Immunodeficiency 79

Summary

Immunodeficiency 79 (MONDO:0030981) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 11
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 79
Mondo ID	MONDO:0030981
OMIM	619238
DOID	DOID:0112277
UMLS	C5543220
MedGen	1783683
GARD	0009523
Is cancer (heuristic)	no

Also known as: CD4 Deficiency · IMD79 · immunodeficiency 79

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › combined immunodeficiency › severe combined immunodeficiency › immunodeficiency 79

Related subtypes (10): recombinase activating gene 1 deficiency, recombinase activating gene 2 deficiency, janus kinase-3 deficiency, T-cell immunodeficiency, congenital alopecia, and nail dystrophy, T-B- severe combined immunodeficiency, severe combined immunodeficiency due to CARMIL2 deficiency, familial severe combined immunodeficiency, severe combined immunodeficiency due to CD70 deficiency, T-B+ severe combined immunodeficiency, T+ B+ severe combined immunodeficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

7 benign, 2 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1048526	NM_000616.5(CD4):c.1157-1G>A	CD4	Pathogenic	no assertion criteria provided
1048527	NM_000616.5(CD4):c.1A>G (p.Met1Val)	CD4	Pathogenic	no assertion criteria provided
2377032	NM_000616.5(CD4):c.1330A>G (p.Thr444Ala)	CD4	Uncertain significance	criteria provided, multiple submitters, no conflicts
626076	NM_000616.5(CD4):c.799A>G (p.Thr267Ala)	CD4	Uncertain significance	criteria provided, single submitter
1192704	NM_000616.5(CD4):c.49+28del	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192705	NM_000616.5(CD4):c.49+35A>G	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192706	NM_000616.5(CD4):c.1023T>C (p.Ser341=)	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192707	NM_000616.5(CD4):c.1341T>C (p.Cys447=)	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192708	NM_000616.5(CD4):c.1346+55T>G	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192709	NM_000616.5(CD4):c.*91C>A	CD4	Benign	criteria provided, multiple submitters, no conflicts
1192710	NM_000616.5(CD4):c.*92A>G	CD4	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD4	Moderate	Autosomal recessive	immunodeficiency 79	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD4	HGNC:1678	ENSG00000010610	P01730	T-cell surface glycoprotein CD4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD4	T-cell surface glycoprotein CD4	Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD4	Antibody/Immunoglobulin	yes		CD4, Ig_sub2, Ig_sub

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD4	245	broad	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD4	8,331

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD4	P01730	84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Binding and entry of HIV virion	1	2855.0×	0.006	CD4
Early Phase of HIV Life Cycle	1	1631.4×	0.006	CD4
Nef Mediated CD4 Down-regulation	1	1268.9×	0.006	CD4
Alpha-defensins	1	1038.2×	0.006	CD4
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.006	CD4
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.006	CD4
Translocation of ZAP-70 to Immunological synapse	1	634.4×	0.006	CD4
Phosphorylation of CD3 and TCR zeta chains	1	543.8×	0.006	CD4
Co-inhibition by PD-1	1	519.1×	0.006	CD4
TCR signaling	1	496.5×	0.006	CD4
Other interleukin signaling	1	475.8×	0.006	CD4
Regulation of T cell activation by CD28 family	1	423.0×	0.006	CD4
Generation of second messenger molecules	1	346.1×	0.007	CD4
Host Interactions of HIV factors	1	335.9×	0.007	CD4
Vpu mediated degradation of CD4	1	265.6×	0.008	CD4
Defensins	1	237.9×	0.008	CD4
Antimicrobial peptides	1	223.9×	0.008	CD4
HIV Life Cycle	1	160.8×	0.011	CD4
Downstream TCR signaling	1	128.3×	0.013	CD4
HIV Infection	1	119.0×	0.013	CD4
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.015	CD4
Clathrin-mediated endocytosis	1	85.2×	0.017	CD4
Signaling by Interleukins	1	64.2×	0.022	CD4
Cytokine Signaling in Immune system	1	40.8×	0.033	CD4
Membrane Trafficking	1	37.1×	0.035	CD4
Vesicle-mediated transport	1	34.8×	0.035	CD4
Viral Infection Pathways	1	30.8×	0.038	CD4
Adaptive Immune System	1	29.8×	0.038	CD4
Innate Immune System	1	25.5×	0.043	CD4
Infectious disease	1	24.8×	0.043	CD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
helper T cell enhancement of adaptive immune response	1	16852.0×	0.002	CD4
response to methamphetamine hydrochloride	1	8426.0×	0.002	CD4
T cell selection	1	5617.3×	0.002	CD4
maintenance of protein location in cell	1	3370.4×	0.002	CD4
cellular response to ionomycin	1	2808.7×	0.002	CD4
regulation of T cell activation	1	1872.4×	0.002	CD4
interleukin-15-mediated signaling pathway	1	1685.2×	0.002	CD4
positive regulation of monocyte differentiation	1	1532.0×	0.002	CD4
enzyme-linked receptor protein signaling pathway	1	1296.3×	0.002	CD4
cellular response to granulocyte macrophage colony-stimulating factor stimulus	1	1296.3×	0.002	CD4
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.002	CD4
response to vitamin D	1	802.5×	0.003	CD4
macrophage differentiation	1	468.1×	0.004	CD4
positive regulation of interleukin-2 production	1	468.1×	0.004	CD4
positive regulation of calcium-mediated signaling	1	421.3×	0.004	CD4
symbiont entry into host cell	1	401.2×	0.004	CD4
T cell differentiation	1	383.0×	0.004	CD4
positive regulation of T cell proliferation	1	259.3×	0.006	CD4
response to estradiol	1	198.3×	0.008	CD4
calcium-mediated signaling	1	183.2×	0.008	CD4
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.008	CD4
defense response to Gram-negative bacterium	1	168.5×	0.008	CD4
T cell receptor signaling pathway	1	151.8×	0.008	CD4
response to ethanol	1	146.5×	0.008	CD4
adaptive immune response	1	84.3×	0.014	CD4
cell surface receptor signaling pathway	1	64.1×	0.017	CD4
immune response	1	47.1×	0.023	CD4
cell adhesion	1	37.5×	0.028	CD4
signal transduction	1	16.1×	0.062	CD4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CD4	38	Binding:30, Functional:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CD4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CD4	38	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06044792	Not specified	NOT_YET_RECRUITING	The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
NCT02135003	Not specified	COMPLETED	Non-enrolment and Non-adherence to HIV Care in a Community-based Program, Rakai, Uganda