Disease	Gene	Clinical findings
STAT-1 GOF	STAT-1	• Chronic mucocutaneous candidiasis • Recurrent respiratory infections • Organ specific autoimmunity • Combined immune deficiency
STAT-3 GOF: early-onset lymphoproli-feration with multiorgan autoimmunity	STAT-3	• Early-onset recurrent infections • Lymphadenopathy • Hepatosplenomegaly • Autoimmune disorders (hemolytic anemia, thrombocytopenia, neutropenia, enteropathy, type I diabetes, scleroderma, arthritis, atopic dermatitis, and inflammatory lung disease) • Failure to thrive • Decreased regulatory T cells • Hypogammaglobulinemia • Low memory B cells
APDS1 and APDS2 (activated phosphoinositide 3-kinase syndrome)	PIK3CD (GOF) PIK3R1 (LOF)	• Lymphoproliferation • Recurrent sinopulmonary infections • Airway damage • Chronic herpesvirus viremia • ± elevated IgM
CTLA-4 deficiency	CTLA-4	• Autoimmune cytopenias • Lymphoproliferation • Hypogammaglobulinemia • Lymphocytic infiltration of non-lymphoid organs • Increased risk of lymphoma
LRBA deficiency	LRBA	• Lymphoproliferation • Autoimmunity • Hypogammaglobulinemia • Recurrent infections • Increased risk of lymphoma
CVID (common variable immune deficiency)	Multifactorial	• Hypogammaglobulinemia, low IgA or M • Poor response to vaccines • Low memory B cells • Recurrent sinopulmonary infections, bronchiectasis • Autoimmunity
HIGM (hyper-IgM syndrome)
	CD40L CD40	• Recurrent sinopulmonary infections • Susceptibility to opportunistic infections • Neutropenia • Autoimmunity
	AID UNG	• Recurrent sinopulmonary infections • Gastrointestinal infections (Giardia or viruses) • Splenomegaly • Lymphadenopathy • Autoimmune cytopenia • Hepatitis • Inflammatory bowel syndrome • Arthritis
SCID (severe combined immune deficiency)		• Severe recurrent infections • Failure to thrive • Thrush • Diarrhea
	IL2-Rγc-chain JAK3	• T-B + NK-
	IL7Rα def	• T-B + NK +
	RAG1/2	• T-B-NK +
	ADA	• T-B-NK- • Deficiency of adenosine deaminase is toxic to lymphocytes • Neurodevelopmental deficits • Sensorineural deafness • Skeletal abnormalities • Hepatic abnormalities
HLH (hemophagocytic lympho-histiocytosis)	Familial: 1: chromsm-9 2: PRF1 3: UNC13D 4: STX11 5: STXBP2 X-linked (XLP): SH2D1A XIAP	• Fever • Hepatomegaly/splenomegaly • Rash • Lymphadenopathy • Thrombocytopenia • Kidney abnormalities • Cardiac • Increased risk for certain cancers
GATA2 deficiency	GATA2	• Monocytopenia and Mycobacterial infection syndrome: dendritic cell, monocyte, B and NK lymphoid deficiency • Familial myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) • Emberger syndrome: deafness-lymphedema-leukemia syndrome • NK cell deficiency • Variable symptoms:  o Severe infections (viral or nontuberculous mycobacterial infections)  o Respiratory problems  o Hearing loss  o Lymphedema  o Myelodysplasia, acute myeloid leukemia, or chronic myelomonocytic leukemia
CGD (chronic granulomatous disease), (defects in genes for subunits of NADPH oxidase)	CYBA CYBB NCF1 NCF2 NCF4	• Indolent bacterial and fungal infections • Granulomas of the gastrointestinal tract and the genitourinary system • Abscesses of lungs, liver, spleen, bones, or skin • Lymphadenopathy • Diarrhea • [CYBB form is x-linked, others are AR recessive]
CTPS1 deficiency (rare type of SCID)	CTPS1	• Early-onset, severe viral infections with EBV and VZV • Recurrent sinopulmonary bacterial infections • Defective T and B cell proliferation
WAS (Wiskott Aldrich syndrome)	WAS	• Thrombocytopenia, bleeding • Eczema • Combined immunodeficiency • opportunistic infections • Autoimmunity: autoimmune hemolytic anemia, neutropenia, vasculitis, inflammatory bowel disease, renal disease, and arthritis • High risk of B cell lymphomas
NK cell deficiencies	FCGR3A	• Recurrent infections, (herpes, papillomavirus) • Lymphoproliferation • Decreased or normal NK cell number • Defective NK function in spontaneous cellular cytotoxicity • Antibody-dependent cellular cytotoxicity unaffected
	GATA-binding protein 2 gene	• Pulmonary alveolar proteinosis • Aplastic anemia • Recurrent infections (viruses and fungi, mycobacteria) • Cytopenia: monocytes, dendritic cells, neutrophils, and B cells • Decreased NK cells and NK cell precursors • Deficient NK cell-mediated and antibody-mediated cytotoxicity • Susceptibility to myelodysplasia and myeloid leukemia