DDX3XDEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked

SFARI Gene Score

High Confidence, Syndromic Criteria 1.1, Syndromic

Autism Reports / Total Reports

15 / 54

Rare Variants / Common Variants

316 / 0

EAGLE Score

78.6

Strong Learn More

Aliases

DDX3X, CAP-Rf, DBX, DDX14, DDX3, HLP2

Associated Syndromes

Chromosome Band

Xp11.4

Associated Disorders

DD/NDD, ADHD, ID, EP, EPS, ASD

Genetic Category

Rare Single Gene Mutation, Syndromic, Functional

Relevance to Autism

Molecular Function

The protein encoded by this gene is a member of the large DEAD-box protein family, that is defined by the presence of the conserved Asp-Glu-Ala-Asp (DEAD) motif,and acts as a multifunctional ATP-dependent RNA helicase. Nuclear roles for the encoded protein include transcriptional regulation, mRNP assembly, pre-mRNA splicing, and mRNA export, while in the cytoplasm, this protein is thought to be involved in translation and cellular signaling.

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (54)
Variants (316)
Gene Score

Reports related to DDX3X (54 Reports)

#	Type	Title	Author, Year	Autism Report	Associated Disorders
1	Support	The contribution of de novo coding mutations to autism spectrum disorder	Iossifov I et al. (2014)	Yes	-
2	Primary	Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling	Snijders Blok L , et al. (2015)	No	ASD
3	Support	Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern	Fieremans N , et al. (2016)	No	-
4	Support	Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability	Lelieveld SH et al. (2016)	No	-
5	Support	Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder	C Yuen RK et al. (2017)	Yes	-
6	Support	Lessons learned from additional research analyses of unsolved clinical exome cases	Eldomery MK , et al. (2017)	No	Epilepsy/seizures, microcephaly
7	Support	A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology	Vissers LE , et al. (2017)	No	-
8	Support	DDX3X mutations in two girls with a phenotype overlapping Toriello-Carey syndrome	Dikow N , et al. (2017)	No	Hypotonia, microcephaly
9	Support	Genomic diagnosis for children with intellectual disability and/or developmental delay	Bowling KM , et al. (2017)	No	-
10	Support	High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies	Hamdan FF , et al. (2017)	No	DD/ID
11	Support	Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder	Takata A , et al. (2018)	Yes	-
12	Support	A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features	Kellaris G , et al. (2018)	No	-
13	Support	Phenotypic expansion in DDX3X - a common cause of intellectual disability in females	Wang X , et al. (2018)	No	-
14	Support	Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model	Guo H , et al. (2018)	Yes	-
15	Support	Three de novo DDX3X variants associated with distinctive brain developmental abnormalities and brain tumor in intellectually disabled females	Scala M , et al. (2019)	No	Autistic features (hand stereotypies)
16	Support	Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population	Monies D , et al. (2019)	No	Autistic features, stereotypies
17	Support	Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing	Bruel AL , et al. (2019)	No	-
18	Support	Expansion of phenotype of DDX3X syndrome: six new cases	Beal B , et al. (2019)	No	-
19	Support	Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks	Ruzzo EK , et al. (2019)	Yes	-
20	Recent Recommendation	Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development	Lennox AL et al. (2020)	No	ASD, ADHD
21	Support	Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability	Chevarin M et al. (2020)	No	Marfanoid habitus
22	Support	-	Hildebrand MS et al. (2020)	No	ASD, DD, ID
23	Support	A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders	Suzuki T et al. (2020)	No	-
24	Support	A de novo DDX3X Variant Is Associated With Syndromic Intellectual Disability: Case Report and Literature Review	Chen Y et al. (2020)	No	DD, ID, epilepsy/seizures, stereotypy
25	Support	Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders	Wang T et al. (2020)	Yes	-
26	Support	-	Ohashi K et al. (2021)	Yes	-
27	Support	-	Brunet T et al. (2021)	No	ASD, ID
28	Support	-	Tang L et al. (2021)	No	ASD, DD
29	Support	-	Boitnott A et al. (2021)	No	-
30	Support	-	Valentino F et al. (2021)	Yes	DD
31	Support	-	Pode-Shakked B et al. (2021)	No	-
32	Support	-	Mahjani B et al. (2021)	Yes	-
33	Support	-	Bruno LP et al. (2021)	Yes	-
34	Support	-	ÃÂlvarez-Mora MI et al. (2022)	No	-
35	Support	-	Stefaniak U et al. (2022)	Yes	-
36	Support	-	Leite AJDC et al. (2022)	No	-
37	Support	-	Dai Y et al. (2022)	No	ASD, epilepsy/seizures
38	Support	-	Shen H et al. (2022)	No	-
39	Support	-	Hu C et al. (2022)	Yes	-
40	Support	-	Hoye ML et al. (2022)	No	-
41	Support	-	Levchenko O et al. (2022)	No	-
42	Support	-	Zhou X et al. (2022)	Yes	-
43	Recent Recommendation	-	Kundishora AJ et al. (2023)	No	ASD, DD
44	Support	-	Chaves LD et al. (2023)	No	DD
45	Support	-	Miyake N et al. (2023)	Yes	-
46	Support	-	Spataro N et al. (2023)	No	-
47	Support	-	Hu C et al. (2023)	Yes	-
48	Support	-	Kipkemoi P et al. (2023)	No	ASD, epilepsy/seizures, stereotypy
49	Support	-	Amerh S Alqahtani et al. (2023)	No	-
50	Recent Recommendation	-	Alejandro Parra et al. (2024)	No	ASD, ADHD
51	Support	-	M Cecilia Poli et al. ()	No	-
52	Support	-	Magdalena Badura-Stronka et al. (2024)	No	DD, stereotypy
53	Support	-	Tamam Khalaf et al. (2024)	No	ASD, ADHD, epilepsy/seizures
54	Support	-	Axel Schmidt et al. (2024)	No	ID

Rare Variants (316)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	stop_gained	De novo	-	-	30349862	Wang X , et al. (2018)
-	-	inframe_deletion	De novo	-	-	30349862	Wang X , et al. (2018)
-	-	inframe_deletion	De novo	-	-	30936465	Scala M , et al. (2019)
-	-	frameshift_variant	De novo	-	-	30349862	Wang X , et al. (2018)
-	-	frameshift_variant	De novo	-	-	31274575	Beal B , et al. (2019)
-	-	splice_region_variant	De novo	-	-	30349862	Wang X , et al. (2018)
-	-	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.-82G>A	-	splice_site_variant	De novo	-	-	30349862	Wang X , et al. (2018)
-	-	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
-	-	splice_site_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.600T>A	p.Tyr200Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.889C>T	p.Pro297Ser	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.1498-2A>G	-	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1770-1G>A	-	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.284+1G>A	-	splice_site_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.-82G>A	-	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.-82G>C	-	splice_site_variant	Unknown	-	-	32135084	Lennox AL et al. (2020)
c.1712T>A	p.Leu571Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.1029C>A	p.Tyr343Ter	stop_gained	De novo	-	-	35982159	Zhou X et al. (2022)
c.874C>T	p.Arg292Ter	stop_gained	De novo	-	-	30349862	Wang X , et al. (2018)
c.71C>A	p.Ser24Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.79C>T	p.Gln27Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.46-2A>G	-	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
-	-	frameshift_variant	De novo	-	Simplex	28327206	Eldomery MK , et al. (2017)
c.103+15T>C	-	intron_variant	Familial	Maternal	-	37007974	Hu C et al. (2023)
c.1386C>G	p.Tyr462Ter	stop_gained	Unknown	-	-	30349862	Wang X , et al. (2018)
c.173C>A	p.Ser58Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.233C>G	p.Ser78Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.151+1G>T	-	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.284+1G>A	-	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1615+14T>C	-	intron_variant	Familial	Maternal	-	37007974	Hu C et al. (2023)
c.26C>G	p.Ala9Gly	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.599dup	p.Tyr200Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.619C>T	p.Gln207Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.731C>G	p.Ser244Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.745G>T	p.Glu249Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.874C>T	p.Arg292Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1171-2A>G	-	splice_site_variant	Unknown	-	-	36943625	Chaves LD et al. (2023)
c.88G>C	p.Gly30Arg	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1372G>T	p.Glu458Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1710G>A	p.Trp570Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1728T>G	p.Tyr576Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1804C>T	p.Arg602Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1807C>T	p.Arg603Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.233C>G	p.Ser78Ter	stop_gained	De novo	-	-	28333917	Vissers LE , et al. (2017)
c.71C>A	p.Ser24Ter	stop_gained	Unknown	-	-	38438125	Tamam Khalaf et al. (2024)
c.136C>T	p.Arg46Ter	stop_gained	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.865-1G>A	-	splice_site_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.703C>T	p.Leu235%3D	missense_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.895G>A	p.Val299Met	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.898G>T	p.Val300Phe	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.971C>A	p.Pro324Gln	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.976C>T	p.Arg326Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.641T>C	p.Ile214Thr	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.46-2A>G	-	splice_site_variant	De novo	-	Simplex	30564305	Guo H , et al. (2018)
c.-73_-72insTATA	-	frameshift_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1641insT	p.Arg548Ter	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.619C>T	p.Gln207Ter	stop_gained	De novo	-	-	28554332	Bowling KM , et al. (2017)
c.745G>T	p.Glu249Ter	stop_gained	De novo	-	-	28554332	Bowling KM , et al. (2017)
c.865-2A>G	-	splice_site_variant	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.894C>A	p.Cys298Ter	stop_gained	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1171-2A>C	-	splice_site_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1126C>T	p.Arg376Cys	missense_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.1595C>T	p.Thr532Met	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1666T>G	p.Leu556Val	missense_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.1703C>T	p.Pro568Leu	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.865-1G>C	-	splice_site_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.758C>T	p.Ala253Val	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.887G>C	p.Arg296Pro	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.949T>C	p.Cys317Arg	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.577G>T	p.Gly193Ter	stop_gained	De novo	-	-	27159028	Fieremans N , et al. (2016)
c.780T>G	p.Tyr260Ter	stop_gained	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.1316-2A>G	-	splice_site_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.-78del	-	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1628C>G	p.Ser543Ter	stop_gained	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.544-8_544-6del	-	splice_region_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.922C>T	p.Gln308Ter	stop_gained	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.1498-2A>G	-	splice_site_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.1021T>C	p.Cys341Arg	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1244T>A	p.Ile415Asn	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1304T>C	p.Leu435Pro	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1438A>G	p.Arg480Gly	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1595C>T	p.Thr532Met	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1600C>T	p.Arg534Cys	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.1805G>A	p.Arg602Gln	missense_variant	De novo	-	-	30349862	Wang X , et al. (2018)
c.119C>G	p.Pro40Arg	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.281G>A	p.Gly94Glu	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.113A>G	p.Tyr38Cys	missense_variant	De novo	-	-	36943625	Chaves LD et al. (2023)
c.43C>T	p.Gln15Ter	stop_gained	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.-83A>G	-	splice_site_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1710G>A	p.Trp570Ter	stop_gained	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.1600C>G	p.Arg534Gly	missense_variant	De novo	-	-	28371085	Dikow N , et al. (2017)
c.1703C>T	p.Pro568Leu	missense_variant	De novo	-	-	28371085	Dikow N , et al. (2017)
c.1511G>A	p.Gly504Glu	missense_variant	De novo	-	-	30936465	Scala M , et al. (2019)
c.1502C>A	p.Ala501Glu	missense_variant	De novo	-	-	33590427	Ohashi K et al. (2021)
c.544T>G	p.Phe182Val	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.569T>G	p.Ile190Ser	missense_variant	Unknown	-	-	32135084	Lennox AL et al. (2020)
c.592A>C	p.Thr198Pro	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.610A>C	p.Thr204Pro	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.616G>A	p.Val206Met	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.672C>T	p.Ala224%3D	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.698C>T	p.Ala233Val	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.704T>A	p.Leu235Gln	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.764A>G	p.Lys255Arg	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.857C>A	p.Ala286Asp	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.878C>T	p.Ser293Phe	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.887G>C	p.Arg296Pro	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.968C>T	p.Thr323Ile	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.977G>A	p.Arg326His	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.136C>T	p.Arg46Ter	stop_gained	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.443+1G>C	-	splice_site_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.865-1G>C	-	splice_site_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.46-2A>G	-	splice_site_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1766A>G	p.Lys589Arg	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.262_264del	p.Arg88del	inframe_deletion	De novo	-	-	30349862	Wang X , et al. (2018)
c.1616-2A>G	-	splice_site_variant	De novo	-	Simplex	32530565	Suzuki T et al. (2020)
c.1088G>A	p.Arg363Lys	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1126C>T	p.Arg376Cys	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1175T>C	p.Leu392Pro	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1243A>T	p.Ile415Phe	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1250A>C	p.Gln417Pro	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1292T>G	p.Leu431Arg	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1438A>G	p.Arg480Gly	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1439G>C	p.Arg480Thr	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1462C>T	p.Arg488Cys	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1463G>A	p.Arg488His	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1481T>G	p.Ile494Ser	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1490C>T	p.Ala497Val	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1493C>T	p.Thr498Ile	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1513C>G	p.Leu505Val	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1541T>C	p.Ile514Thr	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1582C>T	p.Arg528Cys	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1595C>T	p.Thr532Met	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1676T>A	p.Leu559His	missense_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1177G>A	p.Ala393Thr	missense_variant	Unknown	-	-	34615535	Mahjani B et al. (2021)
c.70T>A	p.Ser24Thr	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.75T>G	p.Asp25Glu	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.584T>G	p.Ile195Ser	missense_variant	De novo	-	-	35390071	Leite AJDC et al. (2022)
c.489C>G	p.Tyr163Ter	stop_gained	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.874C>T	p.Arg292Ter	stop_gained	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.136C>T	p.Arg46Ter	stop_gained	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.233C>G	p.Ser78Ter	stop_gained	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.70T>G	p.Ser24Ala	missense_variant	Familial	Maternal	-	35741772	Hu C et al. (2022)
c.1045G>A	p.Ala349Thr	missense_variant	De novo	-	-	38177409	M Cecilia Poli et al. ()
c.976C>T	p.Arg326Cys	missense_variant	De novo	-	-	34356170	Valentino F et al. (2021)
c.1325C>G	p.Ser442Ter	stop_gained	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.873C>A	p.Tyr291Ter	stop_gained	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.931C>T	p.Arg311Ter	stop_gained	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.605G>C	p.Arg202Pro	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.611C>T	p.Thr204Ile	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.635C>T	p.Pro212Leu	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1846_1848del	p.Ser616del	inframe_deletion	De novo	-	-	35982159	Zhou X et al. (2022)
c.551A>G	p.Asp184Gly	splice_site_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.894C>A	p.Cys298Ter	stop_gained	De novo	-	Simplex	37463579	Kipkemoi P et al. (2023)
c.1171-2A>G	-	splice_site_variant	De novo	-	Simplex	25363768	Iossifov I et al. (2014)
c.766-8_766-2del	-	splice_site_variant	Unknown	-	-	38438125	Tamam Khalaf et al. (2024)
c.1693C>T	p.Gln565Ter	stop_gained	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1051C>T	p.Arg351Trp	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1084C>G	p.Arg362Gly	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1463G>A	p.Arg488His	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1595C>T	p.Thr532Met	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1679T>G	p.Leu560Arg	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1703C>T	p.Pro568Leu	missense_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.3G>A	p.Met1?	initiator_codon_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.875G>T	p.Arg292Leu	missense_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.976C>T	p.Arg326Cys	missense_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.1529T>C	p.Val510Ala	missense_variant	Unknown	-	-	38438125	Tamam Khalaf et al. (2024)
c.1487T>G	p.Val496Gly	missense_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.329G>A	p.Arg110His	missense_variant	Familial	Maternal	-	35392274	Dai Y et al. (2022)
c.869dup	p.Tyr291IlefsTer4	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1091T>C	p.Ile364Thr	missense_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
c.3G>C	p.Met1?	initiator_codon_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.724dup	p.Ile242AsnfsTer53	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1868dup	p.Gly624ArgfsTer6	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.679+3_679+4inv	-	splice_region_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.107G>A	p.Gly36Glu	missense_variant	Familial	Maternal	-	30349862	Wang X , et al. (2018)
c.226dup	p.Ser76LysfsTer2	splice_site_variant	De novo	-	-	31274575	Beal B , et al. (2019)
c.977G>A	p.Arg326His	missense_variant	De novo	-	Unknown	33619735	Brunet T et al. (2021)
c.1138_1140del	p.Met380del	inframe_deletion	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1206_1208del	p.Phe402del	inframe_deletion	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1244_1246del	p.Ile415del	inframe_deletion	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1491_1493del	p.Thr498del	inframe_deletion	De novo	-	-	32135084	Lennox AL et al. (2020)
c.693_695del	p.Ala233del	inframe_deletion	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1834dup	p.Ser612LysfsTer19	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1745dup	p.Ser583Ter	frameshift_variant	De novo	-	Simplex	32714884	Chen Y et al. (2020)
c.1513C>G	p.Leu505Val	missense_variant	De novo	-	Multiplex	35982159	Zhou X et al. (2022)
c.1148C>G	p.Ala383Gly	missense_variant	De novo	-	Unknown	33619735	Brunet T et al. (2021)
c.1502C>A	p.Ala501Glu	missense_variant	De novo	-	Simplex	36973392	Miyake N et al. (2023)
c.80dup	p.Ser28GlufsTer23	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.192dup	p.Asp65ArgfsTer2	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.977G>A	p.Arg326His	missense_variant	De novo	-	Simplex	29346770	Takata A , et al. (2018)
c.841C>T	p.Gln281Ter	stop_gained	De novo	-	Multiplex	39039281	Axel Schmidt et al. (2024)
c.1126C>T	p.Arg376Cys	missense_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.1415A>G	p.His472Arg	missense_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.1541T>C	p.Ile514Thr	missense_variant	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.1583G>A	p.Arg528His	missense_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.1594A>G	p.Thr532Ala	missense_variant	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.581A>T	p.Asn194Ile	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.641T>C	p.Ile214Thr	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.698C>T	p.Ala233Val	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.704T>C	p.Leu235Pro	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.977G>A	p.Arg326His	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.236_241dup	p.Arg79_Gly80dup	inframe_insertion	De novo	-	-	30349862	Wang X , et al. (2018)
c.1144A>C	p.Ser382Arg	missense_variant	De novo	-	Simplex	32135084	Lennox AL et al. (2020)
c.1245C>G	p.Ile415Met	missense_variant	De novo	-	Simplex	32135084	Lennox AL et al. (2020)
c.599A>G	p.Tyr200Cys	missense_variant	De novo	-	Simplex	37463579	Kipkemoi P et al. (2023)
c.113A>G	p.Tyr38Cys	missense_variant	De novo	-	Simplex	35887114	Levchenko O et al. (2022)
c.1497+1G>C	-	splice_site_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1126C>T	p.Arg376Cys	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1175T>C	p.Leu392Pro	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1250A>C	p.Gln417Pro	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1423C>G	p.Arg475Gly	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1440A>T	p.Arg480Ser	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1463G>A	p.Arg488His	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1520T>C	p.Ile507Thr	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1541T>C	p.Ile514Thr	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1601G>A	p.Arg534His	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1703C>T	p.Pro568Leu	missense_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1678_1680del	p.Leu560del	inframe_deletion	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.853G>A	p.Glu285Lys	missense_variant	Unknown	Not maternal	-	33993884	Tang L et al. (2021)
NM_001193416.1:c.1804C>T	p.Arg602Ter	stop_gained	De novo	-	-	30349862	Wang X , et al. (2018)
c.147del	p.Gly51ValfsTer170	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.623del	p.Lys208SerfsTer13	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.691dup	p.Thr231AsnfsTer64	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.868del	p.Ser290HisfsTer31	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1321del	p.Asp441IlefsTer3	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1383dup	p.Tyr462IlefsTer3	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1462del	p.Arg488AlafsTer8	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1601G>A	p.Arg534His	missense_variant	De novo	-	Simplex	29100083	Hamdan FF , et al. (2017)
c.1582C>T	p.Arg528Cys	missense_variant	De novo	-	Simplex	37463579	Kipkemoi P et al. (2023)
c.1072G>T	p.Glu358Ter	stop_gained	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1382T>A	p.Leu461Ter	stop_gained	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.599dup	p.Tyr200Ter	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1138_1140del	p.Met380del	inframe_deletion	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.1206_1208del	p.Phe402del	inframe_deletion	De novo	-	Simplex	33993884	Tang L et al. (2021)
-	-	frameshift_variant	De novo	-	Multiplex (monozygotic twins)	30349862	Wang X , et al. (2018)
c.241_242insCTT	p.Lys81delinsThrTer	stop_gained	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1052G>A	p.Arg351Gln	missense_variant	Familial	Maternal	-	32135084	Lennox AL et al. (2020)
c.1105A>G	p.Thr369Ala	missense_variant	Familial	Maternal	-	32135084	Lennox AL et al. (2020)
c.1399G>T	p.Ala467Ser	missense_variant	Familial	Maternal	-	32135084	Lennox AL et al. (2020)
c.147del	p.Gly51ValfsTer170	frameshift_variant	Familial	-	-	31231135	Bruel AL , et al. (2019)
c.833dup	p.Leu278PhefsTer17	frameshift_variant	Familial	-	-	31231135	Bruel AL , et al. (2019)
c.1105dup	p.Thr369AsnfsTer14	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1256del	p.Val419GlufsTer17	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1099dup	p.Gln367ProfsTer16	frameshift_variant	De novo	-	-	36980980	Spataro N et al. (2023)
c.45+12G>A	-	intron_variant	Unknown	Not maternal	Simplex	35326346	Stefaniak U et al. (2022)
c.269dup	p.Ser90ArgfsTer8	frameshift_variant	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.758C>T	p.Ala253Val	missense_variant	De novo	-	Simplex	28327206	Eldomery MK , et al. (2017)
c.426_437del	p.Ser143_Leu146del	frameshift_variant	De novo	-	-	31274575	Beal B , et al. (2019)
c.685_687del	p.Gly229del	inframe_deletion	Unknown	-	Simplex	31130284	Monies D , et al. (2019)
c.734_736del	p.Asp245del	inframe_deletion	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.371del	p.Asn124ThrfsTer97	frameshift_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1579del	p.His527IlefsTer9	frameshift_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1776dup	p.Ser593Ter	frameshift_variant	De novo	-	Multiplex	31398340	Ruzzo EK , et al. (2019)
c.362G>T	p.Arg121Leu	missense_variant	Familial	Maternal	-	28327206	Eldomery MK , et al. (2017)
c.26C>T	p.Ala9Val	missense_variant	Familial	Maternal	-	37904618	Alejandro Parra et al. (2024)
c.1257_1259del	p.Val420del	inframe_deletion	Unknown	-	-	37904618	Alejandro Parra et al. (2024)
c.1633insT	p.Phe545PhefsTer2	frameshift_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.126_129del	p.His42GlnfsTer178	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.830_831del	p.Glu277ValfsTer17	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.831_832dup	p.Leu278CysfsTer44	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1746del	p.Ser583AlafsTer86	frameshift_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1628C>T	p.Ser543Leu	missense_variant	De novo	-	Simplex	34580403	Pode-Shakked B et al. (2021)
c.572T>A	p.Ile191Asn	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.710C>T	p.Pro237Leu	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.744C>T	p.Gly248=	synonymous_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.251G>T	p.Gly84Val	missense_variant	Familial	Maternal	Simplex	34948243	Bruno LP et al. (2021)
c.1276_1279del	p.Asp426AsnfsTer9	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1534_1535del	p.His512CysfsTer5	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1535_1536del	p.His512ArgfsTer5	frameshift_variant	Unknown	-	-	32135084	Lennox AL et al. (2020)
c.1022G>A	p.Cys341Tyr	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1199A>G	p.Tyr400Cys	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1208T>G	p.Leu403Trp	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1213G>T	p.Val405Leu	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1279A>C	p.Lys427Gln	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1600C>T	p.Arg534Cys	missense_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.160dup	p.Asp54GlyfsTer2	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1199_1200delinsC	p.Tyr400SerfsTer6	frameshift_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1395_1399del	p.Tyr466MetfsTer13	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.641del	p.Ile214ThrfsTer7	frameshift_variant	De novo	-	Simplex	28263302	C Yuen RK et al. (2017)
c.856G>A	p.Ala286Thr	missense_variant	Unknown	Not maternal	-	27159028	Fieremans N , et al. (2016)
c.697G>A	p.Ala233Thr	missense_variant	Familial	Maternal	-	37904618	Alejandro Parra et al. (2024)
c.1230dup	p.Thr411TyrfsTer3	frameshift_variant	De novo	-	-	37904618	Alejandro Parra et al. (2024)
c.620_626dup	p.His209GlnfsTer88	frameshift_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.749_756del	p.Ala250GlyfsTer42	frameshift_variant	De novo	-	Simplex	35392274	Dai Y et al. (2022)
c.1052G>A	p.Arg351Gln	missense_variant	Familial	Maternal	-	37904618	Alejandro Parra et al. (2024)
c.655dup	p.Asp219GlyfsTer76	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1321del	p.Asp441IlefsTer3	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1383dup	p.Tyr462IlefsTer3	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.723_724del	p.Gln241HisfsTer53	frameshift_variant	De novo	-	Simplex	33993884	Tang L et al. (2021)
c.641_643delinsCC	p.Ile214ThrfsTer7	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.749_750insGCCTC	p.Leu251ProfsTer3	frameshift_variant	De novo	-	-	32135084	Lennox AL et al. (2020)
c.147del	p.Gly51ValfsTer170	frameshift_variant	De novo	-	Simplex	32277047	Chevarin M et al. (2020)
c.641_643del	p.Ile214del	inframe_deletion	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1415A>G	p.His472Arg	missense_variant	De novo	-	Simplex	35183220	ÃÂlvarez-Mora MI et al. (2022)
c.1229_1230dup	p.Thr411LeufsTer10	frameshift_variant	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.1395_1399del	p.Tyr466MetfsTer13	frameshift_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.236G>A	p.Arg79Lys	missense_variant	Familial	Maternal	Multiplex	29490693	Kellaris G , et al. (2018)
c.1474del	p.Ser492AlafsTer4	frameshift_variant	De novo	-	Simplex	32345733	Hildebrand MS et al. (2020)
c.439_440dup	p.Gln148AsnfsTer74	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.590_591del	p.Leu197HisfsTer97	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.1535_1536del	p.His512ArgfsTer5	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.830_831del	p.Glu277ValfsTer17	frameshift_variant	Unknown	-	-	37799141	Amerh S Alqahtani et al. (2023)
c.1371_1382delinsCTC	p.Glu458_Leu461delinsSer	inframe_indel	De novo	-	-	32135084	Lennox AL et al. (2020)
c.1384_1385dup	p.His463ThrfsTer34	frameshift_variant	De novo	-	Simplex	32135084	Lennox AL et al. (2020)
c.893dup	p.Cys298TrpfsTer51	frameshift_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1229_1230dup	p.Thr411LeufsTer10	frameshift_variant	De novo	-	-	26235985	Snijders Blok L , et al. (2015)
c.491_494delinsTCTC	p.Asp164_Asp165delinsValSer	inframe_indel	De novo	-	-	30936465	Scala M , et al. (2019)
c.123_124del	p.His42PhefsTer8	frameshift_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.898G>T	p.Val300Phe	missense_variant	Familial	Maternal	Multiplex	26235985	Snijders Blok L , et al. (2015)
c.644_645del	p.Lys215ArgfsTer79	frameshift_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.1535_1536del	p.His512ArgfsTer5	frameshift_variant	De novo	-	Simplex	37904618	Alejandro Parra et al. (2024)
c.595A>C;c.643A>C	p.Lys199Gln;p.Lys215Gln	missense_variant	De novo	-	Simplex	28263302	C Yuen RK et al. (2017)
c.107G>A	p.Gly36Glu	missense_variant	Familial	Maternal	Extended multiplex	26235985	Snijders Blok L , et al. (2015)
c.1084C>T	p.Arg362Cys	missense_variant	Familial	Maternal	Extended multiplex	26235985	Snijders Blok L , et al. (2015)
c.1658_1661del	p.Thr553ArgfsTer18	frameshift_variant	De novo	-	Simplex	38328757	Magdalena Badura-Stronka et al. (2024)

Common Variants

No common variants reported.

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

See SFARI Gene'scoring criteria

High Confidence

See all Category 1 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.

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."

4/1/2021

Score remained at 1

Description

35 unique de novo variants (including 19 predicted loss-of-function alleles and 5 missense variants experimentally shown to be loss-of-function) in the DDX3X gene were identified in 38 female cases with intellectual disability, 20 of whom also presented with behavioral problems including autism spectrum disorder, hyperactivity, and aggression (Snijders Blok et al., 2015). A de novo splice-site variant in this gene was also identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo loss-of-function variant in the DDX3X gene was identified in an ASD proband from a simplex family from the ASD: Genomes to Outcome Study cohort by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of two de novo LoF variants in this gene, a probability of LoF intolerance rate (pLI) > 0.9, and higher-than-expected mutation rate (false discovery rate < 15%), DDX3X was classified as an ASD candidate gene in Yuen et al., 2017.

Reports Added

[Prospective and detailed behavioral phenotyping in DDX3X syndrome2021]

1/1/2021

Score remained at 1

Description

Reports Added

[Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings2021] [De novo variants in neurodevelopmental disorders-experiences from a tertiary care center2021]

10/1/2020

Score remained at 1

Description

Reports Added

[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]

7/1/2020

Score remained at 1

Description

Reports Added

[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020] [A de novo DDX3X Variant Is Associated With Syndromic Intellectual Disability: Case Report and Literature Review2020]

4/1/2020

Score remained at 1

Description

Reports Added

[Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development2020] [Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020]

10/1/2019

Decreased from 2S to 1

New Scoring Scheme

Description

Reports Added

[New Scoring Scheme]

7/1/2019

Decreased from 2S to 2S

Description

Reports Added

[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.2019] [Expansion of phenotype of DDX3X syndrome: six new cases.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]

4/1/2019

Decreased from 2S to 2S

Description

Reports Added

[Three de novo DDX3X variants associated with distinctive brain developmental abnormalities and brain tumor in intellectually disabled females.2019]

1/1/2019

Decreased from 2S to 2S

Description

Reports Added

[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]

10/1/2018

Decreased from 2S to 2S

Description

Reports Added

[Phenotypic expansion in DDX3X - a common cause of intellectual disability in females.2018]

10/1/2017

Decreased from 2S to 2S

Description

Reports Added

[High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.2017]

4/1/2017

Decreased from 3S to 2S

Description

Reports Added

[Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Identification of Intellectual Disability Genes in Female Patients with A Skewed X Inactivation Pattern.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Lessons learned from additional research analyses of unsolved clinical exome cases.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [DDX3X mutations in two girls with a phenotype overlapping Toriello-Carey syndrome.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]

7/1/2016

Decreased from 3S to 3S

Description

Reports Added

[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]

4/1/2016

Decreased from 3S to 3S

Description

Reports Added

7/1/2015

Increased from to 3S

Description

Krishnan Probability Score

Score 0.5862682256489

Ranking 514/25841 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 0.99893006535012

Ranking 1082/18225 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 0.47427199943605

Ranking 396/18665 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 0.29074388690476

Ranking 2871/20870 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

Human Gene Module / Chromosome X / DDX3X

DDX3XDEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

EAGLE Score

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Genetic Category

Relevance to Autism

Molecular Function

External Links

Human

Mouse

SFARI Genomic Platforms

Reports related to DDX3X (54 Reports)

Rare Variants (316)

Common Variants

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

High Confidence

Syndromic

4/1/2021

Score remained at 1

Description

Reports Added

1/1/2021

Score remained at 1

Description

Reports Added

10/1/2020

Score remained at 1

Description

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7/1/2020

Score remained at 1

Description

Reports Added

4/1/2020

Score remained at 1

Description

Reports Added

10/1/2019

Decreased from 2S to 1

New Scoring Scheme

Description

Reports Added

7/1/2019

Decreased from 2S to 2S

Description

Reports Added

4/1/2019

Decreased from 2S to 2S

Description

Reports Added

1/1/2019

Decreased from 2S to 2S

Description

Reports Added

10/1/2018

Decreased from 2S to 2S

Description

Reports Added

10/1/2017

Decreased from 2S to 2S

Description

Reports Added

4/1/2017

Decreased from 3S to 2S

Description

Reports Added

7/1/2016

Decreased from 3S to 3S

Description

Reports Added

4/1/2016