HLCS DEFICIENCY
MCID: HLC001
MIFTS: 53

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 76 53 25 59 75 37 29 13 55 6 44 15 40 73
Early-Onset Multiple Carboxylase Deficiency 53 59 75
Hlcs Deficiency 57 25 75
Multiple Carboxylase Deficiency, Neonatal Form 57 25
Neonatal Multiple Carboxylase Deficiency 53 59
Early-Onset Biotin-Responsive Multiple Carboxylase Deficiency 25
Biotin-Responsive Multiple Carboxylase Deficiencies 29
Biotin-Responsive Multiple Carboxylase Deficiency 75
Multiple Carboxylase Deficiency - Neonatal Onset 12
Multiple Carboxylase Deficiency, Early Onset 57
Early-Onset Combined Carboxylase Deficiency 25
Infantile Multiple Carboxylase Deficiency 25
Biotin- Ligase Deficiency 12
Holocarboxylase Synthetase 13
Biotin-Responsive Mcd 75
Mcd Neonatal Form 75
Early-Onset Mcd 75

Characteristics:

Orphanet epidemiological data:

59
holocarboxylase synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
age of onset - birth to 15 months


HPO:

32
holocarboxylase synthetase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Holocarboxylase Synthetase Deficiency

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79242Disease definitionHolocarboxylase synthetase (HCS) deficiency is a life-threatening early-onset form of multiple carboxylase deficiency (see this term), 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 recessivetrait. 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 biotinidase 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. The drugs Biotin and Folic Acid have been mentioned in the context of this disorder. Affiliated tissues include testes and skin, and related phenotypes are seizures and ataxia

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

Genetics Home Reference : 25 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, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.

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)

UniProtKB/Swiss-Prot : 75 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 : 76 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 30)
# Related Disease Score Top Affiliating Genes
1 multiple carboxylase deficiency 33.5 BTD HLCS PC
2 biotinidase deficiency 32.9 BTD HLCS
3 biotin deficiency 32.2 BTD HLCS PC
4 organic acidemia 30.3 BTD HLCS HMGCL
5 diabetes mellitus, ketosis-prone 10.2
6 alopecia 10.2
7 monocarboxylate transporter 1 deficiency 10.1 HLCS PC
8 cerebral palsy 10.1
9 glycogen storage disease 10.1
10 ichthyosis 10.1
11 dermatitis 10.1
12 lactic acidosis 10.1
13 psoriasis 10.1
14 acyl-coa dehydrogenase, medium-chain, deficiency of 10.1 ACADL BTD
15 3-methylcrotonyl-coa carboxylase deficiency 10.1 HMGCL LMBRD1
16 down syndrome 10.1
17 reye syndrome 10.1 HMGCL PC
18 acyl-coa dehydrogenase, short-chain, deficiency of 10.1 ACADL SLC25A13
19 carnitine palmitoyltransferase ii deficiency, infantile 10.0 ACADL SLC25A20
20 carbonic anhydrase va deficiency, hyperammonemia due to 10.0 SLC25A13 SLC25A20
21 vitamin metabolic disorder 10.0 LMBRD1 MTHFR
22 propionic acidemia 10.0 HLCS HMGCL SLC25A13
23 encephalomalacia 10.0 MTHFR PC
24 hypoglycemia 10.0 ACADL HADH SLC25A20
25 hyperphenylalaninemia, bh4-deficient, a 9.9 SLC25A13 SLC25A20
26 carnitine palmitoyltransferase i deficiency 9.9 HADH SLC25A20
27 acyl-coa dehydrogenase, very long-chain, deficiency of 9.7 ACADL HADH HMGCL SLC25A13 SLC25A20
28 amino acid metabolic disorder 9.6 BTD MMD MMUT MTHFR
29 transcobalamin ii deficiency 9.5 LMBRD1 MMD MMUT MTHFR
30 methylmalonic aciduria due to methylmalonyl-coa mutase deficiency 9.4 HLCS HMGCL LMBRD1 MMUT MTHFR PC

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



Diseases related to Holocarboxylase Synthetase Deficiency

Symptoms & Phenotypes for Holocarboxylase Synthetase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
hypertonia
irritability
coma
lethargy
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

Human phenotypes related to Holocarboxylase Synthetase Deficiency:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
3 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
4 nausea and vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002017
5 irritability 59 32 hallmark (90%) Very frequent (99-80%) HP:0000737
6 weight loss 59 32 hallmark (90%) Very frequent (99-80%) HP:0001824
7 respiratory distress 59 32 frequent (33%) Frequent (79-30%) HP:0002098
8 growth delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001510
9 alopecia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001596
10 thrombocytopenia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001873
11 anorexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002039
12 coma 59 32 occasional (7.5%) Occasional (29-5%) HP:0001259
13 hyperammonemia 59 32 frequent (33%) Frequent (79-30%) HP:0001987
14 lethargy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001254
15 tachypnea 59 32 frequent (33%) Frequent (79-30%) HP:0002789
16 keratoconjunctivitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001096
17 organic aciduria 59 32 frequent (33%) Frequent (79-30%) HP:0001992
18 desquamation of skin soon after birth 59 32 occasional (7.5%) Occasional (29-5%) HP:0007549
19 perioral eczema 59 32 hallmark (90%) Very frequent (99-80%) HP:0011127
20 global developmental delay 32 HP:0001263
21 hypertonia 32 HP:0001276
22 feeding difficulties in infancy 32 HP:0008872
23 vomiting 32 HP:0002013
24 skin rash 32 HP:0000988
25 eczema 59 Occasional (29-5%)
26 metabolic acidosis 32 HP:0001942
27 generalized hypotonia 32 HP:0001290
28 hyperventilation 32 HP:0002883

UMLS symptoms related to Holocarboxylase Synthetase Deficiency:


seizures, vomiting, lethargy, exanthema

MGI Mouse Phenotypes related to Holocarboxylase Synthetase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.76 ACADL BTD HADH HMGCL MMUT MTHFR
2 liver/biliary system MP:0005370 9.43 ACADL HMGCL MMUT MTHFR SLC25A13 SLC25A20
3 renal/urinary system MP:0005367 9.1 ACADL BTD HADH MMUT SLC25A13 SLC25A20

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

Drugs for Holocarboxylase Synthetase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Biotin Approved, Investigational, Nutraceutical Not Applicable 58-85-5 171548
2
Folic Acid Approved, Nutraceutical, Vet_approved Not Applicable 59-30-3 6037
3 Vitamin B9 Not Applicable
4 Vitamins Not Applicable
5 Micronutrients Not Applicable
6 Trace Elements Not Applicable
7 Folate Not Applicable
8 Vitamin B7 Not Applicable
9 Vitamin B Complex Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of ORL-1B in Patients With Biotinidase Deficiency Completed NCT03269045 Phase 1, Phase 2 ORL-1B
2 Biotin Status in Pregnancy Completed NCT00894920 Not Applicable
3 BIOtinidase Test In Optic-Neuropathy Completed NCT03268681
4 Biotin Deficiency and Restless Legs Syndrome Completed NCT02011191 Not Applicable

Search 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:

41
Testes, Skin

Publications for Holocarboxylase Synthetase Deficiency

Articles related to Holocarboxylase Synthetase Deficiency:

(show all 48)
# Title Authors Year
1
Psoriasis-like Dermatitis in Adulthood: a Skin Manifestation of Holocarboxylase Synthetase Deficiency. ( 29701239 )
2018
2
Paracentric Inversion of Chromosome 21 Leading to Disruption of the HLCS Gene in a Family with Holocarboxylase Synthetase Deficiency. ( 27518780 )
2016
3
Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review. ( 26754537 )
2016
4
Holocarboxylase synthetase deficiency pre and post newborn screening. ( 27114915 )
2016
5
Severe neonatal holocarboxylase synthetase deficiency in west african siblings. ( 25690727 )
2015
6
Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation. ( 24085707 )
2013
7
The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient. ( 21874615 )
2012
8
A novel molecular mechanism to explain biotin-unresponsive holocarboxylase synthetase deficiency. ( 21894551 )
2012
9
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. ( 20095979 )
2010
10
Positive newborn screen in the biochemically normal infant of a mother with treated holocarboxylase synthetase deficiency. ( 19357990 )
2009
11
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. ( 19201116 )
2009
12
Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency. ( 18442489 )
2008
13
Management of a patient with holocarboxylase synthetase deficiency. ( 18974016 )
2008
14
[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]. ( 16494802 )
2006
15
Holocarboxylase synthetase deficiency presenting as ichthyosis. ( 16650223 )
2006
16
Holocarboxylase synthetase deficiency: report of one case. ( 17407983 )
2006
17
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. ( 16027709 )
2005
18
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. ( 16231399 )
2005
19
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. ( 12855220 )
2003
20
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. ( 12633764 )
2003
21
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. ( 12124727 )
2002
22
[Holocarboxylase synthetase deficiency]. ( 11462701 )
2001
23
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. ( 11735028 )
2001
24
Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation. ( 10770035 )
2000
25
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. ( 11185745 )
2000
26
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. ( 11196112 )
2000
27
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. ( 10653324 )
2000
28
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. ( 10437643 )
1999
29
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. ( 10234606 )
1999
30
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. ( 10190325 )
1999
31
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. ( 10590022 )
1999
32
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. ( 10215065 )
1999
33
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. ( 9686819 )
1998
34
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. ( 9645047 )
1998
35
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. ( 9758715 )
1998
36
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. ( 9870216 )
1998
37
Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency. ( 9183268 )
1997
38
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate. ( 8814349 )
1996
39
Late-onset holocarboxylase synthetase deficiency. ( 8982946 )
1996
40
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. ( 8541348 )
1995
41
Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy. ( 8006369 )
1994
42
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. ( 8319716 )
1993
43
Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. ( 2515372 )
1989
44
A new case of holocarboxylase synthetase deficiency. ( 2515377 )
1989
45
Biotin holocarboxylase synthetase deficiency. ( 3860175 )
1985
46
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. ( 6811711 )
1982
47
Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. ( 7226522 )
1981
48
Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia. ( 7365583 )
1980

Variations for Holocarboxylase Synthetase Deficiency

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

75 (show all 23)
# Symbol AA change Variation ID SNP ID
1 HLCS p.Leu237Pro VAR_005084 rs119103227
2 HLCS p.Val333Glu VAR_009196
3 HLCS p.Thr462Ile VAR_009197
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
13 HLCS p.Val363Asp VAR_046509 rs769499327
14 HLCS p.Tyr456Cys VAR_046510 rs781603756
15 HLCS p.Leu470Ser VAR_046511
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

ClinVar genetic disease variations for Holocarboxylase Synthetase Deficiency:

6 (show top 50) (show all 297)
# Gene Variation Type Significance SNP ID Assembly Location
1 HLCS HLCS, 1-BP DEL, 780G deletion Pathogenic
2 HLCS NM_000411.6(HLCS): c.710T> C (p.Leu237Pro) single nucleotide variant Likely pathogenic rs119103227 GRCh37 Chromosome 21, 38309035: 38309035
3 HLCS NM_000411.6(HLCS): c.710T> C (p.Leu237Pro) single nucleotide variant Likely pathogenic rs119103227 GRCh38 Chromosome 21, 36936735: 36936735
4 HLCS NM_001242785.2(HLCS): c.1711G> A (p.Asp571Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs119103228 GRCh37 Chromosome 21, 38132112: 38132112
5 HLCS NM_001242785.2(HLCS): c.1711G> A (p.Asp571Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs119103228 GRCh38 Chromosome 21, 36759811: 36759811
6 HLCS NM_000411.6(HLCS): c.1522C> T (p.Arg508Trp) single nucleotide variant Pathogenic rs119103229 GRCh37 Chromosome 21, 38137471: 38137471
7 HLCS NM_000411.6(HLCS): c.1522C> T (p.Arg508Trp) single nucleotide variant Pathogenic rs119103229 GRCh38 Chromosome 21, 36765170: 36765170
8 HLCS NM_000411.6(HLCS): c.1741G> A (p.Gly581Ser) single nucleotide variant Pathogenic rs119103230 GRCh37 Chromosome 21, 38132082: 38132082
9 HLCS NM_000411.6(HLCS): c.1741G> A (p.Gly581Ser) single nucleotide variant Pathogenic rs119103230 GRCh38 Chromosome 21, 36759781: 36759781
10 HLCS NM_000411.6(HLCS): c.1648G> A (p.Val550Met) single nucleotide variant Pathogenic/Likely pathogenic rs119103231 GRCh37 Chromosome 21, 38137345: 38137345
11 HLCS NM_000411.6(HLCS): c.1648G> A (p.Val550Met) single nucleotide variant Pathogenic/Likely pathogenic rs119103231 GRCh38 Chromosome 21, 36765044: 36765044
12 HLCS NM_000411.7(HLCS): c.1519+5G> A single nucleotide variant Likely pathogenic rs753887925 GRCh38 Chromosome 21, 36767213: 36767213
13 HLCS NM_000411.7(HLCS): c.1519+5G> A single nucleotide variant Likely pathogenic rs753887925 GRCh37 Chromosome 21, 38139514: 38139514
14 HLCS NM_000411.7(HLCS): c.655dup (p.Ile219Asnfs) duplication Pathogenic rs773102942 GRCh37 Chromosome 21, 38309090: 38309090
15 HLCS NM_000411.7(HLCS): c.655dup (p.Ile219Asnfs) duplication Pathogenic rs773102942 GRCh38 Chromosome 21, 36936790: 36936790
16 HLCS NM_000411.6(HLCS): c.647T> G (p.Leu216Arg) single nucleotide variant Likely pathogenic rs28934602 GRCh37 Chromosome 21, 38309098: 38309098
17 HLCS NM_000411.6(HLCS): c.647T> G (p.Leu216Arg) single nucleotide variant Likely pathogenic rs28934602 GRCh38 Chromosome 21, 36936798: 36936798
18 HLCS NM_000411.6(HLCS): c.1179+7delT deletion Benign/Likely benign rs140568778 GRCh37 Chromosome 21, 38302544: 38302544
19 HLCS NM_000411.6(HLCS): c.1179+7delT deletion Benign/Likely benign rs140568778 GRCh38 Chromosome 21, 36930244: 36930244
20 HLCS NM_000411.6(HLCS): c.834C> T (p.Ser278=) single nucleotide variant Benign/Likely benign rs1065758 GRCh37 Chromosome 21, 38308911: 38308911
21 HLCS NM_000411.6(HLCS): c.834C> T (p.Ser278=) single nucleotide variant Benign/Likely benign rs1065758 GRCh38 Chromosome 21, 36936611: 36936611
22 HLCS NM_000411.7(HLCS): c.1710C> T (p.Asn570=) single nucleotide variant Benign rs148709879 GRCh37 Chromosome 21, 38132113: 38132113
23 HLCS NM_000411.7(HLCS): c.1710C> T (p.Asn570=) single nucleotide variant Benign rs148709879 GRCh38 Chromosome 21, 36759812: 36759812
24 HLCS NM_000411.7(HLCS): c.1920C> T (p.Val640=) single nucleotide variant Benign/Likely benign rs61732507 GRCh37 Chromosome 21, 38128932: 38128932
25 HLCS NM_000411.7(HLCS): c.1920C> T (p.Val640=) single nucleotide variant Benign/Likely benign rs61732507 GRCh38 Chromosome 21, 36756631: 36756631
26 HLCS NM_000411.6(HLCS): c.2174G> A (p.Arg725Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs147474255 GRCh37 Chromosome 21, 38126554: 38126554
27 HLCS NM_000411.6(HLCS): c.2174G> A (p.Arg725Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs147474255 GRCh38 Chromosome 21, 36754253: 36754253
28 HLCS NM_000411.6(HLCS): c.126G> T (p.Glu42Asp) single nucleotide variant Benign/Likely benign rs61732504 GRCh37 Chromosome 21, 38309619: 38309619
29 HLCS NM_000411.6(HLCS): c.126G> T (p.Glu42Asp) single nucleotide variant Benign/Likely benign rs61732504 GRCh38 Chromosome 21, 36937319: 36937319
30 HLCS NM_000411.7(HLCS): c.285C> T (p.Pro95=) single nucleotide variant Benign rs2230182 GRCh37 Chromosome 21, 38309460: 38309460
31 HLCS NM_000411.7(HLCS): c.285C> T (p.Pro95=) single nucleotide variant Benign rs2230182 GRCh38 Chromosome 21, 36937160: 36937160
32 HLCS NM_000411.6(HLCS): c.286G> A (p.Val96Ile) single nucleotide variant Benign/Likely benign rs61732502 GRCh37 Chromosome 21, 38309459: 38309459
33 HLCS NM_000411.6(HLCS): c.286G> A (p.Val96Ile) single nucleotide variant Benign/Likely benign rs61732502 GRCh38 Chromosome 21, 36937159: 36937159
34 HLCS NM_000411.6(HLCS): c.971G> A (p.Arg324His) single nucleotide variant Benign rs61732501 GRCh37 Chromosome 21, 38308774: 38308774
35 HLCS NM_000411.6(HLCS): c.971G> A (p.Arg324His) single nucleotide variant Benign rs61732501 GRCh38 Chromosome 21, 36936474: 36936474
36 HLCS NM_000411.7(HLCS): c.-405T> C single nucleotide variant Benign rs117476389 GRCh37 Chromosome 21, 38362470: 38362470
37 HLCS NM_000411.7(HLCS): c.-405T> C single nucleotide variant Benign rs117476389 GRCh38 Chromosome 21, 36990170: 36990170
38 HLCS NM_000411.7(HLCS): c.-393+11G> T single nucleotide variant Benign/Likely benign rs557368288 GRCh37 Chromosome 21, 38362447: 38362447
39 HLCS NM_000411.7(HLCS): c.-393+11G> T single nucleotide variant Benign/Likely benign rs557368288 GRCh38 Chromosome 21, 36990147: 36990147
40 HLCS NM_000411.7(HLCS): c.1624C> T (p.Gln542Ter) single nucleotide variant Pathogenic rs794727957 GRCh37 Chromosome 21, 38137369: 38137369
41 HLCS NM_000411.7(HLCS): c.1624C> T (p.Gln542Ter) single nucleotide variant Pathogenic rs794727957 GRCh38 Chromosome 21, 36765068: 36765068
42 HLCS NM_000411.6(HLCS): c.2059G> A (p.Val687Ile) single nucleotide variant Uncertain significance rs145648338 GRCh38 Chromosome 21, 36754368: 36754368
43 HLCS NM_000411.6(HLCS): c.2059G> A (p.Val687Ile) single nucleotide variant Uncertain significance rs145648338 GRCh37 Chromosome 21, 38126669: 38126669
44 HLCS NM_000411.6(HLCS): c.1993C> T (p.Arg665Ter) single nucleotide variant Likely pathogenic rs146448211 GRCh38 Chromosome 21, 36756558: 36756558
45 HLCS NM_000411.6(HLCS): c.1993C> T (p.Arg665Ter) single nucleotide variant Likely pathogenic rs146448211 GRCh37 Chromosome 21, 38128859: 38128859
46 HLCS NM_000411.7(HLCS): c.1921G> A (p.Val641Met) single nucleotide variant Benign/Likely benign rs150665851 GRCh38 Chromosome 21, 36756630: 36756630
47 HLCS NM_000411.7(HLCS): c.1921G> A (p.Val641Met) single nucleotide variant Benign/Likely benign rs150665851 GRCh37 Chromosome 21, 38128931: 38128931
48 HLCS NM_000411.6(HLCS): c.1672G> A (p.Glu558Lys) single nucleotide variant Benign/Likely benign rs149736764 GRCh37 Chromosome 21, 38137321: 38137321
49 HLCS NM_000411.6(HLCS): c.1672G> A (p.Glu558Lys) single nucleotide variant Benign/Likely benign rs149736764 GRCh38 Chromosome 21, 36765020: 36765020
50 HLCS NM_000411.6(HLCS): c.890G> A (p.Arg297Gln) single nucleotide variant Uncertain significance rs146030669 GRCh37 Chromosome 21, 38308855: 38308855

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:

37
# Name Kegg Source Accession
1 Biotin metabolism hsa00780

Pathways related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.33 ACADL BTD HADH HLCS HMGCL LMBRD1
2
Show member pathways
12.57 ACADL HADH HMGCL MMUT SLC25A20
3
Show member pathways
12.01 MMUT MTHFR PC
4
Show member pathways
11.71 BTD HLCS LMBRD1 MMUT MTHFR PC
5
Show member pathways
11.68 HADH HMGCL MMUT
6 11.42 HADH HMGCL MMUT PC
7
Show member pathways
11.36 ACADL HADH MMUT
8
Show member pathways
11.26 ACADL HADH
9
Show member pathways
11.22 ACADL HADH SLC25A20
10
Show member pathways
11.1 HADH HMGCL
11 10.87 BTD LMBRD1
12 10.82 HADH PC
13 10.78 LMBRD1 MMUT
14 9.73 BTD HLCS

GO Terms for Holocarboxylase Synthetase Deficiency

Cellular components related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.56 ACADL HADH HLCS HMGCL MMUT PC
2 mitochondrial matrix GO:0005759 9.1 ACADL BTD HADH HMGCL MMUT PC

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.56 ACADL HADH HMGCL PC
2 metabolic process GO:0008152 9.5 HLCS MTHFR PC
3 fatty acid beta-oxidation GO:0006635 9.4 ACADL HADH
4 gluconeogenesis GO:0006094 9.37 PC SLC25A13
5 cobalamin metabolic process GO:0009235 9.16 LMBRD1 MMUT
6 homocysteine metabolic process GO:0050667 8.96 MMUT MTHFR
7 biotin metabolic process GO:0006768 8.8 BTD HLCS PC

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

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.56 HLCS HMGCL MTHFR PC
2 fatty-acyl-CoA binding GO:0000062 9.32 ACADL HMGCL
3 cobalamin binding GO:0031419 9.16 LMBRD1 MMUT
4 modified amino acid binding GO:0072341 8.96 MMUT MTHFR
5 biotin binding GO:0009374 8.62 HLCS PC

Sources for Holocarboxylase Synthetase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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