DDX6

DEAD-box helicase 6, the group of DEAD-box helicases

Basic information

Region (hg38): 11:118747763-118791164

Previous symbols: [ "HLR2" ]

Links

ENSG00000110367 ∙ NCBI:1656 ∙ OMIM:600326 ∙ HGNC:2747 ∙ Uniprot:P26196 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder with impaired language and dysmorphic facies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with impaired language and dysmorphic facies	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	31422817

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDX6 gene.

• not provided (1 variants)
• Intellectual developmental disorder with impaired language and dysmorphic facies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDX6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense	1	2	22	2		27
nonsense			3			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				4	1	5
non coding			2		3	5
Total	1	2	28	4	4

Variants in DDX6

This is a list of pathogenic ClinVar variants found in the DDX6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-118752035-G-A			Benign (Sep 14, 2021)
11-118752276-T-C			Benign (Sep 14, 2021)
11-118754716-G-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
11-118754768-T-C			Uncertain significance (Oct 18, 2023)
11-118754770-T-A		Intellectual developmental disorder with impaired language and dysmorphic facies	Uncertain significance (Jun 24, 2022)
11-118754809-T-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
11-118754828-G-C		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
11-118754879-C-T			Uncertain significance (Jul 08, 2022)
11-118754900-C-T		Intellectual developmental disorder with impaired language and dysmorphic facies	Benign (Jul 30, 2021)
11-118755447-A-G		Intellectual developmental disorder with impaired language and dysmorphic facies	Uncertain significance (Mar 29, 2024)
11-118755477-G-C			Uncertain significance (Jun 30, 2022)
11-118755491-C-T		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic/Likely pathogenic (Jun 06, 2022)
11-118755492-G-A		not specified	Uncertain significance (Oct 26, 2023)
11-118755506-T-TA		DDX6-related disorder	Likely benign (Apr 29, 2020)
11-118756262-G-A		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic (Aug 29, 2022)
11-118756263-T-G		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic (Nov 08, 2019)
11-118756266-A-G		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic (Nov 08, 2019)
11-118756278-G-A		Intellectual developmental disorder with impaired language and dysmorphic facies	Conflicting classifications of pathogenicity (Nov 01, 2023)
11-118756316-C-T		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic (Nov 08, 2019)
11-118756319-T-C		Intellectual developmental disorder with impaired language and dysmorphic facies	Pathogenic (Nov 08, 2019)
11-118757229-G-A		Intellectual developmental disorder with impaired language and dysmorphic facies	Likely pathogenic (Jan 05, 2022)
11-118757245-G-A		DDX6-related disorder	Uncertain significance (Apr 18, 2023)
11-118757250-G-C		not specified	Uncertain significance (May 04, 2022)
11-118757270-C-A			Likely benign (Mar 01, 2023)
11-118758811-C-T		Intellectual developmental disorder with impaired language and dysmorphic facies	Uncertain significance (Sep 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDX6	protein_coding	protein_coding	ENST00000264018	12	41825

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000357	121730	0	1	121731	0.00000411

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.78	89	261	0.341	0.0000133	3188
Missense in Polyphen		5	80.843	0.061848		938
Synonymous	0.239	86	88.9	0.968	0.00000443	907
Loss of Function	4.65	1	27.2	0.0368	0.00000156	305

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000484	0.0000484
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In the process of mRNA degradation, plays a role in mRNA decapping (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degration of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:26098573}.
• Disease: DISEASE: Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
• Pathway: RNA degradation - Homo sapiens (human);Metabolism of RNA;EGFR1;mRNA decay by 5, to 3, exoribonuclease;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.571
• hipred: Y
• hipred_score: 0.673
• ghis: 0.513

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ddx6

Zebrafish Information Network

• Gene name: ddx6
• Affected structure: trunk vasculature
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: viral RNA genome packaging;stem cell population maintenance;cytoplasmic mRNA processing body assembly;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;negative regulation of neuron differentiation;spermatid differentiation
• Cellular component: heterochromatin;P-body;outer dense fiber;nucleus;nucleolus;cytoplasm;mitochondrion;cytosol;cell-cell adherens junction;cytoplasmic stress granule;membrane;RISC complex;chromatoid body;cytoplasmic ribonucleoprotein granule;perinuclear region of cytoplasm;concave side of sperm head;sperm annulus
• Molecular function: RNA binding;RNA helicase activity;helicase activity;protein binding;ATP binding;protein domain specific binding;cadherin binding