CHOLESTEROL BIOSYNTHETIC PATHWAY (PW:0000454)
Description
The study of cholesterol spans decades of research and has
garnered several Nobel prizes. Cholesterol, a major end product of the
isoprenoid biosynthetic pathway, is an essential component of cell membranes
and lipid rafts and is the precursor for the synthesis of steroid hormones and
bile acids. Cholesterol is derived from diet or via de novo synthesis from acetyl-CoA. The biosynthetic pathway
requires some 30 reactions involving enzymes localized in the cytosol, ER membrane
and possibly peroxisomes. The biosynthesis of the 27-carbon molecule from the
initial 2-carbon acetyl-CoA building block involves the formation of mevalonate
in the rate-determining step of the reaction leading to the formation of IPP.
IPP is the substrate for the synthesis of sterols such as cholesterol and of
non-sterol isoprenoids used in a variety of cellular functions. Briefly described,
Acat2 interconverts acetyl-CoA and acetoacetyl-CoA which are condensed into
HMG-CoA by Hmgcs1. The reduction of HMG-CoA to mevalonate is catalyzed by
Hmgcr. The enzyme is the target of statin drugs acting as competitive
inhibitors. Mevalonate is phosphorylated twice sequentially by Mvk and Pmvk,
respectively; the mevalonate-PP product is decarboxylated and then dehydrated
by Mvd to yield IPP. IPP is kept in equilibrium with DMAPP by Idi1. Fdps
catalyzes the head-to-tail condensation of IPP and DMAPP to form GPP first, and
then of GPP and IPP to form FPP. Two molecules of FPP are condensed and then
reduced to form squalene by Fdft1 in the first committed sterol step in the
pathway. An oxygen-dependent step requiring FAD and NADPH followed by cyclization
reactions carried out by Sqle and Lss respectively, convert squalene to lanosterol.
Fdft1, Sqle and Lss enzymes are also targets for the development of cholesterol-lowering
drugs. As these enzymes act downstream of Hmgcr, drugs that inhibit their
function would not interfere with the production of IPP-derived non-sterol
compounds, as explained above (eg. dolichol, ubiquinone). The pathway from
lanosterol to cholesterol involves a series of demethylation, reduction and
oxidation reactions which may proceed via two alternative routes; the exact sequence
of events is still to be established. The availability of cholesterol is
tightly regulated by post-translational modifications, at the transcriptional
level and by feedback mechanisms - the role of the SREBP signaling pathway in the
control of cholesterol synthesis and transport is a notable example. High
levels of cholesterol are associated with cardiovascular diseases, hence the
targeting of biosynthetic enzymes for the development of drugs. On the other
hand, defects in some of the enzymes have been associated with a variety of
disorders and syndromes.
To see the Ontology
Report for annotations, GViewer and download click here [Click here to see the ontology report for associated GO
term - GO:0006695 and entry at Reactome - REACT_9405.2 ]...(less)
Pathway Diagram:
Genes in Pathway:
G
Acat2 acetyl-CoA acetyltransferase 2
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 1:47,695,833...47,713,879
G
Cyp51 cytochrome P450, family 51
ISO IDA SMPDB PMID:16876788 PMID:12668600 PMID:7581240 SMP:00023, RGD:2316857 , RGD:2316868 , RGD:2316902
NCBI chr 4:30,036,956...30,055,410
G
Dhcr24 24-dehydrocholesterol reductase
ISO SMPDB PMID:16876788 PMID:12668600 SMP:00023, RGD:2316857 , RGD:2316868
NCBI chr 5:121,344,552...121,371,124
G
Dhcr7 7-dehydrocholesterol reductase
ISO IMP RGD
PMID:16876788 PMID:12668600 PMID:9831636 RGD:2316857 , RGD:2316868 , RGD:2316918
NCBI chr 1:199,015,081...199,031,055
G
Ebp EBP, cholestenol delta-isomerase
ISO SMPDB PMID:16876788 PMID:12668600 SMP:00023, RGD:2316857 , RGD:2316868
NCBI chr X:14,299,427...14,305,826
G
Fdft1 farnesyl diphosphate farnesyl transferase 1
IMP ISO SMPDB PMID:16440058 PMID:16876788 SMP:00023, RGD:1626611 , RGD:2316857
NCBI chr15:37,412,143...37,440,198
G
Fdps farnesyl diphosphate synthase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 2:174,497,402...174,507,031
G
Ggps1 geranylgeranyl diphosphate synthase 1
ISO SMPDB SMP:00023
NCBI chr17:51,263,262...51,282,471
G
Hmgcr 3-hydroxy-3-methylglutaryl-CoA reductase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 2:27,997,523...28,018,983
G
Hmgcs1 3-hydroxy-3-methylglutaryl-CoA synthase 1
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 2:51,649,368...51,667,100
G
Hsd17b7 hydroxysteroid (17-beta) dehydrogenase 7
ISO SMPDB SMP:00023
NCBI chr13:82,170,079...82,190,018
G
Idi1 isopentenyl-diphosphate delta isomerase 1
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr17:61,629,592...61,637,357
G
Lbr lamin B receptor
ISO RGD
PMID:16876788 PMID:12668600 RGD:2316857 , RGD:2316868
NCBI chr13:93,539,386...93,564,026
G
Lipa lipase A, lysosomal acid type
ISO SMPDB SMP:00023
NCBI chr 1:232,024,351...232,057,735
G
Lss lanosterol synthase
IMP ISO IDA SMPDB PMID:16440058 PMID:16876788 PMID:1429550 SMP:00023, RGD:1626611 , RGD:2316857 , RGD:2316919
NCBI chr20:12,091,138...12,118,858
G
Msmo1 methylsterol monooxygenase 1
ISO SMPDB SMP:00023
NCBI chr16:24,980,680...24,997,927
G
Mvd mevalonate diphosphate decarboxylase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr19:50,496,366...50,506,429
G
Mvk mevalonate kinase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr12:42,141,391...42,158,893
G
Nsdhl NAD(P) dependent steroid dehydrogenase-like
ISO SMPDB PMID:16876788 PMID:12668600 SMP:00023, RGD:2316857 , RGD:2316868
NCBI chr X:150,775,034...150,807,161
G
Pmvk phosphomevalonate kinase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 2:174,876,586...174,886,365
G
Sc5d sterol-C5-desaturase
ISO IDA SMPDB PMID:16876788 PMID:12668600 PMID:7961720 SMP:00023, RGD:2316857 , RGD:2316868 , RGD:2316911
NCBI chr 8:42,629,649...42,641,257
G
Soat1 sterol O-acyltransferase 1
ISO SMPDB SMP:00023
NCBI chr13:68,552,274...68,597,529
G
Sqle squalene epoxidase
ISO SMPDB PMID:16876788 SMP:00023, RGD:2316857
NCBI chr 7:90,867,973...90,883,623
G
Tm7sf2 transmembrane 7 superfamily member 2
ISO SMPDB SMP:00023
NCBI chr 1:203,355,930...203,360,287
Pathway Gene Annotations
Disease Annotations Associated with Genes in the cholesterol biosynthetic pathway
Acat2 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome , arteriosclerosis , beta-ketothiolase deficiency , coronary artery disease , Cytosolic Acetoacetyl-CoA Thiolase Deficiency , Hypercholesterolemia , Metabolic Syndrome Cyp51 Antley-Bixler syndrome , cardiomyopathy , cataract , cerebral cavernous malformation , diabetes mellitus , Hypercholesterolemia , long QT syndrome , long QT syndrome 1 , long QT syndrome 11 , pleomorphic xanthoastrocytoma , Romano-Ward Syndrome Dhcr24 Alzheimer's disease , autism spectrum disorder , COVID-19 , Desmosterolosis , genetic disease , Hydrops Fetalis , lipid metabolism disorder , Q fever , schizophrenia Dhcr7 3-methylglutaconic aciduria type 7b , acute promyelocytic leukemia , Animal Disease Models , autistic disorder , Behcet's disease , cerebral folate receptor alpha deficiency , Developmental Disabilities , genetic disease , hepatoblastoma , intellectual disability , liver cirrhosis , Metabolic Bone Diseases , microcephaly , Muscle Hypotonia , primary microcephaly , Smith-Lemli-Opitz syndrome , Vitamin D Deficiency Ebp autistic disorder , autosomal recessive congenital ichthyosis , chondrodysplasia punctata , congenital disorder of glycosylation type IIm , connective tissue disease , Developmental Disease , genetic disease , immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome , MEND syndrome , neurodegeneration with brain iron accumulation 5 , syndromic X-linked intellectual disability Lubs type , Thrombocytopenia 1 , Wiskott-Aldrich syndrome , X-linked chondrodysplasia punctata 1 , X-linked chondrodysplasia punctata 2 , X-linked epilepsy with variable learning disabilities and behavior disorders , X-linked severe congenital neutropenia Fdft1 Atrioventricular Septal Defect 4 , cannabis abuse , cataract , Cocaine-Related Disorders , hepatocellular carcinoma , Neurodevelopmental Disorders , phencyclidine abuse , Squalene Synthase Deficiency , thoracic aortic aneurysm Fdps Charcot-Marie-Tooth disease type 2 , gastrointestinal stromal tumor , immunodeficiency 42 , MHC class II deficiency , parathyroid carcinoma , Porokeratosis 9, Multiple Types , Postmenopausal Osteoporosis , severe congenital neutropenia 3 , severe congenital neutropenia 5 Ggps1 Chediak-Higashi syndrome , common variable immunodeficiency 14 , gastrointestinal stromal tumor , MUSCULAR DYSTROPHY, CONGENITAL HEARING LOSS, AND OVARIAN INSUFFICIENCY SYNDROME , parathyroid carcinoma , sensorineural hearing loss , Tubular Aggregate Myopathies Hmgcr acute kidney failure , Acute Lung Injury , Alzheimer's disease , asthma , attention deficit hyperactivity disorder , autoimmune disease , Bacteremia , Brain Injuries , chronic kidney disease , coronary artery disease , Coronary Disease , dementia , diabetes mellitus , drug-induced hepatitis , end stage renal disease , Experimental Arthritis , Experimental Autoimmune Encephalomyelitis , Experimental Autoimmune Neuritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Gallstones , genetic disease , hepatocellular carcinoma , Huntington's disease , Hypercholesterolemia , Hyperlipoproteinemia Type II , intermediate coronary syndrome , limb-girdle muscular dystrophy , metabolic dysfunction-associated steatotic liver disease , Metabolic Syndrome , mevalonic aciduria , muscular disease , MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 28 , Neurodevelopmental Disorders , Parkinson's disease , premature menopause , pulmonary hypertension , Q fever , Reperfusion Injury , Sandhoff disease , Stroke , Surgical Wound Dehiscence , type 2 diabetes mellitus , uveitis , Wilson disease Hmgcs1 developmental and epileptic encephalopathy , early infantile epileptic encephalopathy , Experimental Diabetes Mellitus , Neurodevelopmental Disorders , obesity , rigid spine muscular dystrophy 1 , Spinal Cord Compression Hsd17b7 gastrointestinal stromal tumor , parathyroid carcinoma , polycystic ovary syndrome Lbr Anadysplasia-Like, Spontaneously Remitting Spondylometaphyseal Dysplasia , asphyxiating thoracic dystrophy , asphyxiating thoracic dystrophy 1 , connective tissue disease , gastrointestinal stromal tumor , genetic disease , Greenberg dysplasia , ichthyosis vulgaris , lymphopenia , parathyroid carcinoma , Pelger-Huet anomaly , PELGER-HUET ANOMALY WITH MILD SKELETAL ANOMALIES , primary biliary cholangitis , Retrognathia , Reynolds Syndrome , systemic lupus erythematosus Lipa autoimmune lymphoproliferative syndrome , cholesterol ester storage disease , coronary artery disease , COVID-19 , Familial Thoracic Aortic Aneurysm 6 , Fibrosis , lysosomal acid lipase deficiency , Niemann-Pick disease type C1 , Wolman disease , Wolman Disease with Hypolipoproteinemia and Acanthocytosis Lss alopecia-mental retardation syndrome 4 , autistic disorder , Axenfeld-Rieger syndrome type 3 , cataract , cataract 44 , cataract 9 multiple types , developmental and epileptic encephalopathy 30 , genetic disease , homocystinuria , Hypercholesterolemia , hypotrichosis 14 , lipid storage disease , primary ciliary dyskinesia , progressive myoclonus epilepsy , Q fever Msmo1 genetic disease , Microcephaly, Congenital Cataract, and Psoriasiform Dermatitis Mvd 16Q24.3 Microdeletion Syndrome , autosomal recessive chronic granulomatous disease 4 , Fanconi anemia , Hypercholesterolemia , KBG syndrome , porokeratosis , Porokeratosis 7, Multiple Types , primary ciliary dyskinesia 33 Mvk Arthralgia , Chediak-Higashi syndrome , ectodermal dysplasia 1 , exanthem , Fever , fundus dystrophy , genetic disease , hepatocellular carcinoma , hyperimmunoglobulinemia D periodic fever syndrome , Inflammation , lipid metabolism disorder , methylmalonic acidemia , methylmalonic acidemia cblB type , mevalonic aciduria , nemaline myopathy 5A , Porokeratosis 3, Multiple Types Nsdhl adrenoleukodystrophy , autistic disorder , autosomal hemophilia A , autosomal recessive congenital ichthyosis , Barth syndrome , Bloch-Sulzberger syndrome , cerebral creatine deficiency syndrome 1 , CHILD syndrome , CK syndrome , connective tissue disease , dyskeratosis congenita , Emery-Dreifuss muscular dystrophy , epilepsy , factor VIII deficiency , favism , genetic disease , head and neck squamous cell carcinoma , Hearing Loss , intellectual disability , paraplegia , periventricular nodular heterotopia , syndromic X-linked intellectual disability Lubs type , X-linked chondrodysplasia punctata 1 Pmvk Charcot-Marie-Tooth disease type 2 , gastrointestinal stromal tumor , genetic disease , immunodeficiency 42 , MHC class II deficiency , parathyroid carcinoma , porokeratosis , Porokeratosis 1, Multiple Types , severe congenital neutropenia 3 , severe congenital neutropenia 5 Sc5d CD3epsilon deficiency , chromosome 11 partial duplication syndrome , Dwarfism , genetic disease , immunodeficiency 17 , immunodeficiency 18 , immunodeficiency 19 , inflammatory bowel disease 28 , intellectual disability , isolated microphthalmia 5 , Lathosterolosis , liver disease , RASopathy , schizophrenia Soat1 1q24 Deletion Syndrome , aortic atherosclerosis , atherosclerosis , Chagas disease , Experimental Liver Cirrhosis , familial hyperlipidemia , gastrointestinal stromal tumor , hepatocellular carcinoma , parathyroid carcinoma , type 2 diabetes mellitus , xanthomatosis Sqle cholelithiasis , Experimental Liver Neoplasms , Hypercholesterolemia , obesity , trichorhinophalangeal syndrome type I Tm7sf2 Bardet-Biedl syndrome , glycogen storage disease V , high grade glioma , intellectual disability , leukocyte adhesion deficiency 3
16Q24.3 Microdeletion Syndrome Mvd 1q24 Deletion Syndrome Soat1 3-methylglutaconic aciduria type 7b Dhcr7 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Acat2 acute kidney failure Hmgcr Acute Lung Injury Hmgcr acute promyelocytic leukemia Dhcr7 adrenoleukodystrophy Nsdhl alopecia-mental retardation syndrome 4 Lss Alzheimer's disease Dhcr24 , Hmgcr Anadysplasia-Like, Spontaneously Remitting Spondylometaphyseal Dysplasia Lbr Animal Disease Models Dhcr7 Antley-Bixler syndrome Cyp51 aortic atherosclerosis Soat1 arteriosclerosis Acat2 Arthralgia Mvk asphyxiating thoracic dystrophy Lbr asphyxiating thoracic dystrophy 1 Lbr asthma Hmgcr atherosclerosis Soat1 Atrioventricular Septal Defect 4 Fdft1 attention deficit hyperactivity disorder Hmgcr autism spectrum disorder Dhcr24 autistic disorder Dhcr7 , Ebp , Lss , Nsdhl autoimmune disease Hmgcr autoimmune lymphoproliferative syndrome Lipa autosomal hemophilia A Nsdhl autosomal recessive chronic granulomatous disease 4 Mvd autosomal recessive congenital ichthyosis Ebp , Nsdhl Axenfeld-Rieger syndrome type 3 Lss Bacteremia Hmgcr Bardet-Biedl syndrome Tm7sf2 Barth syndrome Nsdhl Behcet's disease Dhcr7 beta-ketothiolase deficiency Acat2 Bloch-Sulzberger syndrome Nsdhl Brain Injuries Hmgcr cannabis abuse Fdft1 cardiomyopathy Cyp51 cataract Cyp51 , Fdft1 , Lss cataract 44 Lss cataract 9 multiple types Lss CD3epsilon deficiency Sc5d cerebral cavernous malformation Cyp51 cerebral creatine deficiency syndrome 1 Nsdhl cerebral folate receptor alpha deficiency Dhcr7 Chagas disease Soat1 Charcot-Marie-Tooth disease type 2 Fdps , Pmvk Chediak-Higashi syndrome Ggps1 , Mvk CHILD syndrome Nsdhl cholelithiasis Sqle cholesterol ester storage disease Lipa chondrodysplasia punctata Ebp chromosome 11 partial duplication syndrome Sc5d chronic kidney disease Hmgcr CK syndrome Nsdhl Cocaine-Related Disorders Fdft1 common variable immunodeficiency 14 Ggps1 congenital disorder of glycosylation type IIm Ebp connective tissue disease Ebp , Lbr , Nsdhl coronary artery disease Acat2 , Hmgcr , Lipa Coronary Disease Hmgcr COVID-19 Dhcr24 , Lipa Cytosolic Acetoacetyl-CoA Thiolase Deficiency Acat2 dementia Hmgcr Desmosterolosis Dhcr24 developmental and epileptic encephalopathy Hmgcs1 developmental and epileptic encephalopathy 30 Lss Developmental Disabilities Dhcr7 Developmental Disease Ebp diabetes mellitus Cyp51 , Hmgcr drug-induced hepatitis Hmgcr Dwarfism Sc5d dyskeratosis congenita Nsdhl early infantile epileptic encephalopathy Hmgcs1 ectodermal dysplasia 1 Mvk Emery-Dreifuss muscular dystrophy Nsdhl end stage renal disease Hmgcr epilepsy Nsdhl exanthem Mvk Experimental Arthritis Hmgcr Experimental Autoimmune Encephalomyelitis Hmgcr Experimental Autoimmune Neuritis Hmgcr Experimental Diabetes Mellitus Hmgcr , Hmgcs1 Experimental Liver Cirrhosis Hmgcr , Soat1 Experimental Liver Neoplasms Sqle factor VIII deficiency Nsdhl familial hyperlipidemia Soat1 Familial Thoracic Aortic Aneurysm 6 Lipa Fanconi anemia Mvd favism Nsdhl Fever Mvk Fibrosis Lipa fundus dystrophy Mvk Gallstones Hmgcr gastrointestinal stromal tumor Fdps , Ggps1 , Hsd17b7 , Lbr , Pmvk , Soat1 genetic disease Dhcr24 , Dhcr7 , Ebp , Hmgcr , Lbr , Lss , Msmo1 , Mvk , Nsdhl , Pmvk , Sc5d glycogen storage disease V Tm7sf2 Greenberg dysplasia Lbr head and neck squamous cell carcinoma Nsdhl Hearing Loss Nsdhl hepatoblastoma Dhcr7 hepatocellular carcinoma Fdft1 , Hmgcr , Mvk , Soat1 high grade glioma Tm7sf2 homocystinuria Lss Huntington's disease Hmgcr Hydrops Fetalis Dhcr24 Hypercholesterolemia Acat2 , Cyp51 , Hmgcr , Lss , Mvd , Sqle hyperimmunoglobulinemia D periodic fever syndrome Mvk Hyperlipoproteinemia Type II Hmgcr hypotrichosis 14 Lss ichthyosis vulgaris Lbr immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome Ebp immunodeficiency 17 Sc5d immunodeficiency 18 Sc5d immunodeficiency 19 Sc5d immunodeficiency 42 Fdps , Pmvk Inflammation Mvk inflammatory bowel disease 28 Sc5d intellectual disability Dhcr7 , Nsdhl , Sc5d , Tm7sf2 intermediate coronary syndrome Hmgcr isolated microphthalmia 5 Sc5d KBG syndrome Mvd Lathosterolosis Sc5d leukocyte adhesion deficiency 3 Tm7sf2 limb-girdle muscular dystrophy Hmgcr lipid metabolism disorder Dhcr24 , Mvk lipid storage disease Lss liver cirrhosis Dhcr7 liver disease Sc5d long QT syndrome Cyp51 long QT syndrome 1 Cyp51 long QT syndrome 11 Cyp51 lymphopenia Lbr lysosomal acid lipase deficiency Lipa MEND syndrome Ebp Metabolic Bone Diseases Dhcr7 metabolic dysfunction-associated steatotic liver disease Hmgcr Metabolic Syndrome Acat2 , Hmgcr methylmalonic acidemia Mvk methylmalonic acidemia cblB type Mvk mevalonic aciduria Hmgcr , Mvk MHC class II deficiency Fdps , Pmvk microcephaly Dhcr7 Microcephaly, Congenital Cataract, and Psoriasiform Dermatitis Msmo1 Muscle Hypotonia Dhcr7 muscular disease Hmgcr MUSCULAR DYSTROPHY, CONGENITAL HEARING LOSS, AND OVARIAN INSUFFICIENCY SYNDROME Ggps1 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 28 Hmgcr nemaline myopathy 5A Mvk neurodegeneration with brain iron accumulation 5 Ebp Neurodevelopmental Disorders Fdft1 , Hmgcr , Hmgcs1 Niemann-Pick disease type C1 Lipa obesity Hmgcs1 , Sqle paraplegia Nsdhl parathyroid carcinoma Fdps , Ggps1 , Hsd17b7 , Lbr , Pmvk , Soat1 Parkinson's disease Hmgcr Pelger-Huet anomaly Lbr PELGER-HUET ANOMALY WITH MILD SKELETAL ANOMALIES Lbr periventricular nodular heterotopia Nsdhl phencyclidine abuse Fdft1 pleomorphic xanthoastrocytoma Cyp51 polycystic ovary syndrome Hsd17b7 porokeratosis Mvd , Pmvk Porokeratosis 1, Multiple Types Pmvk Porokeratosis 3, Multiple Types Mvk Porokeratosis 7, Multiple Types Mvd Porokeratosis 9, Multiple Types Fdps Postmenopausal Osteoporosis Fdps premature menopause Hmgcr primary biliary cholangitis Lbr primary ciliary dyskinesia Lss primary ciliary dyskinesia 33 Mvd primary microcephaly Dhcr7 progressive myoclonus epilepsy Lss pulmonary hypertension Hmgcr Q fever Dhcr24 , Hmgcr , Lss RASopathy Sc5d Reperfusion Injury Hmgcr Retrognathia Lbr Reynolds Syndrome Lbr rigid spine muscular dystrophy 1 Hmgcs1 Romano-Ward Syndrome Cyp51 Sandhoff disease Hmgcr schizophrenia Dhcr24 , Sc5d sensorineural hearing loss Ggps1 severe congenital neutropenia 3 Fdps , Pmvk severe congenital neutropenia 5 Fdps , Pmvk Smith-Lemli-Opitz syndrome Dhcr7 Spinal Cord Compression Hmgcs1 Squalene Synthase Deficiency Fdft1 Stroke Hmgcr Surgical Wound Dehiscence Hmgcr syndromic X-linked intellectual disability Lubs type Ebp , Nsdhl systemic lupus erythematosus Lbr thoracic aortic aneurysm Fdft1 Thrombocytopenia 1 Ebp trichorhinophalangeal syndrome type I Sqle Tubular Aggregate Myopathies Ggps1 type 2 diabetes mellitus Hmgcr , Soat1 uveitis Hmgcr Vitamin D Deficiency Dhcr7 Wilson disease Hmgcr Wiskott-Aldrich syndrome Ebp Wolman disease Lipa Wolman Disease with Hypolipoproteinemia and Acanthocytosis Lipa X-linked chondrodysplasia punctata 1 Ebp , Nsdhl X-linked chondrodysplasia punctata 2 Ebp X-linked epilepsy with variable learning disabilities and behavior disorders Ebp X-linked severe congenital neutropenia Ebp xanthomatosis Soat1
