 )
2006
25
Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. ( 16940241 )
2006
26
Determination of homocitrulline in urine of patients with HHH syndrome by liquid chromatography tandem mass spectrometry. ( 17053917 )
2006
27
Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. ( 12948741 )
2003
28
A novel mutation, P126R, in a Japanese patient with HHH syndrome. ( 11814739 )
2002
29
Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 11552031 )
2001
30
Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X. ( 11355015 )
2001
31
HHH syndrome associated with callosal agenesis and disordered neuronal migration. ( 11409836 )
2001
32
Conscientious metabolic monitoring on a patient with hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome undergoing anaesthesia. ( 11764411 )
2001
33
[Molecular genetic studies of mitochondrial ornithine transporter deficiency (HHH syndrome)]. ( 11712419 )
2001
34
Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. ( 10369256 )
1999
35
Neonatal onset of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with favorable outcome. ( 9329423 )
1997
36
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome. Ultrastructural changes of mitochondria in cultured dermal fibroblasts of three patients. ( 8739474 )
1996
37
Prenatal exclusion of the HHH syndrome. ( 7644438 )
1995
38
Ciliated cultured dermal fibroblasts in a patient with hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome. ( 8838382 )
1995
39
Neonatal form of the hyperornithinaemia, hyperammonaemia, and homocitrullinuria (HHH) syndrome and prenatal diagnosis. ( 1438066 )
1992
40
Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome: presentation as acute liver disease with coagulopathy. ( 1469525 )
1992
41
Abnormal urinary excretion of polyamines in HHH syndrome (hyperornithinemia associated with hyperammonemia and homocitrullinuria). ( 2288388 )
1990
42
Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 3407856 )
1988
43
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: low creatine excretion and effect of citrulline, arginine, or ornithine supplement. ( 3116497 )
1987
44
The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: an ornithine transport defect remediable with ornithine supplements. ( 3652557 )
1987
45
Studies on a case of HHH-syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria). ( 3960284 )
1986
46
Ornithine loading did not prevent induced hyperammonemia in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. ( 4080446 )
1985
47
Ultrastructural changes in fibroblast mitochondria of a patient with HHH-syndrome. ( 6441860 )
1984

Variations for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

76 (show all 14)
# Symbol AA change Variation ID SNP ID
1 SLC25A15 p.Gly27Glu VAR_012757 rs120899402
2 SLC25A15 p.Gly27Arg VAR_012758 rs104894430
3 SLC25A15 p.Pro126Arg VAR_012759
4 SLC25A15 p.Glu180Lys VAR_012760 rs104894424
5 SLC25A15 p.Gly190Asp VAR_012762 rs202247804
6 SLC25A15 p.Arg275Gln VAR_012764 rs104894431
7 SLC25A15 p.Met37Arg VAR_058948 rs121908533
8 SLC25A15 p.Leu71Gln VAR_058950 rs121908534
9 SLC25A15 p.Gly113Cys VAR_058951 rs199894905
10 SLC25A15 p.Phe188Leu VAR_058952 rs141028076
11 SLC25A15 p.Gly216Ser VAR_058953 rs141716760
12 SLC25A15 p.Thr272Ile VAR_058954 rs121908535
13 SLC25A15 p.Met273Lys VAR_058955 rs202247808
14 SLC25A15 p.Leu283Phe VAR_058956 rs202247809

ClinVar genetic disease variations for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome:

6 (show top 50) (show all 158)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A15 NM_014252.3(SLC25A15): c.562_564delTTC (p.Phe188del) deletion Pathogenic rs202247803 GRCh37 Chromosome 13, 41381539: 41381541
2 SLC25A15 NM_014252.3(SLC25A15): c.562_564delTTC (p.Phe188del) deletion Pathogenic rs202247803 GRCh38 Chromosome 13, 40807403: 40807405
3 SLC25A15 NM_014252.3(SLC25A15): c.538G> A (p.Glu180Lys) single nucleotide variant Pathogenic rs104894424 GRCh37 Chromosome 13, 41381515: 41381515
4 SLC25A15 NM_014252.3(SLC25A15): c.538G> A (p.Glu180Lys) single nucleotide variant Pathogenic rs104894424 GRCh38 Chromosome 13, 40807379: 40807379
5 SLC25A15 NM_014252.3(SLC25A15): c.535C> T (p.Arg179Ter) single nucleotide variant Pathogenic rs104894429 GRCh37 Chromosome 13, 41381512: 41381512
6 SLC25A15 NM_014252.3(SLC25A15): c.535C> T (p.Arg179Ter) single nucleotide variant Pathogenic rs104894429 GRCh38 Chromosome 13, 40807376: 40807376
7 SLC25A15 NM_014252.3(SLC25A15): c.79G> A (p.Gly27Arg) single nucleotide variant Pathogenic rs104894430 GRCh37 Chromosome 13, 41373216: 41373216
8 SLC25A15 NM_014252.3(SLC25A15): c.79G> A (p.Gly27Arg) single nucleotide variant Pathogenic rs104894430 GRCh38 Chromosome 13, 40799080: 40799080
9 SLC25A15 NM_014252.3(SLC25A15): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894431 GRCh37 Chromosome 13, 41383721: 41383721
10 SLC25A15 NM_014252.3(SLC25A15): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894431 GRCh38 Chromosome 13, 40809585: 40809585
11 SLC25A15 NM_014252.3(SLC25A15): c.110T> G (p.Met37Arg) single nucleotide variant Pathogenic rs121908533 GRCh37 Chromosome 13, 41373247: 41373247
12 SLC25A15 NM_014252.3(SLC25A15): c.110T> G (p.Met37Arg) single nucleotide variant Pathogenic rs121908533 GRCh38 Chromosome 13, 40799111: 40799111
13 SLC25A15 NM_014252.3(SLC25A15): c.212T> A (p.Leu71Gln) single nucleotide variant Pathogenic rs121908534 GRCh37 Chromosome 13, 41373349: 41373349
14 SLC25A15 NM_014252.3(SLC25A15): c.212T> A (p.Leu71Gln) single nucleotide variant Pathogenic rs121908534 GRCh38 Chromosome 13, 40799213: 40799213
15 SLC25A15 NM_014252.3(SLC25A15): c.815C> T (p.Thr272Ile) single nucleotide variant Pathogenic rs121908535 GRCh37 Chromosome 13, 41383712: 41383712
16 SLC25A15 NM_014252.3(SLC25A15): c.815C> T (p.Thr272Ile) single nucleotide variant Pathogenic rs121908535 GRCh38 Chromosome 13, 40809576: 40809576
17 SLC25A15 NM_014252.3(SLC25A15): c.95C> G (p.Thr32Arg) single nucleotide variant Pathogenic rs121908536 GRCh37 Chromosome 13, 41373232: 41373232
18 SLC25A15 NM_014252.3(SLC25A15): c.95C> G (p.Thr32Arg) single nucleotide variant Pathogenic rs121908536 GRCh38 Chromosome 13, 40799096: 40799096
19 SLC25A15 NM_014252.3(SLC25A15): c.337G> T (p.Gly113Cys) single nucleotide variant Pathogenic rs199894905 GRCh37 Chromosome 13, 41379276: 41379276
20 SLC25A15 NM_014252.3(SLC25A15): c.337G> T (p.Gly113Cys) single nucleotide variant Pathogenic rs199894905 GRCh38 Chromosome 13, 40805140: 40805140
21 SLC25A15 NM_014252.3(SLC25A15): c.44C> A (p.Ala15Glu) single nucleotide variant Pathogenic rs202247806 GRCh37 Chromosome 13, 41367406: 41367406
22 SLC25A15 NM_014252.3(SLC25A15): c.44C> A (p.Ala15Glu) single nucleotide variant Pathogenic rs202247806 GRCh38 Chromosome 13, 40793270: 40793270
23 SLC25A15 NM_014252.3(SLC25A15): c.564C> G (p.Phe188Leu) single nucleotide variant Pathogenic rs141028076 GRCh37 Chromosome 13, 41381541: 41381541
24 SLC25A15 NM_014252.3(SLC25A15): c.564C> G (p.Phe188Leu) single nucleotide variant Pathogenic rs141028076 GRCh38 Chromosome 13, 40807405: 40807405
25 SLC25A15 NM_014252.3(SLC25A15): c.569G> A (p.Gly190Asp) single nucleotide variant Pathogenic rs202247804 GRCh37 Chromosome 13, 41381546: 41381546
26 SLC25A15 NM_014252.3(SLC25A15): c.569G> A (p.Gly190Asp) single nucleotide variant Pathogenic rs202247804 GRCh38 Chromosome 13, 40807410: 40807410
27 SLC25A15 NM_014252.3(SLC25A15): c.658G> A (p.Gly220Arg) single nucleotide variant Pathogenic rs202247805 GRCh37 Chromosome 13, 41382609: 41382609
28 SLC25A15 NM_014252.3(SLC25A15): c.658G> A (p.Gly220Arg) single nucleotide variant Pathogenic rs202247805 GRCh38 Chromosome 13, 40808473: 40808473
29 SLC25A15 NM_014252.3(SLC25A15): c.818T> A (p.Met273Lys) single nucleotide variant Pathogenic rs202247808 GRCh37 Chromosome 13, 41383715: 41383715
30 SLC25A15 NM_014252.3(SLC25A15): c.818T> A (p.Met273Lys) single nucleotide variant Pathogenic rs202247808 GRCh38 Chromosome 13, 40809579: 40809579
31 SLC25A15 NM_014252.3(SLC25A15): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs202247807 GRCh37 Chromosome 13, 41383720: 41383720
32 SLC25A15 NM_014252.3(SLC25A15): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs202247807 GRCh38 Chromosome 13, 40809584: 40809584
33 SLC25A15 NM_014252.3(SLC25A15): c.847C> T (p.Leu283Phe) single nucleotide variant Pathogenic rs202247809 GRCh37 Chromosome 13, 41383744: 41383744
34 SLC25A15 NM_014252.3(SLC25A15): c.847C> T (p.Leu283Phe) single nucleotide variant Pathogenic rs202247809 GRCh38 Chromosome 13, 40809608: 40809608
35 SLC25A15 NM_014252.3(SLC25A15): c.117G> A (p.Thr39=) single nucleotide variant Benign/Likely benign rs41396747 GRCh37 Chromosome 13, 41373254: 41373254
36 SLC25A15 NM_014252.3(SLC25A15): c.117G> A (p.Thr39=) single nucleotide variant Benign/Likely benign rs41396747 GRCh38 Chromosome 13, 40799118: 40799118
37 SLC25A15 NM_014252.3(SLC25A15): c.333C> T (p.Ala111=) single nucleotide variant Benign/Likely benign rs9577152 GRCh37 Chromosome 13, 41379272: 41379272
38 SLC25A15 NM_014252.3(SLC25A15): c.333C> T (p.Ala111=) single nucleotide variant Benign/Likely benign rs9577152 GRCh38 Chromosome 13, 40805136: 40805136
39 SLC25A15 NM_014252.3(SLC25A15): c.760A> T (p.Ile254Leu) single nucleotide variant Benign rs17849654 GRCh37 Chromosome 13, 41382711: 41382711
40 SLC25A15 NM_014252.3(SLC25A15): c.760A> T (p.Ile254Leu) single nucleotide variant Benign rs17849654 GRCh38 Chromosome 13, 40808575: 40808575
41 SLC25A15 NM_014252.3(SLC25A15): c.182G> A (p.Arg61His) single nucleotide variant Conflicting interpretations of pathogenicity rs34615430 GRCh38 Chromosome 13, 40799183: 40799183
42 SLC25A15 NM_014252.3(SLC25A15): c.182G> A (p.Arg61His) single nucleotide variant Conflicting interpretations of pathogenicity rs34615430 GRCh37 Chromosome 13, 41373319: 41373319
43 SLC25A15 NM_014252.3(SLC25A15): c.-274T> C single nucleotide variant Benign rs7997189 GRCh37 Chromosome 13, 41363595: 41363595
44 SLC25A15 NM_014252.3(SLC25A15): c.-274T> C single nucleotide variant Benign rs7997189 GRCh38 Chromosome 13, 40789459: 40789459
45 SLC25A15 NM_014252.3(SLC25A15): c.-101C> G single nucleotide variant Uncertain significance rs886050239 GRCh37 Chromosome 13, 41363768: 41363768
46 SLC25A15 NM_014252.3(SLC25A15): c.-101C> G single nucleotide variant Uncertain significance rs886050239 GRCh38 Chromosome 13, 40789632: 40789632
47 SLC25A15 NM_014252.3(SLC25A15): c.225C> T (p.Ile75=) single nucleotide variant Conflicting interpretations of pathogenicity rs765380976 GRCh38 Chromosome 13, 40799226: 40799226
48 SLC25A15 NM_014252.3(SLC25A15): c.225C> T (p.Ile75=) single nucleotide variant Conflicting interpretations of pathogenicity rs765380976 GRCh37 Chromosome 13, 41373362: 41373362
49 SLC25A15 NM_014252.3(SLC25A15): c.*420T> G single nucleotide variant Likely benign rs75842883 GRCh38 Chromosome 13, 40810087: 40810087
50 SLC25A15 NM_014252.3(SLC25A15): c.*420T> G single nucleotide variant Likely benign rs75842883 GRCh37 Chromosome 13, 41384223: 41384223

Expression for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Search GEO for disease gene expression data for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome.

Pathways for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Pathways related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 ALDH18A1 ASS1 CPS1 NAGS OAT OTC
2
Show member pathways
13.38 ALDH18A1 ASS1 CPS1 NAGS OAT OTC
3
Show member pathways
11.98 ALDH18A1 ASS1 CPS1 NAGS OTC
4 11.51 ALDH18A1 ASS1 CPS1 OAT OTC
5
Show member pathways
11.05 ALDH18A1 OAT
6 10.96 ASS1 CPS1
7
Show member pathways
10.67 ASS1 CPS1 NAGS OTC
8
Show member pathways
10.48 ALDH18A1 ASS1 CPS1 NAGS OAT OTC
9
Show member pathways
10.37 ALDH18A1 OAT

GO Terms for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Cellular components related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.46 CPS1 NAGS OAT OTC
2 mitochondrial inner membrane GO:0005743 9.43 ALDH18A1 CPS1 OTC SLC25A15 SLC25A2 SLC25A29
3 mitochondrion GO:0005739 9.36 ALDH18A1 ASS1 CLIC1 CPS1 LIG3 NAGS

Biological processes related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 liver development GO:0001889 9.67 ASS1 CPS1 OTC
2 cellular amino acid biosynthetic process GO:0008652 9.62 ALDH18A1 ASS1 OAT OTC
3 response to zinc ion GO:0010043 9.61 ASS1 CPS1 OTC
4 response to amino acid GO:0043200 9.57 ASS1 CPS1
5 response to steroid hormone GO:0048545 9.56 ASS1 CPS1
6 cellular response to glucagon stimulus GO:0071377 9.55 ASS1 CPS1
7 glutamate metabolic process GO:0006536 9.54 ALDH18A1 NAGS
8 midgut development GO:0007494 9.54 ASS1 CPS1 OTC
9 response to growth hormone GO:0060416 9.52 ASS1 CPS1
10 response to amine GO:0014075 9.51 ASS1 CPS1
11 L-proline biosynthetic process GO:0055129 9.48 ALDH18A1 OAT
12 cellular response to oleic acid GO:0071400 9.46 ASS1 CPS1
13 citrulline biosynthetic process GO:0019240 9.43 ALDH18A1 CPS1 OTC
14 anion homeostasis GO:0055081 9.4 CPS1 OTC
15 mitochondrial L-ornithine transmembrane transport GO:1990575 9.33 SLC25A15 SLC25A2 SLC25A29
16 arginine biosynthetic process GO:0006526 9.26 ASS1 CPS1 NAGS OTC
17 urea cycle GO:0000050 9.1 ASS1 CPS1 NAGS OTC SLC25A15 SLC25A2

Molecular functions related to Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 9.33 ASS1 CPS1 LIG3
2 amino acid binding GO:0016597 8.96 ASS1 OTC
3 L-ornithine transmembrane transporter activity GO:0000064 8.62 SLC25A15 SLC25A2

Sources for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
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70 SNOMED-CT via HPO
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