Human Gene Module / Chromosome X / OFD1

OFD1OFD1, centriole and centriolar satellite protein

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
7 / 0
EAGLE Score
6
Limited Learn More
Aliases
OFD1, 71-7A,  CXorf5,  JBTS10,  RP23,  SGBS2
Associated Syndromes
Orofaciodigital syndrome I, ASD, DD
Chromosome Band
Xp22.2
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

Molecular Function

This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164. Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis. Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which i

SFARI Genomic Platforms
Reports related to OFD1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Support Genetic landscape of autism spectrum disorder in Vietnamese children Tran KT et al. (2020) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Papuc SM et al. (2023) Yes -
6 Support - Kirsten Furley et al. () No ID
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.935+1G>C - splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.2819T>G p.Leu940Ter stop_gained Unknown - - 38536866 Kirsten Furley et al. ()
c.1066G>C p.Glu356Gln missense_variant Familial - - 28831199 Li J , et al. (2017)
c.260A>G p.Tyr87Cys missense_variant De novo - - 36833254 Papuc SM et al. (2023)
c.1506C>T p.Ser502%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1102-1G>T - splice_site_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.2209A>G p.Thr737Ala missense_variant Familial Maternal Simplex 32193494 Tran KT et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

Score Delta: Score remained at 2

2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
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2

Decreased from 3 to 2

Description

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

4/1/2020
3
icon
3

Decreased from 3 to 3

Description

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

A de novo splice-site variant in the OFD1 gene was identified in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a rare inherited damaging missense variant in OFD1 in a Chinese ASD proband; subsequent Transmission and De Novo Association (TADA) analysis of a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, identified OFD1 as an ASD candidate gene with a PTADA of 0.001754.

Krishnan Probability Score

Score 0.28929768828192

Ranking 25496/25841 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.
ExAC Score

Score 0.98288766184925

Ranking 2047/18225 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
Sanders TADA Score

Score 0.94361098103173

Ranking 15754/18665 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).
Zhang D Score

Score 0.14960130349178

Ranking 5185/20870 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.
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