CD4

CD4 molecule, the group of V-set domain containing|CD molecules|C2-set domain containing

Basic information

Region (hg38): 12:6786858-6820799

Links

ENSG00000010610 ∙ NCBI:920 ∙ OMIM:186940 ∙ HGNC:1678 ∙ Uniprot:P01730 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 79 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the CD4 gene.

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.

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				7	5	12
missense			10	1	4	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					8	8
Total	0	0	10	8	17

Variants in CD4

This is a list of pathogenic ClinVar variants found in the CD4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-6800139-A-G		Immunodeficiency 79	Pathogenic (Mar 26, 2021)
12-6800214-TG-T		Immunodeficiency 79 • not specified	Benign (Jan 24, 2024)
12-6800222-A-G		Immunodeficiency 79 • not specified	Benign (Jan 24, 2024)
12-6800276-T-C		not specified	Benign (Jan 24, 2024)
12-6814296-C-A		not specified	Uncertain significance (Feb 22, 2023)
12-6814296-C-T			Benign (May 31, 2018)
12-6814942-T-C		not specified	Uncertain significance (Jan 18, 2023)
12-6814956-A-G			Benign (May 29, 2018)
12-6815983-C-T		not specified • CD4-related disorder	Benign (Jan 24, 2024)
12-6816124-G-A		not specified	Likely benign (Jan 17, 2024)
12-6816128-T-C			Benign (Jul 06, 2018)
12-6816147-G-A			Likely benign (May 18, 2018)
12-6816147-G-T			Benign (Jul 06, 2018)
12-6816156-C-T			Likely benign (Feb 01, 2023)
12-6816159-G-A		CD4-related disorder	Benign/Likely benign (Nov 01, 2022)
12-6816241-C-T		Okt4 epitope deficiency • not specified • CD4-related disorder	Benign (Oct 28, 2020)
12-6816247-A-G		Okt4 epitope deficiency • Immunodeficiency 79;Okt4 epitope deficiency	Uncertain significance (Dec 22, 2021)
12-6816372-G-A			Likely benign (Apr 01, 2023)
12-6817156-T-C		not specified	Uncertain significance (May 31, 2022)
12-6817194-G-C			Likely benign (May 18, 2018)
12-6817197-T-C		Immunodeficiency 79 • not specified	Benign (Jan 24, 2024)
12-6817204-C-T		CD4-related disorder	Likely benign (Feb 22, 2019)
12-6817229-C-G		not specified	Uncertain significance (Sep 15, 2021)
12-6817254-G-A		CD4-related disorder	Likely benign (Nov 16, 2019)
12-6817256-T-C		not specified	Uncertain significance (Jun 23, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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