CD4
CD4 molecule, the group of V-set domain containing|CD molecules|C2-set domain containing
Basic information
Region (hg38): 12:6786858-6820799
Links
Phenotypes
GenCC
Source:
- immunodeficiency 79 (Limited), mode of inheritance: Unknown
- immunodeficiency 79 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 79 | AR | Allergy/Immunology/Infectious | The condition may involve early-onset and severe HPV, respiratory, and other infections, and awareness may allow early and agressive treatment of infections, as well as potential preventative measures | Allergy/Immunology/Infectious | 6790623; 6209207; 6199335; 6199366; 6229573; 6208600; 1708753; 1961196; 7534484; 7541811; 7689618; 31781092; 33471124 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (17 variants)
- not_provided (12 variants)
- Immunodeficiency_79 (4 variants)
- CD4-related_disorder (4 variants)
- Okt4_epitope_deficiency (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000616.5. 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 | 11 | |||||
| missense | 15 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 2 | 0 | 15 | 9 | 7 |
Highest pathogenic variant AF is 0.000016110183
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CD4 | protein_coding | protein_coding | ENST00000011653 | 9 | 33951 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000789 | 0.996 | 125738 | 0 | 10 | 125748 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.06 | 206 | 253 | 0.813 | 0.0000136 | 2959 |
| Missense in Polyphen | 52 | 79.005 | 0.65819 | 1024 | ||
| Synonymous | 0.345 | 101 | 106 | 0.957 | 0.00000589 | 904 |
| Loss of Function | 2.59 | 9 | 22.1 | 0.406 | 9.94e-7 | 253 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000449 | 0.0000439 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T- helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. {ECO:0000269|PubMed:16951326, ECO:0000269|PubMed:24942581, ECO:0000269|PubMed:2823150}.;
- Pathway
- Antigen processing and presentation - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;TYROBP Causal Network;Cytokines and Inflammatory Response;T-Cell antigen Receptor (TCR) Signaling Pathway;Disease;Other interleukin signaling;Signaling by Interleukins;Vesicle-mediated transport;hiv-1 defeats host-mediated resistance by cem15;lck and fyn tyrosine kinases in initiation of tcr activation;role of mef2d in t-cell apoptosis;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;t cell receptor signaling pathway;Membrane Trafficking;Cytokine Signaling in Immune system;Phosphorylation of CD3 and TCR zeta chains;Generation of second messenger molecules;HIV Life Cycle;Host Interactions of HIV factors;HIV Infection;Translocation of ZAP-70 to Immunological synapse;Downstream TCR signaling;TCR signaling;IL12 signaling mediated by STAT4;PD-1 signaling;Costimulation by the CD28 family;CD4 T cell receptor signaling-ERK cascade;TCR;Infectious disease;Antimicrobial peptides;Innate Immune System;Immune System;Binding and entry of HIV virion;Adaptive Immune System;Alpha-defensins;Defensins;Clathrin-mediated endocytosis;CXCR4-mediated signaling events;Nef Mediated CD4 Down-regulation;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis;Arf1 pathway;C-MYB transcription factor network;Cargo recognition for clathrin-mediated endocytosis;Vpu mediated degradation of CD4;Notch-mediated HES/HEY network;IL23-mediated signaling events;TCR signaling in naïve CD4+ T cells;IL12-mediated signaling events;Early Phase of HIV Life Cycle;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.984
Intolerance Scores
- loftool
- 0.837
- rvis_EVS
- 0.58
- rvis_percentile_EVS
- 82.17
Haploinsufficiency Scores
- pHI
- 0.447
- hipred
- Y
- hipred_score
- 0.539
- ghis
- 0.458
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.340
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cd4
- Phenotype
- immune system 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); digestive/alimentary phenotype; normal 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); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- cytokine production;positive regulation of protein phosphorylation;adaptive immune response;induction by virus of host cell-cell fusion;immune response;cell adhesion;signal transduction;cell surface receptor signaling pathway;enzyme linked receptor protein signaling pathway;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of calcium ion transport into cytosol;fusion of virus membrane with host plasma membrane;cytokine-mediated signaling pathway;T cell differentiation;entry into host cell;response to estradiol;maintenance of protein location in cell;response to vitamin D;positive regulation of kinase activity;helper T cell enhancement of adaptive immune response;interleukin-15-mediated signaling pathway;positive regulation of T cell proliferation;T cell activation;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAPK cascade;T cell selection;positive regulation of interleukin-2 biosynthetic process;positive regulation of monocyte differentiation;positive regulation of protein kinase activity;positive regulation of transcription, DNA-templated;positive regulation of viral entry into host cell;regulation of defense response to virus by virus;positive regulation of peptidyl-tyrosine phosphorylation;defense response to Gram-negative bacterium;positive regulation of calcium-mediated signaling;T cell receptor signaling pathway;regulation of T cell activation;regulation of calcium ion transport;membrane organization;positive regulation of ERK1 and ERK2 cascade;cellular response to granulocyte macrophage colony-stimulating factor stimulus
- Cellular component
- early endosome;endoplasmic reticulum lumen;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;external side of plasma membrane;clathrin-coated vesicle membrane;T cell receptor complex;membrane raft
- Molecular function
- virus receptor activity;transmembrane signaling receptor activity;extracellular matrix structural constituent;protein binding;zinc ion binding;coreceptor activity;immunoglobulin binding;enzyme binding;protein kinase binding;signaling receptor activity;interleukin-16 binding;interleukin-16 receptor activity;MHC class II protein binding;identical protein binding;protein homodimerization activity;protein tyrosine kinase binding