Human Gene Module / Chromosome 2 / CYP27A1

CYP27A1cytochrome P450 family 27 subfamily A member 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
13 / 0
Aliases
CYP27A1, CP27,  CTX,  CYP27
Associated Syndromes
-
Chromosome Band
2q35
Associated Disorders
ASD
Relevance to Autism

Homozygous or compound heterozygous variants in the CYP27A1 gene are responsible for cerebrotendinous xanthomatosis (CTX; OMIM 213700), a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts (Gallus et al., 2006). Review of a retrospective patient file of 77 genetically confirmed Dutch CTS patients determined that 10 patients (13%; nine pediatric and one adult) had a diagnosis of ASD (Stelten et al., 2017); the authors suggested that ASD was a possibly underestimated frequent feature in CTX patients.

Molecular Function

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to CYP27A1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene Gallus GN , et al. (2006) No -
2 Primary Autism spectrum disorder: an early and frequent feature in cerebrotendinous xanthomatosis Stelten BML , et al. (2017) No ASD
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support Patients with Lately Diagnosed Cerebrotendinous Xanthomatosis Yunisova G et al. (2019) No ASD
5 Support - Zou D et al. (2021) No -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Suhua Chang et al. () Yes -
Rare Variants   (13)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.63C>T p.Cys21= synonymous_variant De novo - Simplex 39126614 Suhua Chang et al. ()
c.510A>C p.Glu170Asp missense_variant Familial Maternal - 34145886 Zou D et al. (2021)
c.1415G>C p.Gly472Ala missense_variant Familial Paternal - 34145886 Zou D et al. (2021)
c.968G>A p.Arg323Gln missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1263+1G>A - splice_site_variant Familial - Simplex 28894950 Stelten BML , et al. (2017)
c.850A>T p.Lys284Ter stop_gained Familial - Multiplex 28894950 Stelten BML , et al. (2017)
c.1184+1G>A - splice_site_variant Familial - Multiplex 28894950 Stelten BML , et al. (2017)
c.1421G>A p.Arg474Gln missense_variant Familial - Simplex 28894950 Stelten BML , et al. (2017)
c.475C>T p.Gln159Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.646G>A p.Ala216Thr missense_variant Familial - Multiplex 28894950 Stelten BML , et al. (2017)
c.1016C>T p.Thr339Met missense_variant Familial - Multiplex 28894950 Stelten BML , et al. (2017)
c.1183C>T p.Arg395Cys missense_variant Familial - Multiplex 28894950 Stelten BML , et al. (2017)
c.1016C>T p.Thr339Met missense_variant Familial Both parents Simplex 28894950 Stelten BML , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Homozygous or compound heterozygous variants in the CYP27A1 gene are responsible for cerebrotendinous xanthomatosis (CTX; OMIM 213700), a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts (Gallus et al., 2006). Review of a retrospective patient file of 77 genetically confirmed Dutch CTS patients determined that 10 patients (13%; nine pediatric and one adult) had a diagnosis of ASD (Stelten et al., 2017); the authors suggested that ASD was a possibly underestimated frequent feature in CTX patients.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2020
S
icon
S

Score remained at S

Description

Homozygous or compound heterozygous variants in the CYP27A1 gene are responsible for cerebrotendinous xanthomatosis (CTX; OMIM 213700), a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts (Gallus et al., 2006). Review of a retrospective patient file of 77 genetically confirmed Dutch CTS patients determined that 10 patients (13%; nine pediatric and one adult) had a diagnosis of ASD (Stelten et al., 2017); the authors suggested that ASD was a possibly underestimated frequent feature in CTX patients.

Reports Added
[Patients with Lately Diagnosed Cerebrotendinous Xanthomatosis2019]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Homozygous or compound heterozygous variants in the CYP27A1 gene are responsible for cerebrotendinous xanthomatosis (CTX; OMIM 213700), a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts (Gallus et al., 2006). Review of a retrospective patient file of 77 genetically confirmed Dutch CTS patients determined that 10 patients (13%; nine pediatric and one adult) had a diagnosis of ASD (Stelten et al., 2017); the authors suggested that ASD was a possibly underestimated frequent feature in CTX patients.

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Homozygous or compound heterozygous variants in the CYP27A1 gene are responsible for cerebrotendinous xanthomatosis (CTX; OMIM 213700), a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts (Gallus et al., 2006). Review of a retrospective patient file of 77 genetically confirmed Dutch CTS patients determined that 10 patients (13%; nine pediatric and one adult) had a diagnosis of ASD (Stelten et al., 2017); the authors suggested that ASD was a possibly underestimated frequent feature in CTX patients.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
Krishnan Probability Score

Score 0.41237085126559

Ranking 22122/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 3.8968187506163E-11

Ranking 17039/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.77241037125645

Ranking 1803/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.39170204298787

Ranking 18279/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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