HMGCLD
MCID: 3HY007
MIFTS: 51

3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency (HMGCLD)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

MalaCards integrated aliases for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

Name: 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency 57 20 43 58 72 36
Hydroxymethylglutaric Aciduria 57 73 20 43 58 72 70
Hmg-Coa Lyase Deficiency 57 73 20 43 58 72 13
Deficiency of Hydroxymethylglutaryl-Coa Lyase 43 29 6
Hl Deficiency 57 72 6
3-Hydroxy-3-Methylglutaric Aciduria 20 58
Hmg Coa Lyase Deficiency 20 70
Hmgcl Deficiency 57 72
Hmgcld 57 72
3-Hydroxy-3-Methylglutaryl-Coenzyme a Lyase Deficiency 43
3-Hydroxy 3-Methyl Glutaryl-Coa Lyase Deficiency 73
Hydroxymethylglutaryl-Coa Lyase Deficiency 39
3-Oh 3-Methyl Glutaric Aciduria 43
Hydroxymethylglutaricaciduria 72
Defect in Leucine Metabolism 20
3-Oh 3-Ch3 Glutaric Aciduria 43
Hepatic Lipase Deficiency 70
3hmg 43
Hmg 43

Characteristics:

Orphanet epidemiological data:

58
3-hydroxy-3-methylglutaric aciduria
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Portugal),<1/1000000 (United States),<1/1000000 (Taiwan, Province of China); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile,late childhood;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
triggers for acute decompensation include infections, vaccinations, and dietary changes
sensitivity to dietary leucine
variable features present during metabolic decompensation
long-term complications may include mental retardation, seizures, hypotonia, and spasticity


HPO:

31
3-hydroxy-3-methylglutaryl-coa lyase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course death in childhood


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

MedlinePlus Genetics : 43 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are compounds that are used for energy during periods without food (fasting).The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

MalaCards based summary : 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency, also known as hydroxymethylglutaric aciduria, is related to reye syndrome and 3-hydroxy-3-methylglutaryl-coa synthase-2 deficiency, and has symptoms including angina pectoris An important gene associated with 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency is HMGCL (3-Hydroxy-3-Methylglutaryl-CoA Lyase), and among its related pathways/superpathways are Valine, leucine and isoleucine degradation and Butanoate metabolism. Affiliated tissues include kidney, bone and heart, and related phenotypes are hyperammonemia and metabolic acidosis

GARD : 20 HMG CoA lyase deficiency is an inherited disorder in which the body cannot process a protein called leucine or make ketones. Ketones are used for energy during periods of fasting. The signs and symptoms of condition usually appear within the first year of life and include episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone ( hypotonia ). During an episode, blood sugar levels can become dangerously low ( hypoglycemia ), and a buildup of harmful compounds can cause the blood to become too acidic ( metabolic acidosis ). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress. Mutations in the HMGCL gene cause HMG-CoA lyase deficiency, and this condition is inherited in an autosomal recessive pattern. Treatment usually involves a team of specialists including a metabolics and/or genetics specialist and a dietician and may include avoidance of fasting, a low leucine diet, and supplementation with L-carnitine.

OMIM® : 57 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988). (246450) (Updated 20-May-2021)

KEGG : 36 3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a rare autosomal recessive genetic disorder characterized by recurrent episodes of metabolic acidosis, hyperammonemia without ketosis, hypoglycemia, lethargy, hepatomegaly, and seizures.

UniProtKB/Swiss-Prot : 72 3-hydroxy-3-methylglutaryl-CoA lyase deficiency: An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.

Wikipedia : 73 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is an uncommon inherited disorder in which the body... more...

Related Diseases for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Diseases related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 419)
# Related Disease Score Top Affiliating Genes
1 reye syndrome 30.0 HMGCLL1 HMGCL
2 3-hydroxy-3-methylglutaryl-coa synthase-2 deficiency 11.5
3 hepatic lipase deficiency 11.4
4 lipase deficiency, combined 11.3
5 necrotizing autoimmune myopathy 11.1
6 hmg coa synthetase deficiency 11.0
7 yemenite deaf-blind hypopigmentation syndrome 10.9
8 cerebrotendinous xanthomatosis 10.9
9 mevalonic aciduria 10.9
10 lathosterolosis 10.9
11 hypoglycemia 10.8
12 hypercholesterolemia, familial, 1 10.8
13 metabolic acidosis 10.7
14 carbonic anhydrase va deficiency, hyperammonemia due to 10.6
15 myopathy 10.5
16 autosomal recessive disease 10.5
17 metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 10.5
18 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.5
19 lipid metabolism disorder 10.5
20 ocular motor apraxia 10.4
21 coronary heart disease 1 10.4
22 ovarian hyperstimulation syndrome 10.4
23 isovaleric acidemia 10.4
24 retinitis pigmentosa 10.4
25 branchiootic syndrome 1 10.4
26 aphasia 10.4
27 neuroretinitis 10.4
28 leukodystrophy 10.4
29 facial paralysis 10.4
30 retinitis 10.4
31 brain edema 10.4
32 intracranial hypertension 10.4
33 encephalopathy 10.4
34 cerebral visual impairment 10.4
35 familial hypercholesterolemia 10.4
36 atrial standstill 1 10.4
37 organic acidemia 10.4
38 pre-eclampsia 10.4
39 vacterl association 10.4
40 epilepsy 10.4
41 acute pancreatitis 10.4
42 pancreatitis 10.4
43 inherited metabolic disorder 10.4
44 uniparental disomy of chromosome 1 10.4
45 infertility 10.4
46 familial hyperlipidemia 10.3
47 atherosclerosis susceptibility 10.3
48 lipoprotein quantitative trait locus 10.3
49 down syndrome 10.3
50 endocardial fibroelastosis 10.3

Graphical network of the top 20 diseases related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:



Diseases related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Symptoms & Phenotypes for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Human phenotypes related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

58 31 (show top 50) (show all 67)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperammonemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001987
2 metabolic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001942
3 nonketotic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001958
4 3-methylglutaric aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003344
5 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
6 anemia 58 31 frequent (33%) Frequent (79-30%) HP:0001903
7 hyperuricemia 58 31 frequent (33%) Frequent (79-30%) HP:0002149
8 elevated hepatic transaminase 58 31 frequent (33%) Frequent (79-30%) HP:0002910
9 anorexia 58 31 frequent (33%) Frequent (79-30%) HP:0002039
10 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
11 lethargy 58 31 frequent (33%) Frequent (79-30%) HP:0001254
12 prolonged prothrombin time 58 31 frequent (33%) Frequent (79-30%) HP:0008151
13 tachypnea 58 31 frequent (33%) Frequent (79-30%) HP:0002789
14 recurrent hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0001988
15 apathy 58 31 frequent (33%) Frequent (79-30%) HP:0000741
16 episodic vomiting 58 31 frequent (33%) Frequent (79-30%) HP:0002572
17 reye syndrome-like episodes 58 31 frequent (33%) Frequent (79-30%) HP:0006582
18 lipid accumulation in hepatocytes 58 31 frequent (33%) Frequent (79-30%) HP:0006561
19 seizure 31 frequent (33%) HP:0001250
20 hypotonia 31 frequent (33%) HP:0001252
21 hypotension 58 31 occasional (7.5%) Occasional (29-5%) HP:0002615
22 dehydration 58 31 occasional (7.5%) Occasional (29-5%) HP:0001944
23 fatigue 58 31 occasional (7.5%) Occasional (29-5%) HP:0012378
24 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
25 fever 58 31 occasional (7.5%) Occasional (29-5%) HP:0001945
26 intellectual disability, severe 58 31 occasional (7.5%) Occasional (29-5%) HP:0010864
27 myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001336
28 pallor 58 31 occasional (7.5%) Occasional (29-5%) HP:0000980
29 jaundice 58 31 occasional (7.5%) Occasional (29-5%) HP:0000952
30 intellectual disability, moderate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002342
31 apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002104
32 weight loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0001824
33 hyporeflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001265
34 encephalopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001298
35 diarrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002014
36 leukopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001882
37 edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0000969
38 leukocytosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001974
39 ketonuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002919
40 hypsarrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002521
41 thrombocytosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001894
42 ataxia 58 31 very rare (1%) Very rare (<4-1%) HP:0001251
43 dysarthria 58 31 very rare (1%) Very rare (<4-1%) HP:0001260
44 hypothermia 58 31 very rare (1%) Very rare (<4-1%) HP:0002045
45 microcephaly 58 31 very rare (1%) Very rare (<4-1%) HP:0000252
46 dilated cardiomyopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0001644
47 leukoencephalopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0002352
48 cardiac arrest 58 31 very rare (1%) Very rare (<4-1%) HP:0001695
49 hypoglycemic coma 58 31 very rare (1%) Very rare (<4-1%) HP:0001325
50 acute pancreatitis 58 31 very rare (1%) Very rare (<4-1%) HP:0001735

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
spasticity
myoclonus
abnormal eeg
coma (uncommon)
more
Abdomen Liver:
hepatomegaly

Hematology:
anemia
decreased prothrombin time

Neurologic Behavioral Psychiatric Manifestations:
somnolence
apathy/lethargy

Respiratory:
tachydyspnea
kussmal breathing

Skin Nails Hair Skin:
paleness

Muscle Soft Tissue:
muscular hypotonia

Laboratory Abnormalities:
hypoglycemia
hyperuricemia
hyperammonemia
acidosis
increased anion gap
more
Metabolic Features:
metabolic acidosis

Head And Neck Head:
microcephaly (in some patients)

Abdomen Gastrointestinal:
recurrent vomiting
refusal of nutrition

Clinical features from OMIM®:

246450 (Updated 20-May-2021)

UMLS symptoms related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:


angina pectoris

Drugs & Therapeutics for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Search Clinical Trials , NIH Clinical Center for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Genetic Tests for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Genetic tests related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

# Genetic test Affiliating Genes
1 Deficiency of Hydroxymethylglutaryl-Coa Lyase 29 HMGCL

Anatomical Context for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

MalaCards organs/tissues related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

40
Kidney, Bone, Heart, Lung, Liver, Thyroid, Brain

Publications for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Articles related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

(show top 50) (show all 94)
# Title Authors PMID Year
1
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: Clinical presentation and outcome in a series of 37 patients. 6 57
28583327 2017
2
Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency. 6 57
11129331 2000
3
HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q. 57 6
9463337 1998
4
3-Hydroxy-3-methylglutaryl CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. 6 57
8617516 1996
5
3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. 6 57
8440722 1993
6
Molecular analysis of Taiwanese patients with 3-hydroxy-3-methylglutaryl CoA lyase deficiency. 6 61
19036343 2009
7
Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi population. 61 6
17173698 2006
8
Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria. 61 6
16330550 2006
9
A nonsense mutation in the 3-hydroxy-3-methylglutaryl-CoA lyase gene produces exon skipping in two patients of different origin with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 61 6
9163320 1997
10
Modeling of a mutation responsible for human 3-hydroxy-3-methylglutaryl-CoA lyase deficiency implicates histidine 233 as an active site residue. 6 61
8798725 1996
11
Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. 6 61
7479590 1995
12
Sudden death in an infant with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 57 61
2246860 1990
13
Identification of 3-methylglutarylcarnitine. A new diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. 57 61
3958190 1986
14
3-Hydroxy-3-methylglutaryl-coenzyme a lyase deficiency: a review. 57 61
3099065 1986
15
A child with acute pancreatitis and recurrent hypoglycemia due to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 61 57
6489380 1984
16
3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: one disease - many faces. 6
32059735 2020
17
Successful Management of Pregnancies in Patients with Inherited Disorders of Ketone Body Metabolism. 6
28488182 2018
18
Analysis of aberrant splicing and nonsense-mediated decay of the stop codon mutations c.109G>T and c.504_505delCT in 7 patients with HMG-CoA lyase deficiency. 6
23465862 2013
19
Characterization of a novel HMG-CoA lyase enzyme with a dual location in endoplasmic reticulum and cytosol. 6
22847177 2012
20
[Late onset 3-HMG-CoA lyase deficiency: a rare but treatable disorder]. 6
19932602 2010
21
Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria. 6
19177531 2009
22
Molecular genetics of HMG-CoA lyase deficiency. 6
17692550 2007
23
3-Hydroxy-3-methylglutaryl coenzyme a lyase deficiency with reversible white matter changes after treatment. 6
17628222 2007
24
Skipping of exon 2 and exons 2 plus 3 of HMG-CoA lyase (HL) gene produces the loss of beta sheets 1 and 2 in the recently proposed (beta-alpha)8 TIM barrel model of HL. 6
15752612 2005
25
The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency. 6
15308132 2004
26
Evaluation of 3-hydroxy-3-methylglutaryl-coenzyme A lyase arginine-41 as a catalytic residue: use of acetyldithio-coenzyme A to monitor product enolization. 6
15122894 2004
27
Characterization of a novel mutation causing hepatic lipase deficiency among French Canadians. 6
12777476 2003
28
Biochemical and molecular analyses in three patients with 3-hydroxy-3-methylglutaric aciduria. 6
14518825 2003
29
3-Hydroxy-3-methylglutaric aciduria in an Italian patient is caused by a new nonsense mutation in the HMGCL gene. 6
11461194 2001
30
[3-hydroxy-3-methylglutaraciduria (case report of a female Turkish sisters with 3-hydroxy-3- methylglutaryl-Coenzyme A lyase deficiency]. 6
10916782 2000
31
3-Hydroxy-3-methylglutaryl-CoA lyase (HL): gene targeting causes prenatal lethality in HL-deficient mice. 57
9817922 1998
32
Two missense point mutations in different alleles in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene produce 3-hydroxy-3-methylglutaric aciduria in a French patient. 6
9784232 1998
33
A nonsense mutation in the exon 2 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing three mature mRNAs is the main cause of 3-hydroxy-3-methylglutaric aciduria in European Mediterranean patients. 6
9439591 1998
34
A two-base deletion in exon 6 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing the skipping of exons 5 and 6 determines 3-hydroxy-3-methylglutaric aciduria. 6
9392428 1997
35
Neurometabolic diseases at a national referral center: five years experience at the King Faisal Specialist Hospital and Research Centre. 57
1588014 1992
36
Compound heterozygosity for mutant hepatic lipase in familial hepatic lipase deficiency. 6
1883393 1991
37
A hepatic lipase gene mutation associated with heritable lipolytic deficiency. 6
1671786 1991
38
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency in Saudi Arabia. 57
1886403 1991
39
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations. 57
2116546 1990
40
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. 57
3063529 1988
41
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: report of five new patients. 57
3128690 1988
42
3-Hydroxy-3-methylglutaryl-CoA lyase in human skin fibroblasts: study of its properties and deficient activity in 3-hydroxy-3-methylglutaric aciduria patients using a simple spectrophotometric method. 57
2450702 1988
43
Genetic complementation analysis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency in cultured fibroblasts. 57
6475954 1984
44
3-Hydroxy-3-methylglutaryl coenzyme A lyase deficiency. Follow-up of first described case. 57
6112838 1981
45
Hydroxymethylglutaryl CoA lyase deficiency: features resembling Reye syndrome. 57
6156427 1980
46
3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency: postnatal management following prenatal diagnosis by analysis of maternal urine. 57
91680 1979
47
beta-Hydroxy-beta-methyglutaricaciduria presenting as Reye's syndrome. 57
85928 1979
48
Lethal hypoglycemia in a child with a deficiency of 3-hydroxy-3-methylglutarylcoenzyme A lyase. 57
758433 1979
49
3-Hydroxy-3-methylglutaric aciduria: 3-hydroxy-3-methylglutaryl-coenzyme A lyase levels in leucocytes. 57
1000856 1976
50
The urinary organic acid profile associated with 3-hydroxy-3-methylglutaric aciduria. 57
1000872 1976

Variations for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

ClinVar genetic disease variations for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

6 (show top 50) (show all 188)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LIPC NM_000236.3(LIPC):c.583G>A (p.Ala195Thr) SNV Pathogenic 29776 rs1566946168 GRCh37: 15:58837949-58837949
GRCh38: 15:58545750-58545750
2 LIPC NM_000236.3(LIPC):c.1014del (p.Arg338fs) Deletion Pathogenic 1034118 GRCh37: 15:58840733-58840733
GRCh38: 15:58548534-58548534
3 LIPC NM_000236.3(LIPC):c.456+2T>C SNV Pathogenic 1034119 GRCh37: 15:58834168-58834168
GRCh38: 15:58541969-58541969
4 LIPC NM_000236.3(LIPC):c.845C>A (p.Ser282Ter) SNV Pathogenic 1034120 GRCh37: 15:58840565-58840565
GRCh38: 15:58548366-58548366
5 HMGCL HMGCL, 930-BP DEL, EX3-6DEL Deletion Pathogenic 11956 GRCh37:
GRCh38:
6 HMGCL NM_000191.3(HMGCL):c.835G>A (p.Glu279Lys) SNV Pathogenic 11958 rs121964998 GRCh37: 1:24130931-24130931
GRCh38: 1:23804441-23804441
7 HMGCL NM_000191.3(HMGCL):c.914_915del (p.Phe305fs) Deletion Pathogenic 31084 rs786205431 GRCh37: 1:24129016-24129017
GRCh38: 1:23802526-23802527
8 HMGCL NM_000191.3(HMGCL):c.499T>A (p.Tyr167Asn) SNV Pathogenic 523024 rs1553132209 GRCh37: 1:24137288-24137288
GRCh38: 1:23810798-23810798
9 HMGCL NM_000191.3(HMGCL):c.31C>T (p.Arg11Ter) SNV Pathogenic 521752 rs1212444447 GRCh37: 1:24151875-24151875
GRCh38: 1:23825385-23825385
10 HMGCL NM_000191.3(HMGCL):c.503_504TC[1] (p.Ser169fs) Microsatellite Pathogenic 521753 rs764264834 GRCh37: 1:24137281-24137282
GRCh38: 1:23810791-23810792
11 HMGCL NM_000191.3(HMGCL):c.27del (p.Arg10fs) Deletion Pathogenic 557324 rs1409716731 GRCh37: 1:24151879-24151879
GRCh38: 1:23825389-23825389
12 HMGCL NM_000191.3(HMGCL):c.876+1G>C SNV Pathogenic 930617 GRCh37: 1:24130889-24130889
GRCh38: 1:23804399-23804399
13 HMGCL NM_000191.3(HMGCL):c.374_375del (p.Val125fs) Deletion Pathogenic 945139 GRCh37: 1:24140802-24140803
GRCh38: 1:23814312-23814313
14 HMGCL NM_000191.3(HMGCL):c.865_866del (p.Gly289fs) Deletion Pathogenic 1032247 GRCh37: 1:24130900-24130901
GRCh38: 1:23804410-23804411
15 HMGCL NM_000191.3(HMGCL):c.122G>A (p.Arg41Gln) SNV Pathogenic 11957 rs121964997 GRCh37: 1:24147022-24147022
GRCh38: 1:23820532-23820532
16 HMGCL NM_000191.3(HMGCL):c.109G>T (p.Glu37Ter) SNV Pathogenic 195033 rs763494292 GRCh37: 1:24147035-24147035
GRCh38: 1:23820545-23820545
17 HMGCL NM_000191.3(HMGCL):c.202_203CT[2] (p.Ser69fs) Microsatellite Pathogenic/Likely pathogenic 11954 rs752137615 GRCh37: 1:24144011-24144012
GRCh38: 1:23817521-23817522
18 HMGCL NM_000191.3(HMGCL):c.698A>G (p.His233Arg) SNV Pathogenic/Likely pathogenic 167180 rs727503963 GRCh37: 1:24134677-24134677
GRCh38: 1:23808187-23808187
19 HMGCL NM_000191.3(HMGCL):c.718C>T (p.Gln240Ter) SNV Likely pathogenic 984174 GRCh37: 1:24134657-24134657
GRCh38: 1:23808167-23808167
20 HMGCL NM_000191.3(HMGCL):c.714T>G (p.Tyr238Ter) SNV Likely pathogenic 984175 GRCh37: 1:24134661-24134661
GRCh38: 1:23808171-23808171
21 HMGCL NM_000191.3(HMGCL):c.594C>G (p.Tyr198Ter) SNV Likely pathogenic 984176 GRCh37: 1:24134781-24134781
GRCh38: 1:23808291-23808291
22 HMGCL NM_000191.3(HMGCL):c.331A>T (p.Lys111Ter) SNV Likely pathogenic 984177 GRCh37: 1:24143182-24143182
GRCh38: 1:23816692-23816692
23 HMGCL NM_000191.3(HMGCL):c.275T>A (p.Leu92Ter) SNV Likely pathogenic 984178 GRCh37: 1:24143238-24143238
GRCh38: 1:23816748-23816748
24 HMGCL NM_000191.3(HMGCL):c.137dup (p.Asn46fs) Duplication Likely pathogenic 853456 GRCh37: 1:24147006-24147007
GRCh38: 1:23820516-23820517
25 HMGCL NM_000191.3(HMGCL):c.528T>A (p.Tyr176Ter) SNV Likely pathogenic 557442 rs112508527 GRCh37: 1:24137259-24137259
GRCh38: 1:23810769-23810769
26 HMGCL NM_000191.3(HMGCL):c.286C>T (p.Gln96Ter) SNV Likely pathogenic 557482 rs890995574 GRCh37: 1:24143227-24143227
GRCh38: 1:23816737-23816737
27 HMGCL NM_000191.3(HMGCL):c.413del (p.Asn138fs) Deletion Likely pathogenic 556138 rs1553132520 GRCh37: 1:24140764-24140764
GRCh38: 1:23814274-23814274
28 HMGCL NM_000191.3(HMGCL):c.562-2A>G SNV Likely pathogenic 556274 rs1553131955 GRCh37: 1:24134815-24134815
GRCh38: 1:23808325-23808325
29 HMGCL NM_000191.3(HMGCL):c.501C>G (p.Tyr167Ter) SNV Likely pathogenic 556313 rs200189529 GRCh37: 1:24137286-24137286
GRCh38: 1:23810796-23810796
30 HMGCL NM_000191.3(HMGCL):c.121dup (p.Arg41fs) Duplication Likely pathogenic 556351 rs1553133042 GRCh37: 1:24147022-24147023
GRCh38: 1:23820532-23820533
31 HMGCL NM_000191.3(HMGCL):c.60+1G>T SNV Likely pathogenic 555710 rs1324641233 GRCh37: 1:24151845-24151845
GRCh38: 1:23825355-23825355
32 HMGCL NM_000191.3(HMGCL):c.121C>T (p.Arg41Ter) SNV Likely pathogenic 553933 rs770225915 GRCh37: 1:24147023-24147023
GRCh38: 1:23820533-23820533
33 HMGCL NM_000191.3(HMGCL):c.286del (p.Gln96fs) Deletion Likely pathogenic 554439 rs1184002840 GRCh37: 1:24143227-24143227
GRCh38: 1:23816737-23816737
34 HMGCL NM_000191.3(HMGCL):c.3G>T (p.Met1Ile) SNV Likely pathogenic 554719 rs1302190999 GRCh37: 1:24151903-24151903
GRCh38: 1:23825413-23825413
35 HMGCL NM_000191.3(HMGCL):c.528T>G (p.Tyr176Ter) SNV Likely pathogenic 554809 rs112508527 GRCh37: 1:24137259-24137259
GRCh38: 1:23810769-23810769
36 HMGCL NM_000191.3(HMGCL):c.804C>A (p.Tyr268Ter) SNV Likely pathogenic 552412 rs765198174 GRCh37: 1:24130962-24130962
GRCh38: 1:23804472-23804472
37 HMGCL NM_000191.3(HMGCL):c.863T>A (p.Leu288Ter) SNV Likely pathogenic 552798 rs1425615804 GRCh37: 1:24130903-24130903
GRCh38: 1:23804413-23804413
38 LIPC NM_000236.3(LIPC):c.738_739dup (p.Gly247fs) Duplication Conflicting interpretations of pathogenicity 631739 rs749932377 GRCh37: 15:58838103-58838104
GRCh38: 15:58545904-58545905
39 HMGCL NM_000191.3(HMGCL):c.853del (p.Met284_Leu285insTer) Deletion Conflicting interpretations of pathogenicity 632104 rs779339230 GRCh37: 1:24130913-24130913
GRCh38: 1:23804423-23804423
40 HMGCL NM_000191.3(HMGCL):c.493C>T (p.Arg165Trp) SNV Conflicting interpretations of pathogenicity 558583 rs764039230 GRCh37: 1:24140684-24140684
GRCh38: 1:23814194-23814194
41 HMGCL NM_000191.3(HMGCL):c.454G>A (p.Ala152Thr) SNV Conflicting interpretations of pathogenicity 766092 rs146306707 GRCh37: 1:24140723-24140723
GRCh38: 1:23814233-23814233
42 HMGCL NM_000191.3(HMGCL):c.501C>T (p.Tyr167=) SNV Conflicting interpretations of pathogenicity 767617 rs200189529 GRCh37: 1:24137286-24137286
GRCh38: 1:23810796-23810796
43 HMGCL NM_000191.3(HMGCL):c.594C>T (p.Tyr198=) SNV Conflicting interpretations of pathogenicity 296852 rs139799938 GRCh37: 1:24134781-24134781
GRCh38: 1:23808291-23808291
44 HMGCL NM_000191.3(HMGCL):c.470C>T (p.Ala157Val) SNV Uncertain significance 652537 rs147752765 GRCh37: 1:24140707-24140707
GRCh38: 1:23814217-23814217
45 HMGCL NM_000191.3(HMGCL):c.76A>T (p.Met26Leu) SNV Uncertain significance 1040599 GRCh37: 1:24147068-24147068
GRCh38: 1:23820578-23820578
46 HMGCL NM_000191.3(HMGCL):c.386C>G (p.Ala129Gly) SNV Uncertain significance 1058927 GRCh37: 1:24140791-24140791
GRCh38: 1:23814301-23814301
47 HMGCL NM_000191.3(HMGCL):c.814G>T (p.Ala272Ser) SNV Uncertain significance 1061122 GRCh37: 1:24130952-24130952
GRCh38: 1:23804462-23804462
48 HMGCL NM_000191.3(HMGCL):c.244G>A (p.Val82Ile) SNV Uncertain significance 449273 rs538620811 GRCh37: 1:24143974-24143974
GRCh38: 1:23817484-23817484
49 LIPC NM_000236.3(LIPC):c.1214C>T (p.Thr405Met) SNV Uncertain significance 14451 rs113298164 GRCh37: 15:58855748-58855748
GRCh38: 15:58563549-58563549
50 HMGCL NM_000191.3(HMGCL):c.497+3G>A SNV Uncertain significance 296853 rs763178392 GRCh37: 1:24140677-24140677
GRCh38: 1:23814187-23814187

UniProtKB/Swiss-Prot genetic disease variations for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency:

72 (show all 19)
# Symbol AA change Variation ID SNP ID
1 HMGCL p.Arg41Gln VAR_003744 rs121964997
2 HMGCL p.Asp42Glu VAR_003745
3 HMGCL p.Asp42Gly VAR_003746 rs146790261
4 HMGCL p.Asp42His VAR_003747
5 HMGCL p.Val70Leu VAR_003748 rs121964996
6 HMGCL p.His233Arg VAR_003749 rs727503963
7 HMGCL p.Glu279Lys VAR_014202 rs121964998
8 HMGCL p.Glu37Lys VAR_058440
9 HMGCL p.Lys48Asn VAR_058441
10 HMGCL p.Ser75Arg VAR_058442 rs135794206
11 HMGCL p.Ser142Phe VAR_058443
12 HMGCL p.Cys174Tyr VAR_058444 rs765475941
13 HMGCL p.Phe192Ser VAR_058445
14 HMGCL p.Ile200Phe VAR_058446
15 HMGCL p.Ser201Tyr VAR_058447 rs760106433
16 HMGCL p.Gly203Glu VAR_058448 rs155313194
17 HMGCL p.Asp204Asn VAR_058449
18 HMGCL p.Leu263Pro VAR_058450
19 HMGCL p.Arg165Gln VAR_065453 rs199587895

Expression for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Search GEO for disease gene expression data for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency.

Pathways for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Pathways related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280
2 Butanoate metabolism hsa00650

GO Terms for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

Cellular components related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 8.62 HMGCL BDH1

Biological processes related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.33 LIPC HMGCLL1 HMGCL
2 leucine catabolic process GO:0006552 8.96 HMGCLL1 HMGCL
3 ketone body biosynthetic process GO:0046951 8.8 HMGCLL1 HMGCL BDH1

Molecular functions related to 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.33 HMGCLL1 HMGCL BDH1
2 lyase activity GO:0016829 9.26 HMGCLL1 HMGCL
3 oxo-acid-lyase activity GO:0016833 8.96 HMGCLL1 HMGCL
4 hydroxymethylglutaryl-CoA lyase activity GO:0004419 8.62 HMGCLL1 HMGCL

Sources for 3-Hydroxy-3-Methylglutaryl-Coa Lyase Deficiency

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....