HLCS DEFICIENCY
MCID: HLC001
MIFTS: 47

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 73 20 43 58 72 36 29 13 54 6 44 15 39 70
Early-Onset Multiple Carboxylase Deficiency 20 58 72
Hlcs Deficiency 57 43 72
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 72
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 72
Mcd Neonatal Form 72
Early-Onset Mcd 72

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 20-May-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: 79242 Definition A 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. Epidemiology The 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 description Clinical 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. Etiology Holocarboxylase 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 methods Some 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 diagnosis Conditions 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 diagnosis Prenatal 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 counseling HCS 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 treatment The 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. Prognosis In 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.

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 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 20-May-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 : 72 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 : 73 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 43)
# 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 respiratory failure 10.1
24 ichthyosis 10.1
25 cerebral palsy 10.1
26 glycogen storage disease 10.1
27 hyperglycemia 10.1
28 pustulosis of palm and sole 10.1
29 inherited metabolic disorder 10.1
30 psoriasis 10.1
31 hypotonia 10.1
32 thiamine metabolism dysfunction syndrome 2 10.1 SLC5A6 BTD
33 cerebral creatine deficiency syndrome 10.0 SLC6A8 PNPO
34 propionic acidemia 9.9 PC LMBRD1 HLCS
35 vitamin metabolic disorder 9.9 PNPO LMBRD1
36 methylmalonic acidemia 9.9 PC LMBRD1 HLCS
37 glutaric acidemia i 9.9 PC LMBRD1
38 cerebral creatine deficiency syndrome 2 9.9 SLC6A8 PNPO BTD
39 hyperprolinemia, type ii 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 aromatic l-amino acid decarboxylase deficiency 9.7 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 20-May-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 20-May-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
Skin

Publications for Holocarboxylase Synthetase Deficiency

Articles related to Holocarboxylase Synthetase Deficiency:

(show top 50) (show all 108)
# Title Authors PMID Year
1
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. 61 6 57 54
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. 57 54 6 61
8319716 1993
4
Mutations in the holocarboxylase synthetase gene HLCS. 61 57 6
16134170 2005
5
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. 6 57
8817339 1996
6
Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. 6 57
7842009 1994
7
Clinical and biochemical findings on a child with multiple biotin-responsive carboxylase deficiencies. 6 57
6133032 1982
8
Management of a patient with holocarboxylase synthetase deficiency. 6 61 54
18974016 2008
9
Holocarboxylase synthetase deficiency: report of one case. 54 61 6
17407983 2006
10
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. 54 61 6
16231399 2005
11
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. 61 6 54
10653324 2000
12
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. 6 54 61
11185745 2000
13
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. 6 61 54
10590022 1999
14
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. 61 6 54
9870216 1998
15
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. 6 54 61
8541348 1995
16
Holocarboxylase synthetase deficiency pre and post newborn screening. 61 6
27114915 2016
17
Severe neonatal holocarboxylase synthetase deficiency in west african siblings. 6 61
25690727 2015
18
[Delayed onset holocarboxylase synthetase deficiency with normal pyruvate carboxylase activity]. 6 61
24099927 2014
19
Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation. 61 6
24085707 2014
20
The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient. 61 6
21874615 2012
21
A novel molecular mechanism to explain biotin-unresponsive holocarboxylase synthetase deficiency. 61 6
21894551 2012
22
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. 6 61
20095979 2010
23
[Gene mutation analyses in Chinese children with multiple carboxylase deficiency]. 61 6
19806568 2009
24
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. 61 6
18429047 2008
25
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. 61 6
12633764 2003
26
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. 61 6
12124727 2002
27
A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. 6
26938784 2016
28
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
29
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. 6
25087612 2014
30
Holocarboxylase synthetase acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7. 6
24239178 2014
31
Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. 6
24215330 2013
32
Effects of single-nucleotide polymorphisms in the human holocarboxylase synthetase gene on enzyme catalysis. 6
22027809 2012
33
The polypeptide Syn67 interacts physically with human holocarboxylase synthetase, but is not a target for biotinylation. 6
20026029 2010
34
[Diagnosis, treatment and gene mutation analysis in children with holocarboxylase synthetas deficiency]. 6
19695181 2009
35
N- and C-terminal domains in human holocarboxylase synthetase participate in substrate recognition. 6
19157941 2009
36
Expression in Escherichia coli of N- and C-terminally deleted human holocarboxylase synthetase. Influence of the N-terminus on biotinylation and identification of a minimum functional protein. 6
11124959 2001
37
Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency. 6
10068510 1999
38
Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. 6
9396568 1997
39
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
40
Inheritable biotin-treatable disorders and associated phenomena. 57
3089241 1986
41
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. 57
3920902 1985
42
Enzyme studies in biotin-responsive disorders. 57
2864473 1985
43
Acetyl CoA carboxylase in cultured fibroblasts: differential biotin dependence in the two types of biotin-responsive multiple carboxylase deficiency. 57
6141728 1984
44
Deficient biotinidase activity in late-onset multiple carboxylase deficiency. 57
6848914 1983
45
The biotin-dependent carboxylase deficiencies. 57
6127031 1982
46
Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. 57
7102675 1982
47
Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. 57
6798072 1981
48
Clinical and metabolic abnormalities in a boy with dietary deficiency of biotin. 57
7322688 1981
49
The neonatal form of biotin-responsive multiple carboxylase deficiency. 57
7264798 1981
50
Biotin-responsive multiple carboxylase deficiency of infantile onset. 57
7264799 1981

Variations for Holocarboxylase Synthetase Deficiency

ClinVar genetic disease variations for Holocarboxylase Synthetase Deficiency:

6 (show top 50) (show all 283)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HLCS NM_001352514.2(HLCS):c.2182G>A (p.Gly728Ser) SNV Pathogenic 1910 rs119103230 GRCh37: 21:38132082-38132082
GRCh38: 21:36759781-36759781
2 HLCS NM_001352514.2(HLCS):c.1096dup (p.Ile366fs) Duplication Pathogenic 1913 rs773102942 GRCh37: 21:38309089-38309090
GRCh38: 21:36936789-36936790
3 HLCS HLCS, 1-BP DEL, 780G Deletion Pathogenic 1906 GRCh37:
GRCh38:
4 HLCS NM_001352514.2(HLCS):c.2134C>T (p.Arg712Ter) SNV Pathogenic 426486 rs772791252 GRCh37: 21:38132130-38132130
GRCh38: 21:36759829-36759829
5 HLCS NM_001352514.2(HLCS):c.691G>T (p.Glu231Ter) SNV Pathogenic 578930 rs1569218416 GRCh37: 21:38309495-38309495
GRCh38: 21:36937195-36937195
6 HLCS NM_001352514.2(HLCS):c.1045G>T (p.Glu349Ter) SNV Pathogenic 582885 rs148324626 GRCh37: 21:38309141-38309141
GRCh38: 21:36936841-36936841
7 HLCS NM_001352514.2(HLCS):c.1496T>A (p.Leu499Ter) SNV Pathogenic 648263 rs1601779091 GRCh37: 21:38302675-38302675
GRCh38: 21:36930375-36930375
8 HLCS NM_001352514.2(HLCS):c.1025dup (p.Tyr342Ter) Duplication Pathogenic 654583 rs1601803431 GRCh37: 21:38309160-38309161
GRCh38: 21:36936860-36936861
9 HLCS NC_000021.9:g.(?_36938822)_(36939004_?)del Deletion Pathogenic 831691 GRCh37: 21:38311122-38311304
GRCh38:
10 HLCS NC_000021.9:g.(?_36765002)_(36767295_?)del Deletion Pathogenic 831787 GRCh37: 21:38137303-38139596
GRCh38:
11 HLCS NM_001352514.2(HLCS):c.1552del (p.Gly519fs) Deletion Pathogenic 862161 GRCh37: 21:38302619-38302619
GRCh38: 21:36930319-36930319
12 HLCS NM_001352514.2(HLCS):c.535C>T (p.Gln179Ter) SNV Pathogenic 961119 GRCh37: 21:38309651-38309651
GRCh38: 21:36937351-36937351
13 HLCS NM_001352514.2(HLCS):c.1960+1G>A SNV Pathogenic 1034193 GRCh37: 21:38139518-38139518
GRCh38: 21:36767217-36767217
14 HLCS NM_001352514.2(HLCS):c.1963C>T (p.Arg655Trp) SNV Pathogenic 1909 rs119103229 GRCh37: 21:38137471-38137471
GRCh38: 21:36765170-36765170
15 HLCS NM_001352514.2(HLCS):c.2089G>A (p.Val697Met) SNV Pathogenic 1911 rs119103231 GRCh37: 21:38137345-38137345
GRCh38: 21:36765044-36765044
16 HLCS NM_001352514.2(HLCS):c.1698_1701del (p.Leu567fs) Deletion Pathogenic 949648 GRCh37: 21:38269351-38269354
GRCh38: 21:36897051-36897054
17 HLCS NM_001352514.2(HLCS):c.1223del (p.Gly408fs) Deletion Pathogenic 203777 rs771944310 GRCh37: 21:38308963-38308963
GRCh38: 21:36936663-36936663
18 HLCS NM_001352514.2(HLCS):c.1960+5G>A SNV Pathogenic/Likely pathogenic 1912 rs753887925 GRCh37: 21:38139514-38139514
GRCh38: 21:36767213-36767213
19 HLCS NM_001352514.2(HLCS):c.1529T>A (p.Val510Asp) SNV Pathogenic/Likely pathogenic 550218 rs769499327 GRCh37: 21:38302642-38302642
GRCh38: 21:36930342-36930342
20 HLCS NM_001352514.2(HLCS):c.1693_1694CT[3] (p.Ser566_Leu567insTer) Microsatellite Pathogenic/Likely pathogenic 557697 rs1555930523 GRCh37: 21:38269352-38269353
GRCh38: 21:36897052-36897053
21 HLCS NM_001352514.2(HLCS):c.1576C>T (p.Gln526Ter) SNV Pathogenic/Likely pathogenic 495865 rs1393866282 GRCh37: 21:38302595-38302595
GRCh38: 21:36930295-36930295
22 HLCS NM_001352514.2(HLCS):c.1088T>G (p.Leu363Arg) SNV Pathogenic/Likely pathogenic 1914 rs28934602 GRCh37: 21:38309098-38309098
GRCh38: 21:36936798-36936798
23 HLCS NM_001352514.2(HLCS):c.1151T>C (p.Leu384Pro) SNV Likely pathogenic 1907 rs119103227 GRCh37: 21:38309035-38309035
GRCh38: 21:36936735-36936735
24 HLCS NM_001352514.2(HLCS):c.1163G>C (p.Gly388Ala) SNV Likely pathogenic 369667 rs1057516035 GRCh37: 21:38309023-38309023
GRCh38: 21:36936723-36936723
25 HLCS NM_001352514.2(HLCS):c.857T>A (p.Leu286Ter) SNV Likely pathogenic 370852 rs144572349 GRCh37: 21:38309329-38309329
GRCh38: 21:36937029-36937029
26 HLCS NM_001352514.2(HLCS):c.1985G>A (p.Ser662Asn) SNV Likely pathogenic 428585 rs773398782 GRCh37: 21:38137449-38137449
GRCh38: 21:36765148-36765148
27 HLCS NM_001352514.2(HLCS):c.2260dup (p.Ser754fs) Duplication Likely pathogenic 553733 rs766163167 GRCh37: 21:38129032-38129033
GRCh38: 21:36756731-36756732
28 HLCS NM_001352514.2(HLCS):c.1621-2A>G SNV Likely pathogenic 553797 rs750728042 GRCh37: 21:38269433-38269433
GRCh38: 21:36897133-36897133
29 HLCS NM_001352514.2(HLCS):c.2434C>T (p.Arg812Ter) SNV Likely pathogenic 203770 rs146448211 GRCh37: 21:38128859-38128859
GRCh38: 21:36756558-36756558
30 HLCS NM_001352514.2(HLCS):c.2280dup (p.Asn761fs) Duplication Likely pathogenic 551078 rs1555882068 GRCh37: 21:38129012-38129013
GRCh38: 21:36756711-36756712
31 HLCS NM_001352514.2(HLCS):c.2527C>T (p.Gln843Ter) SNV Likely pathogenic 553590 rs1466111134 GRCh37: 21:38126642-38126642
GRCh38: 21:36754341-36754341
32 HLCS NM_001352514.2(HLCS):c.1418dup (p.Glu474fs) Duplication Likely pathogenic 552198 rs1555955827 GRCh37: 21:38308767-38308768
GRCh38: 21:36936467-36936468
33 HLCS NM_001352514.2(HLCS):c.1620+1G>A SNV Likely pathogenic 554535 rs1555951858 GRCh37: 21:38302550-38302550
GRCh38: 21:36930250-36930250
34 HLCS NM_001352514.2(HLCS):c.2201C>G (p.Ser734Ter) SNV Likely pathogenic 983890 GRCh37: 21:38132063-38132063
GRCh38: 21:36759762-36759762
35 HLCS NM_001352514.2(HLCS):c.2044G>T (p.Gly682Ter) SNV Likely pathogenic 983891 GRCh37: 21:38137390-38137390
GRCh38: 21:36765089-36765089
36 HLCS NM_001352514.2(HLCS):c.1957A>T (p.Lys653Ter) SNV Likely pathogenic 983892 GRCh37: 21:38139522-38139522
GRCh38: 21:36767221-36767221
37 HLCS NM_001352514.2(HLCS):c.1781C>G (p.Ser594Ter) SNV Likely pathogenic 983893 GRCh37: 21:38269271-38269271
GRCh38: 21:36896971-36896971
38 HLCS NM_001352514.2(HLCS):c.1771G>T (p.Glu591Ter) SNV Likely pathogenic 983894 GRCh37: 21:38269281-38269281
GRCh38: 21:36896981-36896981
39 HLCS NM_001352514.2(HLCS):c.1719C>A (p.Tyr573Ter) SNV Likely pathogenic 984052 GRCh37: 21:38269333-38269333
GRCh38: 21:36897033-36897033
40 HLCS NM_001352514.2(HLCS):c.1642C>T (p.Gln548Ter) SNV Likely pathogenic 984053 GRCh37: 21:38269410-38269410
GRCh38: 21:36897110-36897110
41 HLCS NM_001352514.2(HLCS):c.1434C>A (p.Cys478Ter) SNV Likely pathogenic 984054 GRCh37: 21:38308752-38308752
GRCh38: 21:36936452-36936452
42 HLCS NM_001352514.2(HLCS):c.1250T>A (p.Leu417Ter) SNV Likely pathogenic 984055 GRCh37: 21:38308936-38308936
GRCh38: 21:36936636-36936636
43 HLCS NM_001352514.2(HLCS):c.1132C>T (p.Gln378Ter) SNV Likely pathogenic 984056 GRCh37: 21:38309054-38309054
GRCh38: 21:36936754-36936754
44 HLCS NM_001352514.2(HLCS):c.886G>T (p.Glu296Ter) SNV Likely pathogenic 984057 GRCh37: 21:38309300-38309300
GRCh38: 21:36937000-36937000
45 HLCS NM_001352514.2(HLCS):c.840C>A (p.Tyr280Ter) SNV Likely pathogenic 984058 GRCh37: 21:38309346-38309346
GRCh38: 21:36937046-36937046
46 HLCS NM_001352514.2(HLCS):c.542C>A (p.Ser181Ter) SNV Likely pathogenic 984059 GRCh37: 21:38309644-38309644
GRCh38: 21:36937344-36937344
47 HLCS NM_001352514.2(HLCS):c.712_713del (p.Arg238fs) Deletion Likely pathogenic 556496 rs1284747916 GRCh37: 21:38309473-38309474
GRCh38: 21:36937173-36937174
48 HLCS NM_001352514.2(HLCS):c.2585A>C (p.Asp862Ala) SNV Likely pathogenic 803630 rs752737867 GRCh37: 21:38126584-38126584
GRCh38: 21:36754283-36754283
49 HLCS NM_001352514.2(HLCS):c.1073C>T (p.Thr358Met) SNV Conflicting interpretations of pathogenicity 203762 rs142524025 GRCh37: 21:38309113-38309113
GRCh38: 21:36936813-36936813
50 HLCS NM_001352514.2(HLCS):c.1857C>A (p.Ala619=) SNV Conflicting interpretations of pathogenicity 339962 rs759178651 GRCh37: 21:38269195-38269195
GRCh38: 21:36896895-36896895

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

72 (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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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