Immunodeficiency 97 with autoinflammation

Summary

Immunodeficiency 97 with autoinflammation (MONDO:0030717) is a disease caused by PIK3CG (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PIK3CG (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 97 with autoinflammation
Mondo ID	MONDO:0030717
OMIM	619802
DOID	DOID:0061067
UMLS	C5676946
MedGen	1802936
Is cancer (heuristic)	no

Also known as: IMD97 · immunodeficiency 97 with autoinflammation

Data availability: 9 ClinVar variants · 4 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 97 with autoinflammation

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 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 123 with HPV-related verrucosis, 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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 uncertain significance, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3775985	NM_001282426.2(PIK3CG):c.[391_397del;456_468del]		Pathogenic	criteria provided, single submitter
1675218	NM_001282426.2(PIK3CG):c.3062G>C (p.Arg1021Pro)	PIK3CG	Pathogenic	no assertion criteria provided
1675219	NM_001282426.2(PIK3CG):c.3254A>G (p.Asn1085Ser)	PIK3CG	Pathogenic	no assertion criteria provided
1675220	NM_001282426.2(PIK3CG):c.145C>A (p.Arg49Ser)	PIK3CG	Pathogenic	no assertion criteria provided
3257910	NM_001282426.2(PIK3CG):c.2545C>T (p.Arg849Ter)	PIK3CG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1675217	NM_001282426.2(PIK3CG):c.2944del (p.Arg982fs)	PIK3CG	Uncertain significance	criteria provided, single submitter
4056726	NM_001282426.2(PIK3CG):c.1568dup (p.Tyr523Ter)	PIK3CG	Uncertain significance	criteria provided, single submitter
4293086	NM_001282426.2(PIK3CG):c.3007A>G (p.Ser1003Gly)	PIK3CG	Uncertain significance	criteria provided, single submitter
1331023	NM_001282426.2(PIK3CG):c.1565A>G (p.Asn522Ser)	PIK3CG	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PIK3CG	Strong	Autosomal recessive	immunodeficiency 97 with autoinflammation	4

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
PIK3CG	HGNC:8978	ENSG00000105851	P48736	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIK3CG	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3).

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIK3CG	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

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
bone marrow	1
bone marrow cell	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIK3CG	201	broad	marker	bone marrow, trabecular bone tissue, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3CG	2,964

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CG	P48736	107

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Co-stimulation by ICOS	1	1038.2×	0.005	PIK3CG
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	951.7×	0.005	PIK3CG
G beta:gamma signalling through PI3Kgamma	1	439.2×	0.006	PIK3CG
CD28 dependent PI3K/Akt signaling	1	393.8×	0.006	PIK3CG
GPVI-mediated activation cascade	1	308.6×	0.006	PIK3CG
Synthesis of PIPs at the plasma membrane	1	211.5×	0.007	PIK3CG
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.010	PIK3CG
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	PIK3CG
PIP3 activates AKT signaling	1	66.8×	0.015	PIK3CG

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
natural killer cell chemotaxis	1	8426.0×	0.002	PIK3CG
secretory granule localization	1	5617.3×	0.002	PIK3CG
respiratory burst involved in defense response	1	4213.0×	0.002	PIK3CG
negative regulation of cardiac muscle contraction	1	4213.0×	0.002	PIK3CG
negative regulation of triglyceride catabolic process	1	2808.7×	0.002	PIK3CG
neutrophil extravasation	1	2808.7×	0.002	PIK3CG
negative regulation of fibroblast apoptotic process	1	2407.4×	0.002	PIK3CG
regulation of calcium ion transmembrane transport	1	2106.5×	0.002	PIK3CG
regulation of cell adhesion mediated by integrin	1	1872.4×	0.002	PIK3CG
sphingosine-1-phosphate receptor signaling pathway	1	1685.2×	0.002	PIK3CG
positive regulation of acute inflammatory response	1	1404.3×	0.003	PIK3CG
phosphatidylinositol-3-phosphate biosynthetic process	1	1296.3×	0.003	PIK3CG
T cell chemotaxis	1	1123.5×	0.003	PIK3CG
hepatocyte apoptotic process	1	1053.2×	0.003	PIK3CG
dendritic cell chemotaxis	1	991.3×	0.003	PIK3CG
phosphatidylinositol-mediated signaling	1	702.2×	0.003	PIK3CG
positive regulation of Rac protein signal transduction	1	648.1×	0.003	PIK3CG
positive regulation of MAP kinase activity	1	648.1×	0.003	PIK3CG
mast cell degranulation	1	624.1×	0.003	PIK3CG
phosphatidylinositol phosphate biosynthetic process	1	481.5×	0.004	PIK3CG
regulation of angiogenesis	1	421.3×	0.005	PIK3CG
T cell proliferation	1	383.0×	0.005	PIK3CG
platelet aggregation	1	337.0×	0.005	PIK3CG
cellular response to cAMP	1	290.6×	0.006	PIK3CG
neutrophil chemotaxis	1	285.6×	0.006	PIK3CG
positive regulation of cytokine production	1	271.8×	0.006	PIK3CG
T cell activation	1	259.3×	0.006	PIK3CG
positive regulation of endothelial cell migration	1	251.5×	0.006	PIK3CG
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	PIK3CG
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.010	PIK3CG

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PIK3CG	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CG	56	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	PIK3CG
IDELALISIB	4	PIK3CG
ALPELISIB	4	PIK3CG
DUVELISIB	4	PIK3CG
COPANLISIB	4	PIK3CG
COPANLISIB HYDROCHLORIDE	4	PIK3CG
LENIOLISIB	4	PIK3CG
UMBRALISIB	4	PIK3CG
INAVOLISIB	4	PIK3CG
SUNITINIB	4	PIK3CG
DACTOLISIB	3	PIK3CG
BUPARLISIB	3	PIK3CG
TASELISIB	3	PIK3CG
QUERCETIN	3	PIK3CG
GEDATOLISIB	3	PIK3CG
LESTAURTINIB	3	PIK3CG
PF-04691502	2	PIK3CG
OMIPALISIB	2	PIK3CG
IZORLISIB	2	PIK3CG
APITOLISIB	2	PIK3CG
AZD-6482	2	PIK3CG
NEMIRALISIB	2	PIK3CG
DEZAPELISIB	2	PIK3CG
TG100-115	2	PIK3CG
VISTUSERTIB	2	PIK3CG
OSI-027	2	PIK3CG
BGT-226 FREE BASE	2	PIK3CG
PILARALISIB	2	PIK3CG
SAPANISERTIB	2	PIK3CG
VOXTALISIB	2	PIK3CG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PIK3CG	899	Binding:888, ADMET:8, Functional:2, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIK3CG	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PIK3CG	899

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	PIK3CG
IDELALISIB	4	PIK3CG
ALPELISIB	4	PIK3CG
DUVELISIB	4	PIK3CG
COPANLISIB	4	PIK3CG
COPANLISIB HYDROCHLORIDE	4	PIK3CG
LENIOLISIB	4	PIK3CG
UMBRALISIB	4	PIK3CG
INAVOLISIB	4	PIK3CG
SUNITINIB	4	PIK3CG
DACTOLISIB	3	PIK3CG
BUPARLISIB	3	PIK3CG
TASELISIB	3	PIK3CG
QUERCETIN	3	PIK3CG
GEDATOLISIB	3	PIK3CG
LESTAURTINIB	3	PIK3CG
PF-04691502	2	PIK3CG
OMIPALISIB	2	PIK3CG
IZORLISIB	2	PIK3CG
APITOLISIB	2	PIK3CG
AZD-6482	2	PIK3CG
NEMIRALISIB	2	PIK3CG
DEZAPELISIB	2	PIK3CG
TG100-115	2	PIK3CG
VISTUSERTIB	2	PIK3CG
OSI-027	2	PIK3CG
BGT-226 FREE BASE	2	PIK3CG
PILARALISIB	2	PIK3CG
SAPANISERTIB	2	PIK3CG
VOXTALISIB	2	PIK3CG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PIK3CG
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.