HLCS DEFICIENCY
MCID: HLC001
MIFTS: 48

Holocarboxylase Synthetase Deficiency (HLCS DEFICIENCY)

Categories: Genetic diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Holocarboxylase Synthetase Deficiency

MalaCards integrated aliases for Holocarboxylase Synthetase Deficiency:

Name: Holocarboxylase Synthetase Deficiency 57 12 74 20 43 58 73 36 29 13 54 6 44 15 39 71
Early-Onset Multiple Carboxylase Deficiency 20 58 73
Hlcs Deficiency 57 43 73
Neonatal Multiple Carboxylase Deficiency 20 58
Biotin- Ligase Deficiency 12 43
Early-Onset Biotin-Responsive Multiple Carboxylase Deficiency 43
Biotin-Responsive Multiple Carboxylase Deficiencies 29
Biotin-Responsive Multiple Carboxylase Deficiency 73
Multiple Carboxylase Deficiency - Neonatal Onset 12
Multiple Carboxylase Deficiency, Neonatal Form 57
Multiple Carboxylase Deficiency, Early Onset 57
Early-Onset Combined Carboxylase Deficiency 43
Infantile Multiple Carboxylase Deficiency 43
Biotin-Responsive Mcd 73
Mcd Neonatal Form 73
Early-Onset Mcd 73

Characteristics:

Orphanet epidemiological data:

58
holocarboxylase synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
age of onset - birth to 15 months


HPO:

31
holocarboxylase synthetase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases
Inborn errors of metabolism


Summaries for Holocarboxylase Synthetase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79242DefinitionA life-threatening early-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism, that, if untreated, is characterized by vomiting, tachypnea, irritability, lethargy, exfoliative dermatitis, and seizures that can worsen to coma.EpidemiologyThe exact prevalence of HCSD is unknown, but the condition is one of the rarest inborn errors of metabolism. Annual incidence is estimated to be less than 1/200,000 live births.Clinical descriptionClinical onset is usually within hours, days or weeks of birth. Individuals with the disorder usually exhibit poor appetite, vomiting, lethargy, irritability, hypotonia and exfoliative dermatitis. Metabolically, they have ketolactic acidosis, organic acidemia (-uria) and hyperammonemia. Without treatment, affected infants may progress to intractable seizures, cerebral edema and coma. These children often develop growth and developmental delays.EtiologyHolocarboxylase synthetase deficiency is caused by mutations in the HLCS gene (21q22.1) resulting in reduced HCS activity. This enzyme is important in covalent binding of biotin to the various biotin-dependent carboxylases that require the vitamin for activity. Failure to attach the biotin results in multiple carboxylase deficiency and accumulation of various, specific abnormal organic acids.Diagnostic methodsSome affected individuals are identified through newborn screening by demonstration of abnormal organic acids, consistent with multiple carboxyalse deficiency. Diagnosis is based on clinical signs and typical organic acid abnormalities. Confirmational testing can be performed by demonstrating deficient HCS activity in leukocytes or fibroblast extracts or by mutation analysis.Differential diagnosisConditions to be considered in the differential diagnosis based on organic acids include biotinidase deficiency (see this term) and isolated carboxyalse deficiencies; based on hyperammonemia, include urea cycle defects (see this term); and based on neurological compromise and seizures in the neonatal period, include sepsis and other inborn errors of metabolism.Antenatal diagnosisPrenatal diagnosis can be performed by organic acid analysis by stable isotope dilution techniques in amniotic fluid, enzymatic determination of HCS activity in amniocytes, or mutation analysis on DNA from chorionic villus biopsy or amniocentesis.Genetic counselingHCS deficiency is inherited as an autosomal recessive trait. Genetic counseling is available to families who have children with the disorder. Siblings of affected children are unlikely to have the disorder or they would have developed symptoms, but they may be carriers.Management and treatmentThe primary treatment for HCS deficiency is free biotin supplementation which can improve the clinical status of symptomatic individuals with the enzyme deficiency and prevent some or all symptoms from developing in asymptomatic individuals with the disorder. Treatment should be started as soon as possible after diagnosis and must be continued lifelong. Affected individuals should be monitored for later-onset complications and for compliance with therapy. Timely and ongoing treatment makes it possible to reduce symptoms considerably, although some patients develop complications despite appropriate treatment often requiring higher doses of biotin.PrognosisIn the absence of early diagnosis and treatment, mortality is high. Morbidity in surviving affected individuals depends on the time of diagnosis and on the degree of damage related to metabolic crises.Visit the Orphanet disease page for more resources.

MalaCards based summary : Holocarboxylase Synthetase Deficiency, also known as early-onset multiple carboxylase deficiency, is related to multiple carboxylase deficiency and biotin deficiency, and has symptoms including seizures, vomiting and lethargy. An important gene associated with Holocarboxylase Synthetase Deficiency is HLCS (Holocarboxylase Synthetase), and among its related pathways/superpathways are Biotin metabolism and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include liver and skin, and related phenotypes are nausea and vomiting and growth delay

Disease Ontology : 12 A multiple carboxylase deficiency that involves a deficiency in holocarboxylase synthetase.

MedlinePlus Genetics : 43 Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, which is a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.

OMIM® : 57 Holocarboxylase synthetase deficiency, a biotin-responsive multiple carboxylase deficiency (MCD), is characterized by metabolic acidosis, lethargy, hypotonia, convulsions, and dermatitis. Most patients present in the newborn or early infantile period, but some become symptomatic in the later infantile period (summary by Suzuki et al., 2005). Also see biotinidase deficiency (253260), another form of MCD with a later onset. Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981). (253270) (Updated 05-Mar-2021)

KEGG : 36 Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder of biotin metabolism that results from holocarboxylase synthetase activity disruption. HLCS deficiency is also called multiple carboxylase deficiency, because deficient HLCS activity results in reduced activity of multiple carboxylases. In humans, four carboxylases are known to be biotinylated by HLCS. They are pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase. Symptoms of HLCS deficiency include metabolic acidosis, a characteristic organic aciduria, lethargy, hypotonia, convulsions, and dermatitis.

UniProtKB/Swiss-Prot : 73 Holocarboxylase synthetase deficiency: A neonatal form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. In holocarboxylase synthetase deficiency, clinical and biochemical symptoms improve dramatically with administration of biotin.

Wikipedia : 74 Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to... more...

Related Diseases for Holocarboxylase Synthetase Deficiency

Diseases related to Holocarboxylase Synthetase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 multiple carboxylase deficiency 32.1 SLC5A6 PNPO PC HLCS BTD
2 biotin deficiency 31.7 SLC5A6 PC HLCS BTD
3 organic acidemia 30.6 LMBRD1 HLCS BTD
4 monocarboxylate transporter 1 deficiency 30.4 PC HLCS
5 biotinidase deficiency 30.2 SLC5A6 PNPO PC HLCS BTD
6 3-methylcrotonyl-coa carboxylase deficiency 30.0 LMBRD1 HLCS BTD
7 metabolic acidosis 10.7
8 lactic acidosis 10.5
9 autosomal recessive disease 10.5
10 abdominal obesity-metabolic syndrome 1 10.4
11 carbonic anhydrase va deficiency, hyperammonemia due to 10.4
12 exanthem 10.4
13 dermatitis 10.3
14 alopecia 10.2
15 hypoglycemia 10.2
16 hypertonia 10.2
17 glycogen storage disease iii 10.1
18 maple syrup urine disease 10.1
19 ocular motor apraxia 10.1
20 diabetes mellitus, ketosis-prone 10.1
21 alacrima, achalasia, and mental retardation syndrome 10.1
22 cardiac arrest 10.1
23 ichthyosis 10.1
24 cerebral palsy 10.1
25 glycogen storage disease 10.1
26 hyperglycemia 10.1
27 pustulosis of palm and sole 10.1
28 inherited metabolic disorder 10.1
29 psoriasis 10.1
30 hypotonia 10.1
31 thiamine metabolism dysfunction syndrome 2 10.1 SLC5A6 BTD
32 cerebral creatine deficiency syndrome 10.1 SLC6A8 PNPO
33 carnitine deficiency, systemic primary 10.0 PC BTD
34 vitamin metabolic disorder 10.0 PNPO LMBRD1
35 propionic acidemia 10.0 PC LMBRD1 HLCS
36 methylmalonic acidemia 9.9 PC LMBRD1 HLCS
37 hyperprolinemia, type ii 9.9 PNPO PLPBP
38 cerebral creatine deficiency syndrome 2 9.9 SLC6A8 PNPO BTD
39 aromatic l-amino acid decarboxylase deficiency 9.9 PNPO PLPBP
40 pyridoxamine 5-prime-phosphate oxidase deficiency 9.8 PNPO PLPBP BTD
41 amino acid metabolic disorder 9.8 SLC6A8 LMBRD1 BTD
42 glycine encephalopathy 9.8 PNPO PLPBP BTD
43 west syndrome 9.7 PNPO PLPBP BTD
44 early infantile epileptic encephalopathy 9.4 SLC6A8 PNPO PLPBP

Graphical network of the top 20 diseases related to Holocarboxylase Synthetase Deficiency:



Diseases related to Holocarboxylase Synthetase Deficiency

Symptoms & Phenotypes for Holocarboxylase Synthetase Deficiency

Human phenotypes related to Holocarboxylase Synthetase Deficiency:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
2 growth delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001510
3 irritability 58 31 hallmark (90%) Very frequent (99-80%) HP:0000737
4 anorexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002039
5 weight loss 58 31 hallmark (90%) Very frequent (99-80%) HP:0001824
6 keratoconjunctivitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001096
7 perioral eczema 58 31 hallmark (90%) Very frequent (99-80%) HP:0011127
8 seizure 31 hallmark (90%) HP:0001250
9 hypotonia 31 hallmark (90%) HP:0001252
10 hyperammonemia 58 31 frequent (33%) Frequent (79-30%) HP:0001987
11 tachypnea 58 31 frequent (33%) Frequent (79-30%) HP:0002789
12 organic aciduria 58 31 frequent (33%) Frequent (79-30%) HP:0001992
13 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
14 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
15 alopecia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001596
16 thrombocytopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001873
17 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
18 coma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001259
19 desquamation of skin soon after birth 58 31 occasional (7.5%) Occasional (29-5%) HP:0007549
20 seizures 58 Very frequent (99-80%)
21 muscular hypotonia 58 Very frequent (99-80%)
22 global developmental delay 31 HP:0001263
23 hypertonia 31 HP:0001276
24 feeding difficulties in infancy 31 HP:0008872
25 vomiting 31 HP:0002013
26 skin rash 31 HP:0000988
27 eczema 58 Occasional (29-5%)
28 metabolic acidosis 31 HP:0001942
29 generalized hypotonia 31 HP:0001290
30 hyperventilation 31 HP:0002883

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
hypertonia
irritability
lethargy
coma
more
Skin Nails Hair Hair:
alopecia

Skin Nails Hair Skin:
skin rash

Respiratory:
tachypnea
hyperventilation

Abdomen Gastrointestinal:
vomiting
feeding problems

Hematology:
thrombocytopenia

Metabolic Features:
metabolic acidosis
organic aciduria

Laboratory Abnormalities:
organic aciduria (elevated beta-hydroxyisovalerate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate, lactate, tiglylglycine)
mild-moderate hyperammonemia
holocarboxylase synthetase deficiency
normal serum biotin concentration

Clinical features from OMIM®:

253270 (Updated 05-Mar-2021)

UMLS symptoms related to Holocarboxylase Synthetase Deficiency:


seizures, vomiting, lethargy, exanthema

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

Search Clinical Trials , NIH Clinical Center for Holocarboxylase Synthetase Deficiency

Cochrane evidence based reviews: holocarboxylase synthetase deficiency

Genetic Tests for Holocarboxylase Synthetase Deficiency

Genetic tests related to Holocarboxylase Synthetase Deficiency:

# Genetic test Affiliating Genes
1 Holocarboxylase Synthetase Deficiency 29 HLCS
2 Biotin-Responsive Multiple Carboxylase Deficiencies 29

Anatomical Context for Holocarboxylase Synthetase Deficiency

MalaCards organs/tissues related to Holocarboxylase Synthetase Deficiency:

40
Liver, Skin

Publications for Holocarboxylase Synthetase Deficiency

Articles related to Holocarboxylase Synthetase Deficiency:

(show top 50) (show all 97)
# Title Authors PMID Year
1
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. 61 54 6 57
11735028 2001
2
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. 54 61 57 6
10190325 1999
3
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. 6 54 57 61
8319716 1993
4
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. 6 57
8817339 1996
5
Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. 6 57
7842009 1994
6
Clinical and biochemical findings on a child with multiple biotin-responsive carboxylase deficiencies. 57 6
6133032 1982
7
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. 61 54 6
11185745 2000
8
Mutations in the holocarboxylase synthetase gene HLCS. 57 61
16134170 2005
9
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. 61 6
12124727 2002
10
Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. 6
9396568 1997
11
Five patients with a biotin-responsive defect in holocarboxylase formation: evaluation of responsiveness to biotin therapy in vivo and comparative biochemical studies in vitro. 57
9128289 1997
12
Inheritable biotin-treatable disorders and associated phenomena. 57
3089241 1986
13
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. 57
3920902 1985
14
Enzyme studies in biotin-responsive disorders. 57
2864473 1985
15
Acetyl CoA carboxylase in cultured fibroblasts: differential biotin dependence in the two types of biotin-responsive multiple carboxylase deficiency. 57
6141728 1984
16
Deficient biotinidase activity in late-onset multiple carboxylase deficiency. 57
6848914 1983
17
The biotin-dependent carboxylase deficiencies. 57
6127031 1982
18
Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. 57
7102675 1982
19
Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. 57
6798072 1981
20
Clinical and metabolic abnormalities in a boy with dietary deficiency of biotin. 57
7322688 1981
21
Biotin-responsive multiple carboxylase deficiency of infantile onset. 57
7264799 1981
22
The neonatal form of biotin-responsive multiple carboxylase deficiency. 57
7264798 1981
23
Biochemical characterization of biotin-responsive multiple carboxylase deficiency: heterogeneity within the bio genetic complementation group. 57
6794361 1981
24
Defective biotin absorption in multiple carboxylase deficiency. 57
6114319 1981
25
Biotin-responsive carboxylase deficiency associated with subnormal plasma and urinary biotin. 57
6782477 1981
26
Biotin deficiency: an unusual complication of parenteral alimentation. 57
6782478 1981
27
Two forms of biotin-responsive multiple carboxylase deficiency. 57
6790844 1981
28
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. 54 61
19201116 2009
29
Management of a patient with holocarboxylase synthetase deficiency. 61 54
18974016 2008
30
Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency. 61 54
18442489 2008
31
Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands. 54 61
17417720 2007
32
Characterisation of the 1H and 13C NMR spectra of methylcitric acid. 54 61
16997619 2007
33
[Gene mutation analysis in four Chinese patients with multiple carboxylase deficiency]. 61 54
17274881 2006
34
Holocarboxylase synthetase deficiency: report of one case. 61 54
17407983 2006
35
Holocarboxylase synthetase deficiency presenting as ichthyosis. 54 61
16650223 2006
36
[Three congenital metabolic diseases in the Faeroe Islands. Incidence, clinical and molecular genetic characteristics of Faeroese children with glycogen storage disease type IIIA, carnitine transporter deficiency and holocarboxylase synthetase deficiency]. 61 54
16494802 2006
37
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. 61 54
16231399 2005
38
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. 61 54
16027709 2005
39
Molecular genetics of biotin metabolism: old vitamin, new science. 54 61
15992684 2005
40
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. 54 61
12855220 2003
41
[Holocarboxylase synthetase deficiency]. 61 54
11462701 2001
42
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. 61 54
11196112 2000
43
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. 61 54
10653324 2000
44
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. 54 61
10590022 1999
45
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. 54 61
10437643 1999
46
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. 54 61
10234606 1999
47
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. 61 54
10215065 1999
48
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. 54 61
9870216 1998
49
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. 54 61
9758715 1998
50
[Multiple carboxylase deficiency]. 61 54
9492625 1998

Variations for Holocarboxylase Synthetase Deficiency

ClinVar genetic disease variations for Holocarboxylase Synthetase Deficiency:

6 (show top 50) (show all 276)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HLCS NM_001352514.2(HLCS):c.2182G>A (p.Gly728Ser) SNV Pathogenic 1910 rs119103230 21:38132082-38132082 21:36759781-36759781
2 HLCS NM_001352514.2(HLCS):c.1096dup (p.Ile366fs) Duplication Pathogenic 1913 rs773102942 21:38309089-38309090 21:36936789-36936790
3 HLCS HLCS, 1-BP DEL, 780G Deletion Pathogenic 1906
4 HLCS NM_001352514.2(HLCS):c.2134C>T (p.Arg712Ter) SNV Pathogenic 426486 rs772791252 21:38132130-38132130 21:36759829-36759829
5 HLCS NM_001352514.2(HLCS):c.691G>T (p.Glu231Ter) SNV Pathogenic 578930 rs1569218416 21:38309495-38309495 21:36937195-36937195
6 HLCS NM_001352514.2(HLCS):c.1045G>T (p.Glu349Ter) SNV Pathogenic 582885 rs148324626 21:38309141-38309141 21:36936841-36936841
7 HLCS NM_001352514.2(HLCS):c.1496T>A (p.Leu499Ter) SNV Pathogenic 648263 rs1601779091 21:38302675-38302675 21:36930375-36930375
8 HLCS NM_001352514.2(HLCS):c.1025dup (p.Tyr342Ter) Duplication Pathogenic 654583 rs1601803431 21:38309160-38309161 21:36936860-36936861
9 HLCS NC_000021.9:g.(?_36938822)_(36939004_?)del Deletion Pathogenic 831691 21:38311122-38311304
10 HLCS NC_000021.9:g.(?_36765002)_(36767295_?)del Deletion Pathogenic 831787 21:38137303-38139596
11 HLCS NM_001352514.2(HLCS):c.1552del (p.Gly519fs) Deletion Pathogenic 862161 21:38302619-38302619 21:36930319-36930319
12 HLCS NM_001352514.2(HLCS):c.1698_1701del (p.Leu567fs) Deletion Pathogenic 949648 21:38269351-38269354 21:36897051-36897054
13 HLCS NM_001352514.2(HLCS):c.535C>T (p.Gln179Ter) SNV Pathogenic 961119 21:38309651-38309651 21:36937351-36937351
14 HLCS NM_001352514.2(HLCS):c.1963C>T (p.Arg655Trp) SNV Pathogenic 1909 rs119103229 21:38137471-38137471 21:36765170-36765170
15 HLCS NM_001352514.2(HLCS):c.2089G>A (p.Val697Met) SNV Pathogenic 1911 rs119103231 21:38137345-38137345 21:36765044-36765044
16 HLCS NM_001352514.2(HLCS):c.1223del (p.Gly408fs) Deletion Pathogenic 203777 rs771944310 21:38308963-38308963 21:36936663-36936663
17 HLCS NM_001352514.2(HLCS):c.1529T>A (p.Val510Asp) SNV Pathogenic/Likely pathogenic 550218 rs769499327 21:38302642-38302642 21:36930342-36930342
18 HLCS NM_001352514.2(HLCS):c.1960+5G>A SNV Pathogenic/Likely pathogenic 1912 rs753887925 21:38139514-38139514 21:36767213-36767213
19 HLCS NM_001352514.2(HLCS):c.1693_1694CT[3] (p.Ser566_Leu567insTer) Microsatellite Pathogenic/Likely pathogenic 557697 rs1555930523 21:38269352-38269353 21:36897052-36897053
20 HLCS NM_001352514.2(HLCS):c.1576C>T (p.Gln526Ter) SNV Pathogenic/Likely pathogenic 495865 rs1393866282 21:38302595-38302595 21:36930295-36930295
21 HLCS NM_001352514.2(HLCS):c.1088T>G (p.Leu363Arg) SNV Pathogenic/Likely pathogenic 1914 rs28934602 21:38309098-38309098 21:36936798-36936798
22 HLCS NM_001352514.2(HLCS):c.1151T>C (p.Leu384Pro) SNV Likely pathogenic 1907 rs119103227 21:38309035-38309035 21:36936735-36936735
23 HLCS NM_001352514.2(HLCS):c.1163G>C (p.Gly388Ala) SNV Likely pathogenic 369667 rs1057516035 21:38309023-38309023 21:36936723-36936723
24 HLCS NM_001352514.2(HLCS):c.857T>A (p.Leu286Ter) SNV Likely pathogenic 370852 rs144572349 21:38309329-38309329 21:36937029-36937029
25 HLCS NM_001352514.2(HLCS):c.1985G>A (p.Ser662Asn) SNV Likely pathogenic 428585 rs773398782 21:38137449-38137449 21:36765148-36765148
26 HLCS NM_001352514.2(HLCS):c.2527C>T (p.Gln843Ter) SNV Likely pathogenic 553590 rs1466111134 21:38126642-38126642 21:36754341-36754341
27 HLCS NM_001352514.2(HLCS):c.1620+1G>A SNV Likely pathogenic 554535 rs1555951858 21:38302550-38302550 21:36930250-36930250
28 HLCS NM_001352514.2(HLCS):c.2434C>T (p.Arg812Ter) SNV Likely pathogenic 203770 rs146448211 21:38128859-38128859 21:36756558-36756558
29 HLCS NM_001352514.2(HLCS):c.2280dup (p.Asn761fs) Duplication Likely pathogenic 551078 rs1555882068 21:38129012-38129013 21:36756711-36756712
30 HLCS NM_001352514.2(HLCS):c.1418dup (p.Glu474fs) Duplication Likely pathogenic 552198 rs1555955827 21:38308767-38308768 21:36936467-36936468
31 HLCS NM_001352514.2(HLCS):c.2260dup (p.Ser754fs) Duplication Likely pathogenic 553733 rs766163167 21:38129032-38129033 21:36756731-36756732
32 HLCS NM_001352514.2(HLCS):c.1621-2A>G SNV Likely pathogenic 553797 rs750728042 21:38269433-38269433 21:36897133-36897133
33 HLCS NM_001352514.2(HLCS):c.2201C>G (p.Ser734Ter) SNV Likely pathogenic 983890 21:38132063-38132063 21:36759762-36759762
34 HLCS NM_001352514.2(HLCS):c.2044G>T (p.Gly682Ter) SNV Likely pathogenic 983891 21:38137390-38137390 21:36765089-36765089
35 HLCS NM_001352514.2(HLCS):c.1957A>T (p.Lys653Ter) SNV Likely pathogenic 983892 21:38139522-38139522 21:36767221-36767221
36 HLCS NM_001352514.2(HLCS):c.1781C>G (p.Ser594Ter) SNV Likely pathogenic 983893 21:38269271-38269271 21:36896971-36896971
37 HLCS NM_001352514.2(HLCS):c.1771G>T (p.Glu591Ter) SNV Likely pathogenic 983894 21:38269281-38269281 21:36896981-36896981
38 HLCS NM_001352514.2(HLCS):c.1719C>A (p.Tyr573Ter) SNV Likely pathogenic 984052 21:38269333-38269333 21:36897033-36897033
39 HLCS NM_001352514.2(HLCS):c.1642C>T (p.Gln548Ter) SNV Likely pathogenic 984053 21:38269410-38269410 21:36897110-36897110
40 HLCS NM_001352514.2(HLCS):c.1434C>A (p.Cys478Ter) SNV Likely pathogenic 984054 21:38308752-38308752 21:36936452-36936452
41 HLCS NM_001352514.2(HLCS):c.1250T>A (p.Leu417Ter) SNV Likely pathogenic 984055 21:38308936-38308936 21:36936636-36936636
42 HLCS NM_001352514.2(HLCS):c.1132C>T (p.Gln378Ter) SNV Likely pathogenic 984056 21:38309054-38309054 21:36936754-36936754
43 HLCS NM_001352514.2(HLCS):c.886G>T (p.Glu296Ter) SNV Likely pathogenic 984057 21:38309300-38309300 21:36937000-36937000
44 HLCS NM_001352514.2(HLCS):c.840C>A (p.Tyr280Ter) SNV Likely pathogenic 984058 21:38309346-38309346 21:36937046-36937046
45 HLCS NM_001352514.2(HLCS):c.542C>A (p.Ser181Ter) SNV Likely pathogenic 984059 21:38309644-38309644 21:36937344-36937344
46 HLCS NM_001352514.2(HLCS):c.712_713del (p.Arg238fs) Deletion Likely pathogenic 556496 rs1284747916 21:38309473-38309474 21:36937173-36937174
47 HLCS NM_001352514.2(HLCS):c.2585A>C (p.Asp862Ala) SNV Likely pathogenic 803630 rs752737867 21:38126584-38126584 21:36754283-36754283
48 HLCS NM_001352514.2(HLCS):c.1073C>T (p.Thr358Met) SNV Conflicting interpretations of pathogenicity 203762 rs142524025 21:38309113-38309113 21:36936813-36936813
49 HLCS NM_001352514.2(HLCS):c.951C>T (p.Ser317=) SNV Conflicting interpretations of pathogenicity 705632 rs185480832 21:38309235-38309235 21:36936935-36936935
50 HLCS NM_001352514.2(HLCS):c.609C>T (p.Asp203=) SNV Conflicting interpretations of pathogenicity 759739 rs370118884 21:38309577-38309577 21:36937277-36937277

UniProtKB/Swiss-Prot genetic disease variations for Holocarboxylase Synthetase Deficiency:

73 (show all 23)
# Symbol AA change Variation ID SNP ID
1 HLCS p.Leu237Pro VAR_005084 rs119103227
2 HLCS p.Val333Glu VAR_009196 rs119854895
3 HLCS p.Thr462Ile VAR_009197 rs125635695
4 HLCS p.Val550Met VAR_009198 rs119103231
5 HLCS p.Asp571Asn VAR_009199 rs119103228
6 HLCS p.Gly581Ser VAR_009200 rs119103230
7 HLCS p.Arg508Trp VAR_013009 rs119103229
8 HLCS p.Leu216Arg VAR_021218 rs28934602
9 HLCS p.Asn511Lys VAR_021219
10 HLCS p.Gly582Arg VAR_021220 rs376899782
11 HLCS p.Arg183Pro VAR_046507
12 HLCS p.Arg360Ser VAR_046508 rs123066612
13 HLCS p.Val363Asp VAR_046509 rs769499327
14 HLCS p.Tyr456Cys VAR_046510 rs781603756
15 HLCS p.Leu470Ser VAR_046511 rs126182116
16 HLCS p.Gly518Glu VAR_046512
17 HLCS p.Val547Gly VAR_046513
18 HLCS p.Asp615Tyr VAR_046514
19 HLCS p.Asp634Asn VAR_046515 rs149399432
20 HLCS p.Asp634Tyr VAR_046516
21 HLCS p.Asp715Gly VAR_046517
22 HLCS p.Gly241Trp VAR_073074
23 HLCS p.Gly505Arg VAR_073075 rs155588505

Expression for Holocarboxylase Synthetase Deficiency

Search GEO for disease gene expression data for Holocarboxylase Synthetase Deficiency.

Pathways for Holocarboxylase Synthetase Deficiency

Pathways related to Holocarboxylase Synthetase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Biotin metabolism hsa00780

GO Terms for Holocarboxylase Synthetase Deficiency

Biological processes related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 biotin metabolic process GO:0006768 8.92 SLC5A6 PC HLCS BTD

Molecular functions related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pyridoxal phosphate binding GO:0030170 8.96 PNPO PLPBP
2 biotin binding GO:0009374 8.62 PC HLCS

Sources for Holocarboxylase Synthetase 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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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