Extended Data Table 1. Description of monogenic diseases in this study.

Autoinflammatory Diseases
Disease Acronym	Gene/Protein	Disease Name	OMIM Number	Inheritance; Mutation effect	Phenotype	Pathomechanism of Inflammation	Ref
CAPS	NLRP3 / NLRP3	Familial cold autoinflammatory syndrome (FCAS): NLRP3-associated autoinflammatory disease-mild Muckle-Wells syndrome (MWS): NLRP3-associated autoinflammatory disease-moderate	120100, 191900	Autosomal Dominant / De novo; Gain of Function Mutations	Fever, urticaria-like rash, CNS inflammation, bone overgrowth	Constitutively active NLRP3 inflammasome and increased IL-1β production	(Aksentijevich and Schnappauf, 2021; Manthiram et al., 2017; Tangye et al., 2020)
DADA2	ADA2/CECR1 / ADA2	Deficiency of Adenosine Deaminase 2	615688	Autosomal Recessive; Loss of Function Mutations	Fever, lacunar strokes, livedo, immunodeficiency, anemia	Decrease in protein expression/activity leads to preferential differentiation of M1 proinflammatory macrophages,	(Aksentijevich and Schnappauf, 2021; Meyts and Aksentijevich, 2018)
FMF	MEFV / Pyrin	Familai Mediterranean Fever	249100	Autosomal Recessive; Gain of Function Mutations	Fever, serositis, rash, SAA amyloidosis	Facilitated activation of pyrin inflammasome leads to increased IL-1β production	(Aksentijevich and Schnappauf, 2021; Manthiram et al., 2017)
HIDS/MKD	MVK / MVK	Hyperimmunoglobulinemia D syndrome / Mevalonate Kinase Deficiency	260920, 610377	Autosomal Recessive; Loss of Function Mutations	Fever, serositis, rash, lymphadenopathy	Decrease in MVK activity enhances IL-1β production through activation of pyrin inflammasome	(Aksentijevich and Schnappauf, 2021; Manthiram et al., 2017)
PAPA	PSTPIP1 / PSTPIP1	Pyogenic Arthritis, Pyoderma Gangrenosum and Acne Syndrome	604416	Autosomal Dominant / De novo; Not known	Pyoderma, pyogenic arthritis, severe cystic acne	Increased affinity to pyrin causes enhanced IL-1β production	(Aksentijevich and Schnappauf, 2021; Manthiram et al., 2017; Tangye et al., 2020)
TRAPS	TNFRSF1A / TNFR1	TNFR1-associated Periodic Syndrome	142680	Autosomal Dominant / De novo; Not known	Fever, serositis, rash, myalgia, orbital inflammation, SAA amyloidosis	Misfolding of extracellular domain of the receptor leads to intracellular protein retention and increased endoplasmic reticulum (ER) stress	(Cudrici et al., 2020; Tangye et al., 2020)

Primary Immunodeficiency Diseases (see Tangye et al., 2020 for additional phenotypic and functional details and references)
Disease Acronym	Gene/Protein	Disease Name	OMIM Number	Inheritance; Mutation effect	Phenotype	Ref
STAT1 GOF	STAT1 / STAT1	STAT1-gain-of-function	614162	Autosomal Dominant / De novo; Gain of Function Mutations	Chronic mucocutaneous candidiasis, bacterial infections, viral infections, autoimmunity	(Tangye et al., 2020; Toubiana et al., 2016)
GATA2	GATA2 / GATA2	GATA2 deficiency / GATA2 haploinsufficiency	614172	Autosomal Dominant / De novo; Loss of Function Mutations	Lymphopenia, monocytopenia, myelodysplastic syndrome/acute myeloid leukemia, viral infections, NTM infection	(Spinner et al., 2014; Tangye et al., 2020)
APDS1	PIK3CD / p110δ catalytic subunit of PI3Kδ	Activated PI3K delta syndrome 1	615513	Autosomal Dominant / De novo; Gain of Function Mutations	Bacterial infection, lymphoproliferation, herpesvirus infections, autoimmunity	(Coulter et al., 2017; Tangye et al., 2020)
X-CGD	CYBB / p91phox	X-linked chronic granulomatous disease	306400	X-linked recessive; Loss of Function Mutations	Bacterial infection, invasive fungal infection, colitis, inflammatory lung disease, autoimmunity	(Arnold and Heimall, 2017; Henrickson et al., 2018; Tangye et al., 2020)
p47-CGD	NCF1 / p47phox	Autosomal recessive chronic granulomatous disease due to p47phox deficiency	233700	Autosomal Recessive; Loss of Function Mutations	Bacterial infection, invasive fungal infection, colitis, inflammatory lung disease, autoimmunity	(Arnold and Heimall, 2017; Henrickson et al., 2018; Tangye et al., 2020)
CTLA4	CTLA4 / CTLA4	CTLA4 haploinsufficiency	616100	Autosomal Dominant / De novo; Loss of Function Mutations	Hypogammaglobulinemia, lymphoproliferation, pulmonary infections, autoimmune cytopenias	(Schwab et al., 2018; Tangye et al., 2020)
PGM3	PGM3 / PGM3	PGM3 deficiency	615816	Autosomal Recessive; Loss of Function Mutations	Bacterial infections, atopic dermatitis, elevated serum IgE, skeletal abnormalities, developmental delay	(Bergerson and Freeman, 2019; Tangye et al., 2020)
LAD1	ITGB2 / integrin subunit β2	Leukocyte Adhesion Deficiency type 1	116920	Autosomal Recessive; Loss of Function Mutations	Periodontitis, skin infections, delayed umbilical cord separation	(Almarza Novoa et al., 2018; Tangye et al., 2020)
IL12R	IL12Rβ1 / IL12Rβ1	IL-12 receptor β1 deficiency	614891	Autosomal Recessive; Loss of Function Mutations	Invasive mycobacterial disease, chronic mucocutaneous candidiasis, Salmonella infection	(Bustamante et al., 2014; Tangye et al., 2020)
CARD14 DN	CARD14 / Caspase recruitment domain-containing protein 14	Dominant-negative CARD14 deficiency	607211	Autosomal Dominant / De novo; Dominant Negative Mutations	Severe atopic dermatitis, elevated serum IgE, food allergy, asthma	(Peled et al., 2019)
NEMO	IKBKG / inhibitor of nuclear factor kappa B kinase regulatory subunit gamma	NEMO deficiency	300636	X-linked recessive; Loss of Function Mutations	Ectodermal dysplasia, bacterial, viral, and mycobacterial infections, conical teeth, colitis	(Miot et al., 2017; Tangye et al., 2020)
STAT3 DN	STAT3 / STAT3	STAT3-dominant-negative hyper-IgE syndrome / autosomal dominant hyper-IgE syndrome / Job’s syndrome	147060	Autosomal Dominant / De novo; Dominant Negative Mutations	Bacterial infections, viral infections, atopic dermatitis, elevated serum IgE, skeletal and vascular abnormalities	(Bergerson and Freeman, 2019; Tangye et al., 2020)

Telomere disorders
Disease Acronym	Gene/Protein or RNA	Disease Name	OMIM Number	Inheritance; Mutation effect	Phenotype	Ref
TERT TERC	TERT / TERT protein TERC / TERC RNA molecule	Telomere biology disorder, or telomereopathy	614742, 614743	Autosomal Recessive; Loss of Function Mutations	Hypocellular and aplastic anemia, pulmonary fibrosis, liver disease	(Townsley et al., 2014)