DDX41

DEAD-box helicase 41, the group of DEAD-box helicases|Spliceosomal C complex|Spliceosomal P complex

Basic information

Region (hg38): 5:177511577-177516961

Links

ENSG00000183258

∙ NCBI:51428 ∙ OMIM:608170 ∙ HGNC:18674 ∙ Uniprot:Q9UJV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

DDX41-related hematologic malignancy predisposition syndrome (Strong), mode of inheritance: AD
DDX41-related hematologic malignancy predisposition syndrome (Strong), mode of inheritance: AD
DDX41-related hematologic malignancy predisposition syndrome (Definitive), mode of inheritance: AD
DDX41-related hematologic malignancy predisposition syndrome (Definitive), mode of inheritance: AD
acromesomelic dysplasia (Limited), mode of inheritance: AR
DDX41-related hematologic malignancy predisposition syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Familial myeloproliferative/lymphoproliferative neoplasms, multiple types, susceptibility to	AD	Oncologic	Among other findings, individuals have been described with hematologic malignancies, and awareness may allow early detection and management	Allergy/Immunology/Infectious; Oncologic	25920683; 26712909

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDX41 gene.

Inborn_genetic_diseases (788 variants)
not_provided (551 variants)
DDX41-related_hematologic_malignancy_predisposition_syndrome (209 variants)
DDX41-related_disorder (69 variants)
not_specified (56 variants)
Acute_myeloid_leukemia (4 variants)
Myelodysplasia (3 variants)
Bone_marrow_hypocellularity (3 variants)
Myelodysplastic_syndrome (1 variants)
Hereditary_cancer-predisposing_syndrome (1 variants)
Aplastic_anemia (1 variants)
Inherited_acute_myeloid_leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDX41 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016222.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			15 clinvar	293 clinvar		308
missense	4 clinvar	26 clinvar	413 clinvar	62 clinvar	1 clinvar	506
nonsense	14 clinvar	10 clinvar	1 clinvar			25
start loss	2	1				3
frameshift	31 clinvar	19 clinvar	3 clinvar			53
splice donor/acceptor (+/-2bp)	2 clinvar	23 clinvar	6 clinvar			31
Total	53	79	438	355	1

Highest pathogenic variant AF is 0.000200757

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDX41	protein_coding	protein_coding	ENST00000507955	17	5893

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.59e-8	0.998	125659	0	89	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	272	401	0.679	0.0000253	4056
Missense in Polyphen		67	112.95	0.59317		1189
Synonymous	-2.77	199	155	1.28	0.0000102	1201
Loss of Function	2.81	18	36.3	0.496	0.00000190	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000547	0.000547
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000481	0.000466
Middle Eastern	0.000544	0.000544
South Asian	0.000327	0.000327
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probable ATP-dependent RNA helicase. Is required during post-transcriptional gene expression. May be involved in pre-mRNA splicing. {ECO:0000269|PubMed:25920683}.;
Disease: DISEASE: Myeloproliferative/lymphoproliferative neoplasms, familial (MPLPF) [MIM:616871]: A familial cancer predisposition syndrome with incomplete penetrance, characterized by increased susceptibility to myeloid neoplasms and rarely to lymphoid malignancies. MPLPF inheritance is autosomal dominant. {ECO:0000269|PubMed:25920683, ECO:0000269|PubMed:26712909}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway: STING mediated induction of host immune responses;Regulation of innate immune responses to cytosolic DNA;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;Cytosolic sensors of pathogen-associated DNA (Consensus)

Recessive Scores

pRec: 0.258

Intolerance Scores

loftool
rvis_EVS: -1.09
rvis_percentile_EVS: 7.05

Haploinsufficiency Scores

pHI: 0.225
hipred: Y
hipred_score: 0.603
ghis: 0.638

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.733

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ddx41
Phenotype: 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);

Zebrafish Information Network

Gene name: ddx41
Affected structure: positive regulation of NIK/NF-kappaB signaling
Phenotype tag: abnormal
Phenotype quality: disrupted

Gene ontology

Biological process: mRNA splicing, via spliceosome;apoptotic process;cell population proliferation;cell differentiation;positive regulation of type I interferon production;cellular response to interferon-beta;positive regulation of transcription by RNA polymerase II;defense response to virus
Cellular component: nucleus;spliceosomal complex;endoplasmic reticulum;cytosol;membrane;catalytic step 2 spliceosome
Molecular function: DNA binding;RNA binding;helicase activity;protein binding;ATP binding;metal ion binding