CD4

Chr 12AR

CD4 molecule

Also known as: CD4mut, IMD79, Leu-3, OKT4D, T4

NCBI Gene: 920 ENSG00000010610 UniProt: P01730 OMIM: 186940

The CD4 protein functions as a membrane glycoprotein coreceptor that works with the T-cell receptor to recognize antigens presented by MHC class II molecules, playing an essential role in T-helper cell activation and immune responses. Mutations cause autosomal recessive immunodeficiency disorders including Immunodeficiency 79 and OKT4 epitope deficiency, affecting the immune system's ability to mount appropriate responses to pathogens. The gene shows low constraint against loss-of-function variants (pLI 0.0008), consistent with recessive inheritance where one functional copy provides sufficient protein function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 79MIM #619238

OKT4 epitope deficiencyMIM #613949

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Immunodeficiency 79; OKT4 epitope deficiency; no ClinGen or GenCC tier

Active trials

14874

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CD4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.001

Z-score 2.59

OE 0.41 (0.24–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.06Z-score

OE missense 0.81 (0.72–0.91)

206 obs / 253.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.24–0.71)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 22.1Missense obs/exp: 206 / 253.3Syn Z: 0.34

Background carrier burden — how many people carry a rare variant somewhere in CD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

496 rare PASS variants

Rare truncating (LoF)

1 in 2,700

70 rare PASS variants

Rare synonymous (reference)

1 in 140

225 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 3,100
South Asian	~43k	1 in 73	1 in 8,400
Remaining (unassigned)	~30k	1 in 85	1 in 780
European (Finnish)	~27k	1 in 200	≈ 1 in 8,700
Admixed American	~22k	1 in 120	1 in 1,400
African / African American	~21k	1 in 110	1 in 2,300
East Asian	~20k	1 in 150	1 in 4,000
Ashkenazi Jewish	~13k	1 in 260	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓