DDX41

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

Basic information

Region (hg38): 5:177511576-177516961

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

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.

• not provided (284 variants)
• DDX41-related hematologic malignancy predisposition syndrome (95 variants)
• not specified (60 variants)
• DDX41-related condition (14 variants)
• Inborn genetic diseases (14 variants)
• Bone marrow hypocellularity (3 variants)
• Acute myeloid leukemia (3 variants)
• Myelodysplasia (2 variants)
• - (2 variants)
• Inherited acute myeloid leukemia (1 variants)
• Myelodysplastic syndrome (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.

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			14	40	5	59
missense		7	139	1		147
nonsense	10	5				15
start loss	1	1				2
frameshift	11	9				20
inframe indel		1				1
splice donor/acceptor (+/-2bp)	1	6				7
splice region	1		12	9	5	27
non coding		1	8	35	17	61
Total	23	30	161	76	22

Highest pathogenic variant AF is 0.0000658

Variants in DDX41

This is a list of pathogenic ClinVar variants found in the DDX41 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-177511597-T-C		not specified	Uncertain significance (Apr 20, 2020)
5-177511610-G-C		not specified	Uncertain significance (Apr 03, 2018)
5-177511694-G-A			Likely benign (Mar 27, 2019)
5-177511717-G-A		not specified	Benign/Likely benign (Jun 21, 2019)
5-177511728-A-G		not specified	Uncertain significance (Oct 24, 2019)
5-177511788-G-A		not specified • DDX41-related disorder	Benign/Likely benign (Apr 22, 2022)
5-177511790-C-T		DDX41-related disorder	Likely benign (Jan 30, 2023)
5-177511792-C-T			Uncertain significance (Dec 04, 2022)
5-177511806-G-A			Likely benign (Sep 22, 2023)
5-177511810-T-C		DDX41-related disorder • DDX41-related hematologic malignancy predisposition syndrome	Uncertain significance (Jun 09, 2023)
5-177511824-C-T			Likely benign (Oct 09, 2023)
5-177511832-C-T			Uncertain significance (Sep 21, 2022)
5-177511833-G-A		not specified	Likely benign (Nov 25, 2023)
5-177511866-G-A			Likely benign (Jul 17, 2023)
5-177511871-T-C			Uncertain significance (Sep 23, 2022)
5-177511901-C-A		DDX41-related hematologic malignancy predisposition syndrome	Uncertain significance (Dec 22, 2020)
5-177511905-G-A			Likely benign (Sep 15, 2022)
5-177511920-G-A			Likely benign (Jul 17, 2023)
5-177511921-C-T			Uncertain significance (Aug 09, 2023)
5-177511930-G-A			Uncertain significance (Jan 24, 2024)
5-177511943-CA-C			Likely benign (Apr 25, 2023)
5-177511943-CAG-C			Likely benign (Dec 06, 2023)
5-177511947-G-A			Likely benign (Mar 21, 2023)
5-177512050-T-C			Benign (Apr 03, 2019)
5-177512077-G-T			Benign (Sep 27, 2023)

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

• 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