immunodeficiency 123 with HPV-related verrucosis

Summary

immunodeficiency 123 with HPV-related verrucosis (MONDO:0971177) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 123 with HPV-related verrucosis
Mondo ID	MONDO:0971177
OMIM	620901
DOID	DOID:0061089
UMLS	C5935639
MedGen	1855052
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 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 › immunodeficiency 123 with HPV-related verrucosis

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3256912	NM_006139.4(CD28):c.52G>A (p.Gly18Arg)	CD28	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
CD28	Moderate	Autosomal recessive	immunodeficiency 123 with HPV-related verrucosis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD28	Orphanet:2584	Classic mycosis fungoides
CD28	Orphanet:3162	Sézary syndrome

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
CD28	HGNC:1653	ENSG00000178562	P10747	T-cell-specific surface glycoprotein CD28	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD28	T-cell-specific surface glycoprotein CD28	Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis.

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)
CD28	Antibody/Immunoglobulin	yes		CD28, Ig_V-set, Ig-like_fold

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
blood	1
lymph node	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD28	154	broad	marker	lymph node, vermiform appendix, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD28	2,958

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD28	P10747	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
Nef mediated downregulation of CD28 cell surface expression	1	5710.0×	0.004	CD28
CD28 dependent Vav1 pathway	1	878.5×	0.007	CD28
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.007	CD28
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.007	CD28
Regulation of T cell activation by CD28 family	1	423.0×	0.007	CD28
CD28 dependent PI3K/Akt signaling	1	393.8×	0.007	CD28
Co-stimulation by CD28	1	380.7×	0.007	CD28
PI3K/AKT Signaling in Cancer	1	368.4×	0.007	CD28
Host Interactions of HIV factors	1	335.9×	0.007	CD28
Negative regulation of the PI3K/AKT network	1	278.5×	0.008	CD28
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.015	CD28
HIV Infection	1	119.0×	0.015	CD28
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.017	CD28
Intracellular signaling by second messengers	1	91.4×	0.017	CD28
PIP3 activates AKT signaling	1	66.8×	0.022	CD28
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.024	CD28
Viral Infection Pathways	1	30.8×	0.041	CD28
Adaptive Immune System	1	29.8×	0.041	CD28
Infectious disease	1	24.8×	0.047	CD28
Disease	1	13.1×	0.081	CD28
Immune System	1	13.0×	0.081	CD28
Signal Transduction	1	10.2×	0.098	CD28

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
positive regulation of inflammatory response to antigenic stimulus	1	5617.3×	0.003	CD28
regulatory T cell differentiation	1	2106.5×	0.003	CD28
CD4-positive, alpha-beta T cell proliferation	1	1872.4×	0.003	CD28
regulation of regulatory T cell differentiation	1	1872.4×	0.003	CD28
positive regulation of CD4-positive, alpha-beta T cell proliferation	1	1685.2×	0.003	CD28
positive regulation of isotype switching to IgG isotypes	1	1532.0×	0.003	CD28
negative thymic T cell selection	1	1404.3×	0.003	CD28
positive regulation of T cell receptor signaling pathway	1	766.0×	0.005	CD28
positive regulation of viral genome replication	1	581.1×	0.005	CD28
positive regulation of interleukin-4 production	1	561.7×	0.005	CD28
positive regulation of mitotic nuclear division	1	543.6×	0.005	CD28
positive regulation of interleukin-2 production	1	468.1×	0.005	CD28
positive regulation of interleukin-10 production	1	401.2×	0.006	CD28
T cell costimulation	1	374.5×	0.006	CD28
humoral immune response	1	280.9×	0.006	CD28
positive regulation of cytokine production	1	271.8×	0.006	CD28
positive regulation of T cell proliferation	1	259.3×	0.006	CD28
T cell activation	1	259.3×	0.006	CD28
positive regulation of translation	1	227.7×	0.006	CD28
apoptotic signaling pathway	1	224.7×	0.006	CD28
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	CD28
T cell receptor signaling pathway	1	151.8×	0.009	CD28
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.016	CD28
transcription by RNA polymerase II	1	70.5×	0.017	CD28
negative regulation of gene expression	1	69.1×	0.017	CD28
cell surface receptor signaling pathway	1	64.1×	0.017	CD28
positive regulation of gene expression	1	38.7×	0.028	CD28
negative regulation of apoptotic process	1	34.8×	0.030	CD28
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	CD28

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
CD28	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
CD28	1	Functional:1

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	CD28
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)
CD28	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.