MYD88

MYD88 innate immune signal transduction adaptor, the group of TIR domain containing|My-T-BRC complex

Basic information

Region (hg38): 3:38138552-38143024

Links

ENSG00000172936 ∙ NCBI:4615 ∙ OMIM:602170 ∙ HGNC:7562 ∙ Uniprot:Q99836 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyogenic bacterial infections due to MyD88 deficiency (Moderate), mode of inheritance: AR
• pyogenic bacterial infections due to MyD88 deficiency (Supportive), mode of inheritance: AR
• pyogenic bacterial infections due to MyD88 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 68	AR	Allergy/Immunology/Infectious	Individuals have been reported as being susceptible to severe and recurrent pyogenic bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	18669862; 21057262; 21734245

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYD88 gene.

• Pyogenic bacterial infections due to MyD88 deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYD88 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				36	2	38
missense			54	3	3	60
nonsense	1		2			3
start loss						0
frameshift	1					1
inframe indel		1				1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	5		6
non coding			8	20	1	29
Total	2	2	64	59	6

Variants in MYD88

This is a list of pathogenic ClinVar variants found in the MYD88 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-38138662-A-G		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (May 06, 2022)
3-38138670-C-G		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Nov 27, 2023)
3-38138670-CGACCGCGCTGAGGCTCCAG-C		Pyogenic bacterial infections due to MyD88 deficiency • MYD88-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
3-38138671-G-A		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Feb 22, 2020)
3-38138671-G-T		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Jul 05, 2022)
3-38138672-A-C		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Apr 30, 2023)
3-38138675-G-C		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Apr 11, 2021)
3-38138675-G-T		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Jul 17, 2021)
3-38138685-T-G		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Oct 19, 2022)
3-38138692-C-G		not specified • Pyogenic bacterial infections due to MyD88 deficiency • Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
3-38138693-C-G		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Aug 09, 2019)
3-38138694-G-C		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Aug 04, 2023)
3-38138700-C-T		MYD88-related disorder	Likely benign (Jun 08, 2023)
3-38138706-T-C		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Sep 20, 2022)
3-38138731-G-A		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Jul 11, 2022)
3-38138736-C-G		Pyogenic bacterial infections due to MyD88 deficiency • MYD88-related disorder	Benign (Jan 19, 2024)
3-38138738-C-A		not specified	not provided (Sep 19, 2013)
3-38138738-C-G		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Aug 31, 2021)
3-38138748-C-T		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Jul 17, 2023)
3-38138762-C-G		Pyogenic bacterial infections due to MyD88 deficiency	Uncertain significance (Apr 14, 2021)
3-38138763-C-T		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Oct 03, 2023)
3-38138766-G-T		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Nov 24, 2023)
3-38138775-C-T		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (May 10, 2022)
3-38138780-T-C		not specified • Pyogenic bacterial infections due to MyD88 deficiency • MYD88-related disorder	Benign (Feb 01, 2024)
3-38138793-C-A		Pyogenic bacterial infections due to MyD88 deficiency	Likely benign (Oct 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYD88	protein_coding	protein_coding	ENST00000417037	5	4545

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.124	0.871	125658	0	90	125748	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	143	186	0.770	0.0000105	2029
Missense in Polyphen		35	61.937	0.56509		684
Synonymous	-0.556	83	76.8	1.08	0.00000415	673
Loss of Function	2.47	4	14.0	0.286	7.64e-7	143

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000510	0.000480
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.000737	0.000624
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000603	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:24316379, PubMed:19506249). Increases IL-8 transcription (PubMed:9013863). Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine (By similarity). {ECO:0000250|UniProtKB:P22366, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:19506249, ECO:0000269|PubMed:24316379, ECO:0000269|PubMed:9013863}.
• Disease: DISEASE: MYD88 deficiency (MYD88D) [MIM:612260]: Patients suffer from autosomal recessive, life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, and die between 1 and 11 months of age. Surviving patients are otherwise healthy, with normal resistance to other microbes, and their clinical status improved with age. {ECO:0000269|PubMed:18669862, ECO:0000269|PubMed:19506249, ECO:0000269|PubMed:21057262, ECO:0000269|PubMed:24316379}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in MYD88 are frequently found in many hematological malignancies, such as activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL), Waldenstroem's macroglobulinemia, cutaneous diffuse large B cell lymphoma (CBCL) and primary central nervous system lymphoma (PCNSL). {ECO:0000269|PubMed:21179087, ECO:0000269|PubMed:22931316}.
• Pathway: Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);Influenza A - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis Modulation and Signaling;IL-1 signaling pathway;AGE-RAGE pathway;Integrated Lung Cancer Pathway;Structural Pathway of Interleukin 1 (IL-1);IL1 and megakaryocytes in obesity;TLR4 Signaling and Tolerance;Toll-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;Fibrin Complement Receptor 3 Signaling Pathway;Toll-like Receptor Signaling Pathway;RAGE;TLR NFkB;Toll Like Receptor 7/8 (TLR7/8) Cascade;Signal Transduction;Signaling by Interleukins;p75NTR signals via NF-kB;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;signal transduction through il1r;nf-kb signaling pathway;nfkb activation by nontypeable hemophilus influenzae;toll-like receptor pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;TRAF6 mediated IRF7 activation;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;DEx/H-box helicases activate type I IFN and inflammatory cytokines production ;Interleukin-1 signaling;Innate Immune System;Immune System;Adaptive Immune System;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;IL-1 NFkB;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;IL-1 p38;IL-1 JNK;IL1;TLR p38;RIP-mediated NFkB activation via ZBP1;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;PIP3 activates AKT signaling;p75NTR recruits signalling complexes;Death Receptor Signalling;p75 NTR receptor-mediated signalling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;ER-Phagosome pathway;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TLR JNK;Cytosolic sensors of pathogen-associated DNA ;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Intracellular signaling by second messengers;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Endogenous TLR signaling;p75(NTR)-mediated signaling;IL1-mediated signaling events;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.267
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.180
• hipred: Y
• hipred_score: 0.783
• ghis: 0.630

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myd88
• Phenotype: neoplasm; 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); 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); hematopoietic system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: myd88
• Affected structure: T cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: toll-like receptor signaling pathway;MyD88-dependent toll-like receptor signaling pathway;apoptotic process;inflammatory response;signal transduction;cell surface receptor signaling pathway;positive regulation of gene expression;positive regulation of type I interferon production;positive regulation of interleukin-17 production;positive regulation of interleukin-23 production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 production;toll-like receptor 9 signaling pathway;defense response to bacterium;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;regulation of inflammatory response;defense response to Gram-positive bacterium;positive regulation of NF-kappaB transcription factor activity;type I interferon signaling pathway;interleukin-1-mediated signaling pathway;response to interleukin-1;3'-UTR-mediated mRNA stabilization;cellular response to mechanical stimulus;cellular response to oxidised low-density lipoprotein particle stimulus;positive regulation of cytokine production involved in inflammatory response
• Cellular component: nucleus;cytoplasm;cytosol;plasma membrane;endosome membrane
• Molecular function: death receptor binding;protein binding;identical protein binding;protein self-association;TIR domain binding