DDX11

DEAD/H-box helicase 11, the group of DEAD-box helicases|DNA helicases

Basic information

Region (hg38): 12:31073860-31104799

Links

ENSG00000013573 ∙ NCBI:1663 ∙ OMIM:601150 ∙ HGNC:2736 ∙ Uniprot:Q96FC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Warsaw breakage syndrome (Definitive), mode of inheritance: AR
• Warsaw breakage syndrome (Supportive), mode of inheritance: AD
• Warsaw breakage syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warsaw breakage syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	20137776; 23033317

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDX11 gene.

• Inborn_genetic_diseases (162 variants)
• not_provided (92 variants)
• Warsaw_breakage_syndrome (60 variants)
• not_specified (15 variants)
• DDX11-related_condition (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDX11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030653.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	2	36
missense		3	166	16	7	192
nonsense	3	8	1			12
start loss						0
frameshift	1	13	3			17
splice donor/acceptor (+/-2bp)	6	10	1	2		19
Total	10	34	172	51	9

Highest pathogenic variant AF is 0.0019139058

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDX11	protein_coding	protein_coding	ENST00000407793	26	30947

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.35e-21	0.294	125429	0	319	125748	0.00127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.221	573	558	1.03	0.0000352	6253
Missense in Polyphen		193	190.99	1.0105		2249
Synonymous	0.180	218	221	0.985	0.0000144	1891
Loss of Function	1.79	40	54.2	0.738	0.00000302	587

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00322	0.00284
Ashkenazi Jewish	0.00853	0.00857
East Asian	0.00138	0.00136
Finnish	0.000656	0.000647
European (Non-Finnish)	0.000955	0.000941
Middle Eastern	0.00138	0.00136
South Asian	0.000593	0.000588
Other	0.000994	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis (PubMed:10648783, PubMed:21854770, PubMed:23797032, PubMed:26089203, PubMed:26503245). Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single- stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction (PubMed:18499658, PubMed:22102414). The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities (PubMed:18499658). Shows also ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three- stranded D-loop DNA molecules (PubMed:22102414, PubMed:26503245). Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage (PubMed:23797032). Recruited with TIMELESS factor upon DNA- replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (PubMed:26503245). Cooperates also with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17105772, PubMed:18499658, PubMed:20124417, PubMed:23116066, PubMed:23797032). Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis (PubMed:18499658). Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (PubMed:27477908). Plays also a role in heterochromatin organization (PubMed:21854770). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203). Plays a role in embryonic development and prevention of aneuploidy (By similarity). Involved in melanoma cell proliferation and survival (PubMed:23116066). Associates with chromatin at DNA replication fork regions (PubMed:27477908). Binds to single- and double- stranded DNAs (PubMed:9013641, PubMed:18499658, PubMed:22102414). {ECO:0000250|UniProtKB:Q6AXC6, ECO:0000269|PubMed:10648783, ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:20124417, ECO:0000269|PubMed:21854770, ECO:0000269|PubMed:22102414, ECO:0000269|PubMed:23116066, ECO:0000269|PubMed:23797032, ECO:0000269|PubMed:26089203, ECO:0000269|PubMed:26503245, ECO:0000269|PubMed:27477908}.
• Disease: DISEASE: Warsaw breakage syndrome (WBRS) [MIM:613398]: A syndrome characterized by severe microcephaly, pre- and postnatal growth retardation, facial dysmorphism and abnormal skin pigmentation. Additional features include high arched palate, coloboma of the right optic disk, deafness, ventricular septal defect, toes and fingers abnormalities. At cellular level, drug-induced chromosomal breakage, a feature of Fanconi anemia, and sister chromatid cohesion defects, a feature of Roberts syndrome, coexist. {ECO:0000269|PubMed:20137776, ECO:0000269|PubMed:23033317, ECO:0000269|PubMed:26089203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: XBP1(S) activates chaperone genes (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.774
• rvis_EVS: 1.03
• rvis_percentile_EVS: 91.11

Haploinsufficiency Scores

• pHI: 0.186
• hipred: Y
• hipred_score: 0.604
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddx11
• Phenotype: embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ddx11
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved caudal

Gene ontology

• Biological process: DNA repair;cellular response to DNA damage stimulus;sister chromatid cohesion;multicellular organism development;viral process;replication fork processing;positive regulation of endodeoxyribonuclease activity;negative regulation of protein binding;DNA duplex unwinding;establishment of sister chromatid cohesion;positive regulation of chromatin binding;IRE1-mediated unfolded protein response;G-quadruplex DNA unwinding;positive regulation of sister chromatid cohesion;cellular response to hydroxyurea;cellular response to cisplatin;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I;cellular response to bleomycin;nucleolar chromatin organization;positive regulation of double-strand break repair
• Cellular component: nuclear chromatin;spindle pole;fibrillar center;nucleus;nucleoplasm;nucleolus;cytoplasm;centrosome;midbody;mitotic cohesin complex;Ctf18 RFC-like complex;extracellular exosome
• Molecular function: DNA binding;chromatin binding;DNA replication origin binding;double-stranded DNA binding;single-stranded DNA binding;single-stranded RNA binding;ATP-dependent DNA helicase activity;helicase activity;protein binding;ATP binding;ATP-dependent helicase activity;DNA-dependent ATPase activity;RNA-dependent ATPase activity;triplex DNA binding;metal ion binding;4 iron, 4 sulfur cluster binding;G-quadruplex DNA binding