CYP27A1

Summary

CYP27A1 (cytochrome P450 family 27 subfamily A member 1, HGNC:2605) is a protein-coding gene on chromosome 2q35, encoding Sterol 26-hydroxylase, mitochondrial (Q02318). Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein oxidizes cholesterol intermediates as part of the bile synthesis pathway. Since the conversion of cholesterol to bile acids is the major route for removing cholesterol from the body, this protein is important for overall cholesterol homeostasis. Mutations in this gene cause cerebrotendinous xanthomatosis, a rare autosomal recessive lipid storage disease.

Source: NCBI Gene 1593 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebrotendinous xanthomatosis (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 1,253 total — 102 pathogenic, 68 likely-pathogenic
• Phenotypes (HPO): 115
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2605
Approved symbol	CYP27A1
Name	cytochrome P450 family 27 subfamily A member 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	CTX, CP27
Ensembl gene	ENSG00000135929
Ensembl biotype	protein_coding
OMIM	606530
Entrez	1593

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000258415, ENST00000411688, ENST00000445971, ENST00000466602, ENST00000494263, ENST00000901552, ENST00000901553, ENST00000901554, ENST00000901555, ENST00000901556, ENST00000901557, ENST00000901558, ENST00000901559, ENST00000901560, ENST00000901561, ENST00000901562, ENST00000901563, ENST00000901564

RefSeq mRNA: 1 — MANE Select: NM_000784 NM_000784

CCDS: CCDS2423

Canonical transcript exons

ENST00000258415 — 9 exons

Exon	Start	End
ENSE00000785876	218814021	218814187
ENSE00000785877	218814380	218814458
ENSE00000785878	218814545	218814757
ENSE00001838541	218814911	218815293
ENSE00001902442	218782147	218782437
ENSE00003532282	218812222	218812421
ENSE00003588364	218809577	218809767
ENSE00003613720	218812552	218812749
ENSE00003673358	218812924	218813096

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5640 / max 1453.7930, expressed in 1222 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25395	19.1754	813
25396	9.4407	491
25393	5.6389	1072
25392	0.6337	378
25394	0.5536	152
25391	0.1217	48

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.22	gold quality
liver	UBERON:0002107	98.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.71	gold quality
spinal cord	UBERON:0002240	95.72	gold quality
right adrenal gland cortex	UBERON:0035827	95.17	gold quality
right adrenal gland	UBERON:0001233	94.99	gold quality
tibial nerve	UBERON:0001323	94.95	gold quality
granulocyte	CL:0000094	94.83	gold quality
left adrenal gland	UBERON:0001234	94.59	gold quality
left adrenal gland cortex	UBERON:0035825	94.55	gold quality
upper lobe of left lung	UBERON:0008952	94.48	gold quality
mucosa of transverse colon	UBERON:0004991	94.47	gold quality
right uterine tube	UBERON:0001302	94.35	gold quality
adrenal cortex	UBERON:0001235	94.24	gold quality
duodenum	UBERON:0002114	94.18	gold quality
monocyte	CL:0000576	94.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.94	gold quality
right lung	UBERON:0002167	93.85	gold quality
upper lobe of lung	UBERON:0008948	93.83	gold quality
descending thoracic aorta	UBERON:0002345	93.70	gold quality
inferior vagus X ganglion	UBERON:0005363	93.56	gold quality
jejunal mucosa	UBERON:0000399	93.55	gold quality
mucosa of stomach	UBERON:0001199	93.41	gold quality
leukocyte	CL:0000738	93.31	gold quality
small intestine	UBERON:0002108	93.29	gold quality
minor salivary gland	UBERON:0001830	93.21	gold quality
pigmented layer of retina	UBERON:0001782	93.19	gold quality
retina	UBERON:0000966	93.17	gold quality
mononuclear cell	CL:0000842	93.15	gold quality
medial globus pallidus	UBERON:0002477	93.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	506.35
E-CURD-122	yes	69.05
E-GEOD-135922	yes	18.92
E-ENAD-20	no	1021.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, ETS2, HNF1A, HNF4A, IRF6, NR0B2, NR3C1, PPARA, PPARG, SP1, SP3, TBP, TOX, USF1

miRNA regulators (miRDB)

17 targeting CYP27A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-2114-5P	96.00	64.56	617
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-6823-3P	95.45	66.14	704

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A Japanese patient with cerebrotendinous xanthomatosis has different mutations within two functional domains of CYP27. (PMID:11903362)
• regulation of CYP7A1 and CYP27A1 in human liver (PMID:12011083)
• Endogenous CYP27A1 is of importance for the normal efflux of both cholesterol and cholestanol from tendons. (PMID:12117727)
• levels of 27-hydroxycholesterol are not of critical importance for cholesterol homeostasis in mice. (PMID:12119285)
• A compound heterozygous mutation in CYP27A1 (one missense mutation and one intronic nucleotide change) occurs in a Taiwanese family with cerebrotendinous xanthomatosis. (PMID:12242561)
• The very high activity of CYP27A1 towards the cholestanol precursor 4-cholesten-3-one may be of importance in connection with the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis (PMID:12777473)
• The pathogenesis of cholesterolosis may be multifactorial, but is not caused by reduced efflux of cholesterol due to a defect sterol 27-hydroxylase mechanism. (PMID:14672608)
• We reported a Hong Kong Chinese proband with Cerebrotendinous Xanthomatosis in which a novel acceptor splicing site mutation (IVS6-1G>T) was identified. (PMID:14741198)
• nuclear receptor-regulated CYP27 expression is likely to be a key integrator of retinoic acid receptor-PPARgamma-LXR signaling, relying on natural ligands and contributing to lipid metabolism in macrophages (PMID:15340076)
• stimulation of CYP27A1 by PPARgamma may represent a key previously unrecognized mechanism by which PPARgamma protects against atherosclerosis (PMID:15533057)
• Data suggest that induction of sterol 27-hydroxylase (CYP27A1) by TGF-beta1 may be responsible for some of the anti-atherogenic properties of this cytokine. (PMID:15708352)
• In this study showed that the Cerebrotendinous xanthomatosis( CTX) due to CYP27 mutation R362C. (PMID:16157755)
• Mutation in Cytochrome P-450 CYP27A1 is associated with cerebrotendinous xanthomatosis (PMID:16372260)
• Mutation of the overlapping substrate-contact residues (W100, H103, T110, M301C, V367, I481, and V482) affected CYP27A1 binding and enzyme activity in a substrate-dependent manner and allowed identification of several important side chains. (PMID:16584175)
• Monocyte-derived cells express CYP27A1 and convert vitamin D3 into its active metabolite (PMID:16930540)
• there may be an intestine-specific PXR/CYP27A1/LXRalpha pathway that regulates intestine cholesterol efflux and HDL assembly. (PMID:17088262)
• Glutamine 85 cyp27A1 plays essential roles in both substrate-binding and protein folding. (PMID:17292862)
• human CYP27A1 gene is a target for estrogens and androgens (PMID:17482558)
• K226R, D321G, and P408S mutants showed 25-hydroxylation activity for 1alphaOHD(3) as well as wild type. (PMID:17697869)
• CYP27A1 and CYP24 expression is a function of malignant transformation in the colon (PMID:17875655)
• We found the first cerebrotendinous xanthomatosis family from Argentina with a new mutation in CYP27A1 gene. (PMID:18227423)
• Results describe the membrane topology of CYPs 27A1 and 11A1. (PMID:18791760)
• Single nucleotide polymorphisms may be associated with risk of prostate cancer in men with low vitamin D status. (PMID:19255064)
• Overexpression of CYP27A1 in CHOP cells decreased progesterone conversion to 20alpha-DH-progesterone in a dose-dependent manner (PMID:19671838)
• down-regulation of genes involved in the cholesterol synthesis pathway results in down-regulation of CYP27A1 which diminishes oxysterol concentrations (PMID:20149624)
• Four novel mutations located in different exons, in particular in the region of exons 2-5 of the CYP27A1 gene, present as classical cerebrotendinous xanthomatosis. (PMID:20402754)
• There needs to be a high level of suspicion of cerebrotendinous xanthomatosis (CXT) for any child with cataracts and developmental delay (PMID:20450308)
• An Arg104Gln mutation in sterol 27-hydroxylase is identified in Japanese patients with cerebrotendinous xanthomatosis; case 1 is a compound heterozygote for Arg104Gln in exon 2 and Arg441Gln in exon 8. (PMID:20558929)
• The average P450 concentrations/mg of total tissue protein were 345 fmol of CYP46A1 and 110 fmol of CYP27A1 in the temporal lobe, and 60 fmol of CYP46A1 and 490 fmol of CYP27A1 in the retina. (PMID:21049985)
• results indicate involvement of the JNK/c-jun pathway in AR-mediated upregulation of CYP27A1. The link to JNK signaling is interesting since inflammatory processes may upregulate CYP27A1 to clear cholesterol from peripheral tissues. (PMID:21134350)
• study found that adenosine A2A receptor stimulation inhibited foam cell formation by a mechanism dependent on the expression of CYP27A1 (PMID:21258856)
• Sterol 27-hydroxylase cytochrome P450 27A1 (CYP27A1) is involved in elimination of 7-ketocholesterol from the retinal pigment epithelium. (PMID:21411718)
• the post-translational modifications identified in CYP27A1 exemplify a general mechanism whereby oxidative stress and inflammation deleteriously affect protein function (PMID:21498512)
• Mutations consisting of c.1146_1151deletion-insertion and c.1214G>A substitution of CYP27A1 are identified in patients having cerebrotendinous xanthomatosis. (PMID:21958693)
• CYP27A1 mutations were found in the proband and a Chinese family with Cerebrotendinous Xanthomatosis (PMID:22018287)
• An alternative to elimination of brain cholesterol by the CYP46A1 mechanism is elimination by CYP27A1. (PMID:22185844)
• Features of the retinal environment which affect the activities and product profile of cholesterol-metabolizing cytochromes P450 CYP27A1 and CYP11A1. (PMID:22227097)
• This study has identified candidate genes for sporadic Amyotrophic lateral sclerosis( ALS), most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS . (PMID:22509407)
• The increased cutaneous CYP27B1 levels in the CKD patients suggest that the loss of renal activity of this enzyme is at least partially compensated for by the skin. (PMID:24029861)
• Cyp27A1 mutations were identified in early onset CAD pedigree. (PMID:24080357)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp27a1.1	ENSDARG00000033802
danio_rerio	cyp27a1.4	ENSDARG00000055159
danio_rerio	cyp27a1.2	ENSDARG00000069186
danio_rerio	CYP27A1	ENSDARG00000088013
mus_musculus	Cyp27a1	ENSMUSG00000026170
rattus_norvegicus	Cyp27a1	ENSRNOG00000017188
drosophila_melanogaster	sad	FBGN0003312

Paralogs (3): CYP24A1 (ENSG00000019186), CYP27B1 (ENSG00000111012), CYP27C1 (ENSG00000186684)

Protein

Protein identifiers

Sterol 26-hydroxylase, mitochondrial — Q02318 (reviewed: Q02318)

Alternative names: 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase, Cytochrome P-450C27/25, Cytochrome P450 27, Sterol 27-hydroxylase, Vitamin D(3) 25-hydroxylase

All UniProt accessions (3): C9J1K5, Q02318, F8WD90

UniProt curated annotations — full annotation on UniProt →

Function. Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid. Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the ’neutral’ (classic) and the ‘acid’ (alternative) pathways. May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism. Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form.

Subunit / interactions. Interacts with HSP70; this interaction is required for initial targeting to mitochondria.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed in the neural retina and underlying retinal pigment epithelium (at protein level). Expressed in the gray and white matter of cerebellum (at protein level).

Disease relevance. Cerebrotendinous xanthomatosis (CTX) [MIM:213700] Rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Hormone biosynthesis; cholecalciferol biosynthesis. Steroid metabolism; cholesterol degradation. Lipid metabolism; bile acid biosynthesis.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000775* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050479	CYP11_CYP27_families	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.15.15 — cholestanetriol 26-monooxygenase (BRENDA: 7 organisms, 53 substrates, 23 inhibitors, 9 Km, 10 kcat entries)
• EC 1.14.99.38 — cholesterol 25-monooxygenase (BRENDA: 12 organisms, 12 substrates, 2 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5BETA-CHOLESTANE-3ALPHA,7ALPHA,12ALPHA-TRIOL	0.0045–0.06	4
(24S)-3BETA-HYDROXY-24-METHYL-5ALPHA-CHOLESTA-8(	0.017	1
3BETA-HYDROXY-5ALPHA-CHOLEST-8(14)-EN-15-ONE	0.0047	1
5BETA-CHOLESTANE-3ALPHA,7ALPHA-DIOL	0.01	1
1ALPHA-HYDROXYVITAMIN D3	—	0
CHOLESTEROL	—	0
LUMISTEROL3	—	0

Catalyzed reactions (Rhea), 12 shown:

• 5beta-cholestane-3alpha,7alpha,12alpha-triol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol + 2 oxidized [adrenodoxin] + H2O (RHEA:14373)
• (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + 2 reduced [adrenodoxin] + O2 + H(+) = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + 2 oxidized [adrenodoxin] + H2O (RHEA:34627)
• 5beta-cholestane-3alpha,7alpha,12alpha-triol + 6 reduced [adrenodoxin] + 3 O2 + 5 H(+) = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + 6 oxidized [adrenodoxin] + 4 H2O (RHEA:34631)
• (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:40231)
• (25R)-3beta-hydroxy-5-cholesten-26-al + 2 reduced [adrenodoxin] + O2 + H(+) = (25R)-3beta-hydroxy-5-cholestenoate + 2 oxidized [adrenodoxin] + H2O (RHEA:45236)
• (25R)-cholest-5-ene-3beta,26-diol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-3beta-hydroxy-5-cholesten-26-al + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:46092)
• 2 reduced [adrenodoxin] + cholesterol + O2 + 2 H(+) = (25R)-cholest-5-ene-3beta,26-diol + 2 oxidized [adrenodoxin] + H2O (RHEA:46400)
• 4beta-hydroxycholesterol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-4beta,26-dihydroxycholesterol + 2 oxidized [adrenodoxin] + H2O (RHEA:46428)
• (25R)-4beta,26-dihydroxycholesterol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-3beta,4beta-dihydroxycholest-5-en-26-al + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:46432)
• (25R)-3beta,4beta-dihydroxycholest-5-en-26-al + 2 reduced [adrenodoxin] + O2 + H(+) = (25R)-3beta,4beta-dihydroxycholest-5-en-26-oate + 2 oxidized [adrenodoxin] + H2O (RHEA:46436)
• calciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = calcidiol + 2 oxidized [adrenodoxin] + H2O (RHEA:46588)
• 7-oxocholesterol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (25R)-3beta,26-dihydroxycholest-5-en-7-one + 2 oxidized [adrenodoxin] + H2O (RHEA:47344)

UniProt features (27 total): sequence variant 9, mutagenesis site 8, sequence conflict 3, modified residue 3, transit peptide 1, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02318-F1	89.02	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 476 (axial binding residue)

Post-translational modifications (3): 283, 509, 520

Mutagenesis-validated functional residues (8):

Position	Phenotype
240	impairs sterol 26-hydroxylase activity; when associated with a-244 and a-248.
240	impairs sterol 26-hydroxylase activity.
244	impairs sterol 26-hydroxylase activity; when associated with a-240 and a-248.
244	impairs sterol 26-hydroxylase activity.
248	impairs sterol 26-hydroxylase activity; when associated with a-240 and a-244.
248	impairs sterol 26-hydroxylase activity; confers demethylase activity.
268	reduces sterol 26-hydroxylase activity.
271	reduces sterol 26-hydroxylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193775	Synthesis of bile acids and bile salts via 24-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-211976	Endogenous sterols
R-HSA-5578996	Defective CYP27A1 causes CTX

MSigDB gene sets: 479 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, GNF2_HPN, GOBP_POLYOL_METABOLIC_PROCESS, REACTOME_ENDOGENOUS_STEROLS, MODULE_128, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, HOSHIDA_LIVER_CANCER_SUBCLASS_S3

GO Biological Process (12): bile acid biosynthetic process (GO:0006699), cholesterol catabolic process (GO:0006707), cholesterol metabolic process (GO:0008203), sterol metabolic process (GO:0016125), calcitriol biosynthetic process from calciol (GO:0036378), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), lipid biosynthetic process (GO:0008610), vitamin D metabolic process (GO:0042359), small molecule biosynthetic process (GO:0044283)

GO Molecular Function (10): iron ion binding (GO:0005506), steroid hydroxylase activity (GO:0008395), heme binding (GO:0020037), vitamin D 25-hydroxylase activity (GO:0030343), cholesterol 26-hydroxylase activity (GO:0031073), cholestanetetraol 26-dehydrogenase activity (GO:0047748), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	3
Cytochrome P450 - arranged by substrate type	1
Metabolic disorders of biological oxidation enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	3
small molecule metabolic process	2
lipid metabolic process	2
biosynthetic process	2
steroid hydroxylase activity	2
oxidoreductase activity	2
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
cholesterol metabolic process	1
sterol catabolic process	1
alcohol catabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
vitamin D biosynthetic process	1
polyol biosynthetic process	1
vitamin D3 metabolic process	1
primary metabolic process	1
lipid biosynthetic process	1
transition metal ion binding	1
monooxygenase activity	1
tetrapyrrole binding	1
calcitriol biosynthetic process from calciol	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP27A1	CYP7A1	P22680	945
CYP27A1	FDX1	P10109	870
CYP27A1	FDXR	P22570	833
CYP27A1	NR1H4	Q96RI1	830
CYP27A1	NR0B2	Q15466	816
CYP27A1	BGLAP	P02818	791
CYP27A1	VSIG2	Q96IQ7	784
CYP27A1	GPA33	Q99795	766
CYP27A1	PTH	P01270	759
CYP27A1	HMGCR	P04035	759
CYP27A1	NR5A2	O00482	739
CYP27A1	ABCB11	O95342	721
CYP27A1	SREBF1	P36956	690
CYP27A1	HSF4	Q9ULV5	685
CYP27A1	SLC10A1	Q14973	679

IntAct

11 interactions, top by confidence:

A	B	Type	Score
PRDX4	CYP27A1	psi-mi:“MI:0915”(physical association)	0.370
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
ATP5F1A	ACOT7	psi-mi:“MI:0914”(association)	0.350
CHCHD10	AKR7A2	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
SPATA20	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): CYP27A1 (Co-fractionation), CYP27A1 (Co-fractionation), CYP27A1 (Co-fractionation), FASN (Co-fractionation), UQCRC2 (Co-fractionation), CYP27A1 (Protein-RNA), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), CYP27A1 (Affinity Capture-MS), PRDX4 (Two-hybrid)

ESM2 similar proteins: A0A087X1C5, B2RXA7, E9Q816, O02766, O15528, O18992, O35084, O35132, O46515, P00191, P03940, P05108, P08686, P0DOX0, P10612, P10635, P12394, P15393, P15539, P15540, P17177, P17178, P70085, P79153, P79202, P97720, Q01361, Q02318, Q16678, Q28827, Q29488, Q2LA59, Q2LA60, Q2LCM1, Q2XNC8, Q2XNC9, Q4G0S4, Q64403, Q64408, Q64429

Diamond homologs: A0A067DE75, A0A067ELB0, A0A098D1J7, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1I9Q5Z0, A0A2Z5U6I9, A0A343URW7, A0A3Q7HBJ5, A0A3Q7HS74, A0A4P8DJC8, A0A6J4BC30, A0AAW1JA93, A0AAW1NEA3, A2Z212, A5BFI4, A9QNE7, C0SJS3, D5JBW9, D5JBX1, E1B2Z9, F6H9N6, H2DH16, I7C6E8, I7CT85, K4CEE8, K4CI52, O18993, O42563, O70537, P05183, P0DO14, P0DOX0, P0DXH8, P17177, P17178, P24557, P30437

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SP3	“up-regulates quantity by expression”	CYP27A1	“transcriptional regulation”
HNF4A	“up-regulates quantity by expression”	CYP27A1	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	CYP27A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1253 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	102
Likely pathogenic	68
Uncertain significance	426
Likely benign	483
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069502	NM_000784.4(CYP27A1):c.1434_1435delinsAA (p.Arg479Ser)	Pathogenic
1071249	NM_000784.4(CYP27A1):c.813C>G (p.Tyr271Ter)	Pathogenic
1076506	NM_000784.4(CYP27A1):c.46dup (p.Ala16fs)	Pathogenic
1385057	NM_000784.4(CYP27A1):c.1333C>T (p.Gln445Ter)	Pathogenic
1385329	NM_000784.4(CYP27A1):c.1087G>T (p.Glu363Ter)	Pathogenic
1393558	NM_000784.4(CYP27A1):c.1191C>A (p.Tyr397Ter)	Pathogenic
1393992	NM_000784.4(CYP27A1):c.253C>T (p.Gln85Ter)	Pathogenic
1418362	NM_000784.4(CYP27A1):c.702del (p.Glu235fs)	Pathogenic
1429007	NM_000784.4(CYP27A1):c.643G>T (p.Glu215Ter)	Pathogenic
1448068	NM_000784.4(CYP27A1):c.426del (p.Thr143fs)	Pathogenic
1455066	NM_000784.4(CYP27A1):c.1339_1342dup (p.Arg448fs)	Pathogenic
1456553	NM_000784.4(CYP27A1):c.1184+1G>C	Pathogenic
1457428	NM_000784.4(CYP27A1):c.765_766del (p.Phe256fs)	Pathogenic
1457639	NM_000784.4(CYP27A1):c.45_46del (p.Ala16fs)	Pathogenic
1457667	NC_000002.11:g.(?219646906)(219647180_?)del	Pathogenic
1458431	NC_000002.11:g.(?219674280)(219679753_?)del	Pathogenic
1460072	NM_000784.4(CYP27A1):c.1435C>A (p.Arg479Ser)	Pathogenic
1804131	NM_000784.4(CYP27A1):c.1297dup (p.Arg433fs)	Pathogenic
1918228	NM_000784.4(CYP27A1):c.1263+1G>T	Pathogenic
1960611	NM_000784.4(CYP27A1):c.667G>T (p.Glu223Ter)	Pathogenic
2006286	NM_000784.4(CYP27A1):c.1140del (p.Phe380fs)	Pathogenic
2009088	NM_000784.4(CYP27A1):c.1375del (p.Arg459fs)	Pathogenic
2023930	NM_000784.4(CYP27A1):c.555del (p.Phe185fs)	Pathogenic
2025240	NC_000002.12:g.218812223dup	Pathogenic
2035798	NM_000784.4(CYP27A1):c.1099_1102dup (p.Val368fs)	Pathogenic
2203263	NM_000784.4(CYP27A1):c.844+1G>T	Pathogenic
2674707	NM_000784.4(CYP27A1):c.303del (p.Pro102fs)	Pathogenic
2674722	NM_000784.4(CYP27A1):c.571C>T (p.Gln191Ter)	Pathogenic
2697865	NM_000784.4(CYP27A1):c.689dup (p.Arg231fs)	Pathogenic
2704216	NM_000784.4(CYP27A1):c.536del (p.Asn179fs)	Pathogenic

SpliceAI

1484 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218809768:G:GG	donor_gain	1.0000
2:218812209:T:A	acceptor_gain	1.0000
2:218812211:C:CA	acceptor_gain	1.0000
2:218812217:T:TA	acceptor_gain	1.0000
2:218812217:TGCA:T	acceptor_loss	1.0000
2:218812218:GCAG:G	acceptor_loss	1.0000
2:218812220:A:AG	acceptor_gain	1.0000
2:218812220:A:T	acceptor_loss	1.0000
2:218812220:AG:A	acceptor_gain	1.0000
2:218812220:AGG:A	acceptor_gain	1.0000
2:218812221:G:GT	acceptor_gain	1.0000
2:218812221:GG:G	acceptor_gain	1.0000
2:218812221:GGG:G	acceptor_gain	1.0000
2:218812221:GGGA:G	acceptor_gain	1.0000
2:218812221:GGGAA:G	acceptor_gain	1.0000
2:218812418:G:GT	donor_gain	1.0000
2:218812418:GAAGG:G	donor_loss	1.0000
2:218812419:A:T	donor_gain	1.0000
2:218812419:AAGGT:A	donor_loss	1.0000
2:218812420:AGGTA:A	donor_loss	1.0000
2:218812422:G:C	donor_loss	1.0000
2:218812423:T:A	donor_loss	1.0000
2:218812910:T:A	acceptor_gain	1.0000
2:218812913:T:TA	acceptor_gain	1.0000
2:218812920:A:AG	acceptor_gain	1.0000
2:218812920:ACAG:A	acceptor_gain	1.0000
2:218812920:ACAGG:A	acceptor_gain	1.0000
2:218812921:C:G	acceptor_gain	1.0000
2:218812921:CAGG:C	acceptor_loss	1.0000
2:218812922:A:AG	acceptor_gain	1.0000

AlphaMissense

3437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218814686:T:C	F469L	0.996
2:218814688:T:A	F469L	0.996
2:218814688:T:G	F469L	0.996
2:218814409:G:C	R405P	0.994
2:218809718:T:A	W133R	0.993
2:218809718:T:C	W133R	0.993
2:218809731:G:C	R137P	0.992
2:218814178:A:T	E392V	0.992
2:218814186:C:A	R395S	0.992
2:218814187:G:C	R395P	0.991
2:218812247:C:A	R158S	0.990
2:218812248:G:C	R158P	0.989
2:218814686:T:A	F469I	0.989
2:218812237:G:C	W154C	0.988
2:218812237:G:T	W154C	0.988
2:218814696:G:A	G472E	0.988
2:218812728:T:A	W275R	0.987
2:218812728:T:C	W275R	0.987
2:218809720:G:C	W133C	0.986
2:218809720:G:T	W133C	0.986
2:218814709:C:G	C476W	0.986
2:218812235:T:A	W154R	0.985
2:218812235:T:C	W154R	0.985
2:218814039:T:A	W346R	0.985
2:218814039:T:C	W346R	0.985
2:218814593:T:C	F438L	0.984
2:218814595:C:A	F438L	0.984
2:218814595:C:G	F438L	0.984
2:218814687:T:G	F469C	0.984
2:218814690:G:A	G470D	0.984

dbSNP variants (sampled 300 via entrez): RS1000084167 (2:218810969 A>C,G), RS1000152962 (2:218781393 T>A,G), RS1000164333 (2:218787949 T>A), RS1000221670 (2:218795114 C>T), RS1000246465 (2:218804314 G>A), RS1000346061 (2:218791386 A>C), RS1000397704 (2:218798128 G>A,T), RS1000412119 (2:218780934 T>C), RS1000472737 (2:218804071 T>A), RS1000510264 (2:218799125 A>C), RS1000530975 (2:218801445 G>A), RS1000583556 (2:218798841 C>T), RS1000788840 (2:218814402 A>G), RS1000835056 (2:218786424 A>G), RS1000860737 (2:218791042 G>T)

Disease associations

OMIM: gene MIM:606530 | disease phenotypes: MIM:213700, MIM:266900

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebrotendinous xanthomatosis	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cerebrotendinous xanthomatosis	Definitive	AR

Mondo (3): cerebrotendinous xanthomatosis (MONDO:0008948), Senior-Loken syndrome 1 (MONDO:0009962), intellectual disability (MONDO:0001071)

Orphanet (3): Cerebrotendinous xanthomatosis (Orphanet:909), Senior-Loken syndrome (Orphanet:3156), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

115 total (30 of 115 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000464	Abnormality of the neck
HP:0000492	Abnormal eyelid morphology
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000708	Atypical behavior
HP:0000713	Agitation
HP:0000716	Depression
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0000762	Decreased nerve conduction velocity
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000991	Xanthomatosis
HP:0001081	Cholelithiasis
HP:0001114	Xanthelasma
HP:0001118	Juvenile cataract
HP:0001138	Optic neuropathy
HP:0001155	Abnormality of the hand
HP:0001167	Abnormal finger morphology

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004611_21	High light scatter reticulocyte count	1.000000e-11
GCST004622_156	Reticulocyte count	1.000000e-12
GCST006630_52	Diastolic blood pressure	7.000000e-18
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST010083_17	Hemoglobin levels	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0006336	diastolic blood pressure
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D019294	Xanthomatosis, Cerebrotendinous	C16.320.565.398.925; C18.452.584.563.925; C18.452.584.750.975; C18.452.648.398.925

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5992 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP24, CYP26 and CYP27 families

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 4d [PMID: 20655626]	Inhibition	7.23	pIC50
CTA091	Inhibition	6.0	pIC50

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.23	IC50	59	nM	CHEMBL1253946
5.36	IC50	4330	nM	CHEMBL363682
5.27	IC50	5340	nM	CHEMBL1253863
5.25	IC50	5690	nM	CHEMBL1253780
5.08	IC50	8230	nM	CHEMBL1253864

PubChem BioAssay actives

5 with measured affinity, of 10 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(2-bromophenyl)methyl]-6-methoxy-3,4-dihydro-2H-naphthalen-1-one	514965: Inhibition of CYP27A1 expressed in CHO cells	ic50	0.0590	uM
(2E)-2-[(2-bromophenyl)methylidene]-6-methoxy-3,4-dihydronaphthalen-1-one	514965: Inhibition of CYP27A1 expressed in CHO cells	ic50	4.3300	uM
6-methoxy-2-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-2H-naphthalen-1-one	514965: Inhibition of CYP27A1 expressed in CHO cells	ic50	5.3400	uM
(2E)-6-methoxy-2-[[2-[(E)-2-phenylethenyl]phenyl]methylidene]-3,4-dihydronaphthalen-1-one	514965: Inhibition of CYP27A1 expressed in CHO cells	ic50	5.6900	uM
2-[(2-ethylphenyl)methyl]-6-methoxy-3,4-dihydro-2H-naphthalen-1-one	514965: Inhibition of CYP27A1 expressed in CHO cells	ic50	8.2300	uM

CTD chemical–gene interactions

87 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
27-hydroxycholesterol	increases chemical synthesis, increases hydroxylation, increases metabolic processing, increases activity, increases oxidation (+2 more)	8
Cholesterol	increases hydroxylation, increases metabolic processing, increases activity, increases reaction, increases chemical synthesis (+4 more)	8
Cyclosporine	affects cotreatment, affects expression, decreases activity, decreases expression, affects abundance	8
3-hydroxy-5-cholestenoic acid	increases metabolic processing, increases oxidation, increases chemical synthesis	4
Acetaminophen	affects cotreatment, decreases expression	4
bisphenol A	increases expression	2
nickel sulfate	decreases expression, increases expression	2
ZM 241385	decreases expression, decreases reaction, increases expression	2
Alitretinoin	decreases expression, increases expression, increases reaction, decreases reaction	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cholic Acids	decreases expression, affects cotreatment, affects expression, affects abundance	2
Dichlorodiphenyl Dichloroethylene	decreases expression, increases expression	2
Methotrexate	decreases expression, decreases reaction, increases expression	2
Valproic Acid	affects expression, decreases expression	2
beta-Naphthoflavone	decreases expression, increases expression	2
4-oxoretinoic acid	decreases expression	1
7-ketocholesterol	increases metabolic processing	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
deoxynivalenol	decreases expression	1
25-hydroxycholesterol	increases metabolic processing, increases chemical synthesis	1
senkirkine	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
hydroxyhydroquinone	increases expression	1
zymosterol	increases metabolic processing	1
linalool	increases expression	1
perfluorooctanoic acid	decreases expression	1
pregna-4,17-diene-3,16-dione	decreases reaction, increases expression	1
beta-hexachlorocyclohexane	increases expression	1
periodate-oxidized adenosine	decreases reaction, increases expression, increases reaction	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1252219	Binding	Inhibition of CYP27A1 expressed in CHO cells	Synthesis and CYP24A1 inhibitory activity of (E)-2-(2-substituted benzylidene)- and 2-(2-substituted benzyl)-6-methoxy-tetralones. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4VG	iPS-CTX-R395S	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

207 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04270682	PHASE3	COMPLETED	Study to Evaluate Patients With Cerebrotendinous Xanthomatosis (RESTORE)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00004346	PHASE2	UNKNOWN	Phase II Study of Cholesterol- and Cholestanol-Free Diet, Lovastatin, and Chenodeoxycholic Acid for Cerebrotendinous Xanthomatosis
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00018694	Not specified	WITHDRAWN	Cholestanol in Humans
NCT00935389	Not specified	COMPLETED	Prospective Study of TW in the Treatment of LN Type V With Gross Proteinuria
NCT01613898	Not specified	UNKNOWN	Evaluation of Carotid IMT and Atherogenic Risk Factors in Patients With Cerebrotendinous Xanthomatosis
NCT02638220	Not specified	COMPLETED	Cerebrotendinous Xanthomatosis (CTX) Prevalence Study
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03584893	Not specified	UNKNOWN	The Prevalence of CTX Disorder in Juvenile Cataract Cases in Turkey
NCT05368038	Not specified	ENROLLING_BY_INVITATION	ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome