MCID: HLC001
MIFTS: 58

Holocarboxylase Synthetase Deficiency

Categories: Genetic diseases, Rare diseases, Skin diseases, Metabolic 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 exanthema, lethargy and seizures. 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 irritability and keratoconjunctivitis

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.

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.

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

Wikipedia : 76 Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to... more...

Related Diseases for Holocarboxylase Synthetase Deficiency

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

UMLS symptoms related to Holocarboxylase Synthetase Deficiency:


exanthema, lethargy, seizures, vomiting

MGI Mouse Phenotypes related to Holocarboxylase Synthetase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.96 SLC25A20 ACADL AGL BTD HADH HMGCL
2 cardiovascular system MP:0005385 9.87 PTS SLC25A20 ACADL HMGCL LMBRD1 MUT
3 mortality/aging MP:0010768 9.65 ACADL AGL HMGCL LMBRD1 MTHFR MUT
4 liver/biliary system MP:0005370 9.63 ACADL AGL HMGCL MUT SLC25A13 SLC25A20
5 renal/urinary system MP:0005367 9.1 ACADL BTD HADH MUT 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 Micronutrients Not Applicable
4 Trace Elements Not Applicable
5 Vitamin B Complex Not Applicable
6 Vitamins Not Applicable
7 Folate Nutraceutical Not Applicable
8 Vitamin B7 Nutraceutical Not Applicable
9 Vitamin B9 Nutraceutical 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 Biotin Deficiency and Restless Legs Syndrome Completed NCT02011191 Not Applicable
4 BIOtinidase Test In Optic-Neuropathy Recruiting NCT03268681

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 50)
# 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
Susceptibility to heat stress and aberrant gene expression patterns in holocarboxylase synthetase-deficient Drosophila melanogaster are caused by decreased biotinylation of histones, not of carboxylases. ( 17374649 )
2007
15
Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands. ( 17417720 )
2007
16
[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
17
Holocarboxylase synthetase deficiency presenting as ichthyosis. ( 16650223 )
2006
18
Holocarboxylase synthetase deficiency: report of one case. ( 17407983 )
2006
19
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. ( 16027709 )
2005
20
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. ( 16231399 )
2005
21
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. ( 12855220 )
2003
22
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. ( 12633764 )
2003
23
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. ( 12124727 )
2002
24
[Holocarboxylase synthetase deficiency]. ( 11462701 )
2001
25
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. ( 11735028 )
2001
26
Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation. ( 10770035 )
2000
27
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. ( 11185745 )
2000
28
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. ( 11196112 )
2000
29
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. ( 10653324 )
2000
30
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. ( 10437643 )
1999
31
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. ( 10234606 )
1999
32
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. ( 10190325 )
1999
33
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. ( 10590022 )
1999
34
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. ( 10215065 )
1999
35
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. ( 9686819 )
1998
36
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. ( 9645047 )
1998
37
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. ( 9758715 )
1998
38
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. ( 9870216 )
1998
39
Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency. ( 9183268 )
1997
40
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate. ( 8814349 )
1996
41
Late-onset holocarboxylase synthetase deficiency. ( 8982946 )
1996
42
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. ( 8541348 )
1995
43
Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy. ( 8006369 )
1994
44
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. ( 8319716 )
1993
45
Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. ( 2515372 )
1989
46
A new case of holocarboxylase synthetase deficiency. ( 2515377 )
1989
47
Biotin holocarboxylase synthetase deficiency. ( 3860175 )
1985
48
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. ( 6811711 )
1982
49
Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. ( 7226522 )
1981
50
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 221)
# 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_000411.6(HLCS): c.1711G> A (p.Asp571Asn) single nucleotide variant Pathogenic rs119103228 GRCh37 Chromosome 21, 38132112: 38132112
5 HLCS NM_000411.6(HLCS): c.1711G> A (p.Asp571Asn) single nucleotide variant Pathogenic 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 rs119103231 GRCh37 Chromosome 21, 38137345: 38137345
11 HLCS NM_000411.6(HLCS): c.1648G> A (p.Val550Met) single nucleotide variant Pathogenic rs119103231 GRCh38 Chromosome 21, 36765044: 36765044
12 HLCS NM_000411.7(HLCS): c.1519+5G> A single nucleotide variant Pathogenic rs753887925 GRCh38 Chromosome 21, 36767213: 36767213
13 HLCS NM_000411.7(HLCS): c.1519+5G> A single nucleotide variant 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 Pathogenic rs28934602 GRCh37 Chromosome 21, 38309098: 38309098
17 HLCS NM_000411.6(HLCS): c.647T> G (p.Leu216Arg) single nucleotide variant Pathogenic rs28934602 GRCh38 Chromosome 21, 36936798: 36936798
18 HLCS NM_000411.7(HLCS): c.1624C> T (p.Gln542Ter) single nucleotide variant Pathogenic rs794727957 GRCh37 Chromosome 21, 38137369: 38137369
19 HLCS NM_000411.7(HLCS): c.1624C> T (p.Gln542Ter) single nucleotide variant Pathogenic rs794727957 GRCh38 Chromosome 21, 36765068: 36765068
20 HLCS NM_000411.6(HLCS): c.2059G> A (p.Val687Ile) single nucleotide variant Uncertain significance rs145648338 GRCh38 Chromosome 21, 36754368: 36754368
21 HLCS NM_000411.6(HLCS): c.2059G> A (p.Val687Ile) single nucleotide variant Uncertain significance rs145648338 GRCh37 Chromosome 21, 38126669: 38126669
22 HLCS NM_000411.7(HLCS): c.1921G> A (p.Val641Met) single nucleotide variant Benign/Likely benign rs150665851 GRCh38 Chromosome 21, 36756630: 36756630
23 HLCS NM_000411.7(HLCS): c.1921G> A (p.Val641Met) single nucleotide variant Benign/Likely benign rs150665851 GRCh37 Chromosome 21, 38128931: 38128931
24 HLCS NM_000411.6(HLCS): c.1672G> A (p.Glu558Lys) single nucleotide variant Benign/Likely benign rs149736764 GRCh37 Chromosome 21, 38137321: 38137321
25 HLCS NM_000411.6(HLCS): c.1672G> A (p.Glu558Lys) single nucleotide variant Benign/Likely benign rs149736764 GRCh38 Chromosome 21, 36765020: 36765020
26 HLCS NM_000411.6(HLCS): c.890G> A (p.Arg297Gln) single nucleotide variant Uncertain significance rs146030669 GRCh37 Chromosome 21, 38308855: 38308855
27 HLCS NM_000411.6(HLCS): c.890G> A (p.Arg297Gln) single nucleotide variant Uncertain significance rs146030669 GRCh38 Chromosome 21, 36936555: 36936555
28 HLCS NM_000411.6(HLCS): c.782delG (p.Gly261Valfs) deletion Pathogenic rs771944310 GRCh38 Chromosome 21, 36936663: 36936663
29 HLCS NM_000411.6(HLCS): c.782delG (p.Gly261Valfs) deletion Pathogenic rs771944310 GRCh37 Chromosome 21, 38308963: 38308963
30 HLCS NM_000411.6(HLCS): c.632C> T (p.Thr211Met) single nucleotide variant Conflicting interpretations of pathogenicity rs142524025 GRCh38 Chromosome 21, 36936813: 36936813
31 HLCS NM_000411.6(HLCS): c.632C> T (p.Thr211Met) single nucleotide variant Conflicting interpretations of pathogenicity rs142524025 GRCh37 Chromosome 21, 38309113: 38309113
32 HLCS NM_000411.6(HLCS): c.561C> T (p.Ala187=) single nucleotide variant Benign rs116114362 GRCh38 Chromosome 21, 36936884: 36936884
33 HLCS NM_000411.6(HLCS): c.561C> T (p.Ala187=) single nucleotide variant Benign rs116114362 GRCh37 Chromosome 21, 38309184: 38309184
34 HLCS NM_000411.6(HLCS): c.473C> T (p.Thr158Met) single nucleotide variant Benign/Likely benign rs112176097 GRCh38 Chromosome 21, 36936972: 36936972
35 HLCS NM_000411.6(HLCS): c.473C> T (p.Thr158Met) single nucleotide variant Benign/Likely benign rs112176097 GRCh37 Chromosome 21, 38309272: 38309272
36 HLCS NM_000411.6(HLCS): c.-254C> T single nucleotide variant Conflicting interpretations of pathogenicity rs149104163 GRCh37 Chromosome 21, 38318451: 38318451
37 HLCS NM_000411.6(HLCS): c.-254C> T single nucleotide variant Conflicting interpretations of pathogenicity rs149104163 GRCh38 Chromosome 21, 36946151: 36946151
38 HLCS NM_000411.6(HLCS): c.*40A> G single nucleotide variant Likely benign rs77014096 GRCh37 Chromosome 21, 38126507: 38126507
39 HLCS NM_000411.6(HLCS): c.*40A> G single nucleotide variant Likely benign rs77014096 GRCh38 Chromosome 21, 36754206: 36754206
40 HLCS NM_000411.6(HLCS): c.*3247A> G single nucleotide variant Uncertain significance rs114061673 GRCh37 Chromosome 21, 38123300: 38123300
41 HLCS NM_000411.6(HLCS): c.*3247A> G single nucleotide variant Uncertain significance rs114061673 GRCh38 Chromosome 21, 36750999: 36750999
42 HLCS NM_000411.6(HLCS): c.*3226delT deletion Uncertain significance rs886057058 GRCh37 Chromosome 21, 38123321: 38123321
43 HLCS NM_000411.6(HLCS): c.*3226delT deletion Uncertain significance rs886057058 GRCh38 Chromosome 21, 36751020: 36751020
44 HLCS NM_000411.6(HLCS): c.*3209C> T single nucleotide variant Uncertain significance rs886057059 GRCh38 Chromosome 21, 36751037: 36751037
45 HLCS NM_000411.6(HLCS): c.*3209C> T single nucleotide variant Uncertain significance rs886057059 GRCh37 Chromosome 21, 38123338: 38123338
46 HLCS NM_000411.6(HLCS): c.*2945C> T single nucleotide variant Uncertain significance rs71332549 GRCh38 Chromosome 21, 36751301: 36751301
47 HLCS NM_000411.6(HLCS): c.*2945C> T single nucleotide variant Uncertain significance rs71332549 GRCh37 Chromosome 21, 38123602: 38123602
48 HLCS NM_000411.6(HLCS): c.*2624G> A single nucleotide variant Uncertain significance rs73210780 GRCh38 Chromosome 21, 36751622: 36751622
49 HLCS NM_000411.6(HLCS): c.*2624G> A single nucleotide variant Uncertain significance rs73210780 GRCh37 Chromosome 21, 38123923: 38123923
50 HLCS NM_000411.6(HLCS): c.*2545C> A single nucleotide variant Uncertain significance rs180866987 GRCh38 Chromosome 21, 36751701: 36751701

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 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.07 ACADL AGL BTD HADH HLCS HMGCL
2
Show member pathways
12.57 ACADL HADH HMGCL MUT SLC25A20
3
Show member pathways
12.04 BTD HLCS LMBRD1 MTHFR MUT PC
4
Show member pathways
12.01 MTHFR MUT PC
5
Show member pathways
11.68 HADH HMGCL MUT
6 11.42 HADH HMGCL MUT PC
7
Show member pathways
11.36 ACADL HADH MUT
8
Show member pathways
11.22 ACADL HADH SLC25A20
9
Show member pathways
11.1 HADH HMGCL
10 10.87 BTD LMBRD1
11 10.82 HADH PC
12 10.78 LMBRD1 MUT
13 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 9.61 ACADL HADH HLCS HMGCL MUT PC
2 mitochondrial inner membrane GO:0005743 9.46 HADH HMGCL SLC25A13 SLC25A20
3 mitochondrial matrix GO:0005759 9.1 ACADL BTD HADH HMGCL MUT 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 9.62 ACADL HADH HMGCL PC
2 fatty acid beta-oxidation GO:0006635 9.43 ACADL HADH
3 metabolic process GO:0008152 9.43 ACADL AGL HLCS MTHFR MUT PC
4 gluconeogenesis GO:0006094 9.4 PC SLC25A13
5 cellular amino acid metabolic process GO:0006520 9.37 MTHFR PTS
6 cobalamin metabolic process GO:0009235 9.26 LMBRD1 MUT
7 homocysteine metabolic process GO:0050667 9.16 MTHFR MUT
8 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 MUT
4 modified amino acid binding GO:0072341 8.96 MTHFR MUT
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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