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20 Feb 2021

The study of rare immune disorders.

Note: in genomic analysis cohort studies a purely statistical approach is preferrable to prevent bias in the initial discovery phase. The following pertains to rare disease or single case studies where traditional statistical based assocciations are impossible detect. A link to new statistical based approaches for rare disease will also be provided shortly.

Our goal is the discovery of rare variants in primary immune deficiency diseases and autoinflammatory disease. There is a long history of advancements in the field of immunology by investigating rare diseases. In a very broad sense immunology can be approached in two ways;

  1. Categorically define each protein and signalling mechanism in a pathway or
  2. Identify monogenic or complex genetic causes for immune disorders to identify new or known protein functions.

Both of these approaches require a priori knowledge; i.e. “what functional experiment will demonstrate the mechanism of the system or protein of interest, and how does a genetic variant explain the phenotype demonstrated by a patient” The second method is discussed carefully by Casanova and Notarangelo.

Novel discovery of rare mutations in immune genes has some hurdles.

  • The patients included for sequencing must be selected carefully. The majority of disease-causing mutations identified will be known variants, those that are obviously damaging, etc. and have defined treatments. These must be identified quickly to focus on more significant discoveries.
  • Novel discoveries require functional experimentation to prove mechanism. This can require a major investment for complex studies and therefore ends up itself taking investigation approach number 1 mentioned above.

There are two options for the approach:

  • Small single-case studies that require some functional work along with clinical investigation.
    • This first option can have very dramatic consequences for understanding protein function - when the phenotype is extremely strong it is easier to identify.
  • Cohort studies on larger groups of affected patients where the phenotype is not as profound as rare single cases disorders.
    • This second option is more statistically reliable but the effect sizes tend to be much smaller. Sample sizes are usually also small for rare diseases.

Genomic analysis protocol

The best-practice methods for genomic analysis are discussed in other posts including “Genomic analysis for rare disease”. These methods are generally a routine protocol that is performed for every sample, and dependant on the technology used; i.e. genome sequencing with illumina short reads, 10x Genomics long reads, RNAseq, Hi-C, etc.

The disease-specific subtleties still often require a highly tailored analysis protocol to correctly identify a genetic determinant of disease. A simple explanation is seen with disease genes where knowledge about protein function is used for annotation of candidate disease variants

Immune disorder genes

The genes which are most often identified in immune disorders can be separated into those of Primary Immunodeficiency (PID) and Autoinflammatory diseases. Of course there is overlap as many proteins have multiple functions (inhibitory, activation, autoinhibition, etc.). The analysis protcols use several stages of best-practice clinical genetic annotations accounting for numerous diagnosis criteria including variant consequence, gene ontology, inheritance, protein domain function, transcription editing, translation modification, etc. A reliable example of a disease gene list can be found on the Genomics England panel app Primary immunodeficiency.

The (simplified) list that I try to keep updated and close to hand when doing tailored bioinformatic analysis is exemplified in the following table. The analysis pipeline uses a curated and reliable sources to provide a data-rich annotation process for candidate variant detection. However, as a repository of whole genome annotation, the information is difficult to illustrate here in a small image. Instead, the included table is a very simplified example of candidate genes in immunogenomics. Note that candidate gene approaches are not recommended, this list is an example of known functions that are applied to results after unbiased significance testing.

Primary Immunodeficiency (PID) genes

PID genes Disorder inheritance
ACP5 Spondyloenchondrodysplasia with immune dysregulation AR
ACTB Baraitser-Winter syndrome 1  
ADA Adenosine deaminase (ADA) deficiency AR
ADAR Aicardi-Goutieres syndrome 6  
AICDA Immunodeficiency with hyper-IgM, type 2 AR
AIRE Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia (APECED) AR
AK2 Reticular dysgenesis, AK2 deficiency AR
AP3B1 Hermansky-Pudlak syndrome 2 AR
APOL1 Trypanosomiasis, susceptibility to  
ARVCF DiGeorge syndrome  
ATM Ataxia-telangiectasia AR
BCL10 combined immunodeficiency with B cell, T cell, and fibroblast defects  
BLM Bloom syndrome AR
BLNK Agammaglobulinemia 4 AR
BTK Agammaglobulinemia, X-linked 1 (XLA) x-linked
C1QA C1q deficiency AR
C1QB C1q deficiency AR
C1QC C1q deficiency AR
C1R C1r/C1s deficiency, combined AR
C1S C1s deficiency AR
C2 C2 deficiency AR
C3 C3 deficiency AD
C4A C4a deficiency AR
C4B C4B deficiency AR
C5 C5 deficiency  
C6 C6 deficiency AR
C7 C7 deficiency  
C8A C8 deficiency, type I AR
C8B C8 deficiency, type II AR
C8G Complement factor 8 defect AR
C9 C9 deficiency AR
CA2 Osteopetrosis, autosomal recessive 3, with renal tubular acidosis  
CARD11 Immunodeficiency 11/ CARD11 deficiency; Persistent polyclonal B-cell lymphocytosis AR
CARD14 Pityriasis rubra pilaris  
CARD9 Candidiasis, familial, 2, autosomal recessive AR
CASP10 Autoimmune lymphoproliferative syndrome, type II AD
CASP8 Immunodeficiency due to CASP8 deficiency AD
CCBE1 Hennekam lymphangiectasia-lymphedema syndrome 1  
CD19 Immunodeficiency, common variable, 3 AR
CD247 Immunodeficiency 25 AR
CD27 Lymphoproliferative syndrome 2 AR
CD28 combined immunodeficiency T cell  
CD3D CD3d deficiency AR
CD3E CD3e deficiency AR
CD3G CD3g deficiency AR
CD4 OKT4 epitope deficiency  
CD40 CD40 deficiency AR
CD40LG CD40 ligand deficiency x-linked
CD46 Hemolytic uremic syndrome, atypical, susceptibility to, 2  
CD55 Hemolysis syndrome  
CD59 Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy  
CD79A Agammaglobulinemia 3 AR
CD79B Agammaglobulinemia 6 AR
CD81 Immunodeficiency, common variable, 6 AR
CD8A CD8 deficiency AR
CDKN2A Neutropenia, severe congenital  
CEBPE Specific granule deficiency AR
CECR1 ADA2 deficiency AR
CFB Complement factor B deficiency AR
CFD Complement factor D deficiency AR
CFH Complement factor H deficiency AR and AD
CFHR1 Hemolytic uremic syndrome, atypical, susceptibility to  
CFHR3 Hemolytic uremic syndrome, atypical, susceptibility to  
CFI Complement factor I deficiency AR
CFP Properdin deficiency, X-linked x-linked
CHD7 Charge syndrome AD
CIITA Bare lymphocyte syndrome, type II, complementation group A AR
CLCN7 Osteopetrosis, autosomal recessive  
CLEC7A Candidiasis, familial, 4, autosomal recessive AR
CNBP Myotonic dystrophy 2  
COLEC11 3MC syndrome 2  
COMT DiGeorge syndrome AD
CORO1A Coronin-1A deficiency AR
CR2 Immunodeficiency, common variable, 7  
CSF2RA Surfactant metabolism dysfunction, pulmonary, 4  
CSF3R Severe congenital neutropenia AD
CTLA4 Common variable immunodeficiency - Autosomal dominant immune dysregulation syndrome AD
CTPS1 Immunodeficiency 24 AR
CTSC Papillon-Lefevre syndrome  
CXCR4 WHIM syndrome AD
CYBA Chronic granulomatous disease, autosomal, due to deficiency of CYBA AR
CYBB Chronic granulomatous disease, X-linked x-linked
DCLRE1B Hoyeraal-Hreidarsson syndrome  
DCLRE1C DCLRE1C (Artemis) deficiency AR
DKC1 Dyskeratosis congenita, X-linked x-linked
DNASE1 Systemic lupus erythematosus AD
DNMT3B Immunodeficiency-centromeric instability-facial anomalies syndrome 1 AR
DOCK8 Hyper-IgE recurrent infection syndrome, autosomal recessive AR
ELANE Neutropenia, severe congenital 1, autosomal dominant AD
ELF4 undetermined  
F12 Angioedema, Hereditary, Type III AD
FADD Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations  
FAS Autoimmune lymphoproliferative syndrome, type IA (ALPS-FAS) AD
FASLG Autoimmune lymphoproliferative syndrome, type IB (ALPS-FASG) AD
FCGR1A IgG receptor I, phagocytic, familial deficiency of  
FCGR2A Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis  
FCGR2B Malaria, resistance to  
FCGR3A Immunodeficiency 20 AR
FCGR3B Neutropenia, alloimmune neonatal  
FCGRT none reported  
FCN3 Immunodeficiency due to ficolin 3 deficiency  
FERMT3 Leukocyte adhesion deficiency, type III AR
FOXN1 T-cell immunodeficiency, congenital alopecia, and nail dystrophy AR
FOXP3 Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) x-linked
FPR1 Periodontitis  
G6PC3 Neutropenia, severe congenital 4, autosomal recessive AR
G6PD Chronic Granulomatous Disease x-linked
GATA2 Immunodeficiency 21 AD
GFI1 Neutropenia, severe congenital 2, autosomal dominant AD
GP1BB DiGeorge syndrome/Bernard Soulier syndrome  
HAX1 Neutropenia, severe congenital 3, autosomal recessive AR
HIRA DiGeorge syndrome AD
ICOS Immunodeficiency, common variable, 1 AR
IFIH1 Aicardi-Goutieres syndrome 7  
IFNGR1 Immunodeficiency 27A, mycobacteriosis, AR; Immunodeficiency 27B, mycobacteriosis, AD AD
IFNGR2 Immunodeficiency 28, mycobacteriosis AR
IGAD1 Immunoglobulin A deficiency AR and AD
IGHM Agammaglobulinemia 1 AR
IGKC Kappa light chain deficiency AR
IGLL1 Agammaglobulinemia 2 AR
IKBKB Immunodeficiency 15 AR
IKBKG Ectodermal dysplasia, hypohidrotic, with immune deficiency; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency; Immunodeficiency 33; Immunodeficiency, isolated; Invasive pneumococcal disease, recurrent isolated, 2 X-Linked
IKZF1 Leukemia, acute lymphoblastic AR
IL10 Early onset inflammatory bowel disease AR
IL10RA Inflammatory bowel disease 28, early onset, autosomal recessive AR
IL10RB Inflammatory bowel disease 25, early onset, autosomal recessive AR
IL12B Immunodeficiency 29, mycobacteriosis AR
IL12RB1 Immunodeficiency 30 AR
IL12RB2 Mendelian susceptibility to mycobacterial disease AR
IL17F Candidiasis, familial, 6, autosomal dominant AD
IL17RA Candidiasis, familial, 5, autosomal recessive AR
IL17RC Chronic Mucocutaneous Candidiasis (CMC) AR
IL18 Defects with susceptibility to mycobacterial infection (MSMD)  
IL1RN Interleukin 1 receptor antagonist deficiency  
IL21 Immunodeficiency, common variable, 11 AR
IL21R Immunodeficiency, primary, autosomal recessive, IL21R-related AR
IL23A Defects with susceptibility to mycobacterial infection (MSMD)  
IL2RA Interleukin-2 receptor, alpha chain, deficiency of AR
IL2RG SCID (x-linked) X-Linked
IL36RN Psoriasis, generalized pustular AR
IL7R IL7Ra deficiency AR
IRAK4 IRAK4 deficiency AR
IRF3 susceptibility to herpes simplex encephalitis  
IRF7 IRF7 deficiency  
IRF8 Immunodeficiency 32A, mycobacteriosis, autosomal dominant AR and AD
ISG15 susceptibility to mycobacterial infection, enhanced IFN-?/? immunity AR
ITCH Autoimmune disease, multisystem, with facial dysmorphism AR
ITGB2 Leukocyte adhesion deficiency AR
ITK Lymphoproliferative syndrome 1 (LPFS1) AR
JAGN1 severe congeital neutropenia AR
JAK3 JAK3 deficiency AR
KRAS Ras associated lymphoproliferative disease (RALD) AR and somatic
LAMTOR2 Immunodeficiency due to defect in MAPBP-interacting protein AR
LCK Immunodeficiency 22/ LCK deficiency AR
LIG1 DNA ligase I deficiency AR
LIG4 LIG4 syndrome AR
LPIN2 Majeed syndrome AR
LRBA Immunodeficiency, common variable, 8, with autoimmunity AR
LRRC8A Agammaglobulinemia 5 AD
LYST Chediak-Higashi syndrome AR
MAGT1 Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) X-Linked
MALT1 Immunodeficiency 12/ MALT1 deficiency AR
MASP1 3MC syndrome 1 AR
MASP2 MASP2 deficiency AR
MBL2 Chronic infections, due to MBL deficiency AR/het
MCM4 Natural killer cell and glucocorticoid deficiency with DNA repair defect AR
MEFV Familial Mediterranean fever, AR; Familial Mediterranean fever, AD AR
MKL1 immunodeficiency, phagocyte function AR
MLPH Griscelli syndrome, type 3 AR
MPO Myeloperoxidase deficiency AR/het
MRE11A Ataxia-telangiectasia-like disorder AR
MS4A1 Immunodeficiency, common variable, 5 AR
MTHFD1 Severe combined immunodeficiency, defect in folate metabolism  
MVK Hyper-IgD syndrome AR
MYD88 Pyogenic bacterial infections, recurrent, due to MYD88 deficiency AR
MYO5A Griscelli syndrome, type 1 AR
NBN Nijmegen breakage syndrome AR
NCF1 Chronic granulomatous disease due to deficiency of NCF-1 AR
NCF2 Chronic granulomatous disease due to deficiency of NCF-2 AR
NCF4 Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III AR
NFKB1 Common variable immunodeficiency (CVID)  
NFKB2 Immunodeficiency, common variable, 10 AD
NFKBIA Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency AD
NHEJ1 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation AR
NHP2 Dyskeratosis congenita, autosomal recessive 2 AR
NLRP12 Familial cold autoinflammatory syndrome 2 het
NLRP3 CINCA syndrome; Muckle-Wells syndrome AR
NOD2 Blau syndrome  
NOP10 Dyskeratosis congenita, autosomal recessive 1 AR
NRAS Autoimmune lymphoproliferative syndrome type IV  
ORAI1 Immunodeficiency 9 AR
OSTM1 Osteopetrosis, autosomal recessive 5  
PGM3 Immunodeficiency 23 AR
PIK3CD Immunodeficiency 14 AD
PIK3R1 Agammaglobulinemia 7, autosomal recessive AR
PLCG2 Autoinflammation, antibody deficiency, and immune dysregulation syndrome AD
PMS2 Mismatch repair cancer syndrome  
PNP Immunodeficiency due to purine nucleoside phosphorylase deficiency; Purine nucleoside phosphorylase (PNP) deficiency AR
POLE FILS syndrome AR
PRF1 Hemophagocytic lymphohistiocytosis, familial, 2 AR
PRKCD Immunodeficiency, common variable, 9; ALPS3 AR
PRKDC DNA Pkcs deficiency AR
PSMB8 Autoinflammation, lipodystrophy, and dermatosis syndrome AR
PSTPIP1 Pyogenic sterile arthritis, pyoderma gangrenosum, and acne  
PTPRC CD45 deficiency AR
RAB27A Griscelli syndrome, type 2 AR
RAC2 Neutrophil immunodeficiency syndrome  
RAG1 RAG1 deficiency AR
RAG2 RAG2 deficiency AR
RBCK1 Polyglucosan body myopathy, early-onset, with or without immunodeficiency AR
RECQL4 Rothmund-Thomson syndrome AR
RFX5 Bare lymphocyte syndrome, type II, complementation group C AR
RFXANK MHC class II deficiency, complementation group B AR
RFXAP Bare lymphocyte syndrome, type II, complementation group D AR
RHOH RhoH deficiency AR
RMRP Cartilage-hair hypoplasia AR
RNASEH2A Aicardi-Goutieres syndrome 4  
RNASEH2B Aicardi-Goutieres syndrome 2  
RNASEH2C Aicardi-Goutieres syndrome 3  
RNF168 RIDDLE syndrome AR
RORC Susceptibility to candidasis & Mycobacterial infection  
RPSA Isolated congential asplenia AR
RTEL1 Hoyeraal-Hreidarsson syndrome/ Dyskeratosis congenita, autosomal dominant 4; Dyskeratosis congenita, autosomal recessive 5 AR and AD
SAMHD1 Aicardi-Goutieres syndrome 5  
SBDS Shwachman-Bodian-Diamond syndrome AR
SEMA3E Charge syndrome AD
SERPING1 Angioedema, hereditary, types I and II AD
SH2D1A Lymphoproliferative syndrome, X-linked, 1 (XLP1) X-Linked
SH3BP2 Cherubism  
SLC11A1 Mycobacterium tuberculosis, susceptibility to infection by  
SLC29A3 Histiocytosis-lymphadenopathy plus syndrome AR
SLC35C1 Congenital disorder of glycosylation, type IIc AR
SLC37A4 Glycogen storage disease Ib  
SLC46A1 Folate malabsorption, hereditary  
SMARCAL1 Schimke immunoosseous dysplasia AR
SP110 Hepatic venoocclusive disease with immunodeficiency AR
SPINK5 Netherton syndrome AR
STAT1 Immunodeficiency 31A, mycobacteriosis, autosomal dominant; Candidiasis, familial, 7 AR and AD
STAT2 STAT2 deficiency AR
STAT3 Hyper-IgE recurrent infection syndrome; Autoimmune disease, multisystem, infantile-onset AR/AD
STAT5A Growth hormone insensitivity with immunodeficiency  
STAT5B Growth hormone insensitivity with immunodeficiency AR
STIM1 Immunodeficiency 10 AR
STK4 T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations AR
STX11 Hemophagocytic lymphohistiocytosis, familial, 4 AR
STXBP2 Hemophagocytic lymphohistiocytosis, familial, 5 AR
TAP1 Bare lymphocyte syndrome, type I AR
TAP2 Bare lymphocyte syndrome, type I, due to TAP2 deficiency AR
TAPBP Bare lymphocyte syndrome, type I AR
TAZ Barth syndrome X-Linked
TBK1 Herpes simplex encephalitis, susceptibility to,  
TBX1 Di George syndrome AD
TCF3 E47 TF deficiency  
TCIRG1 Osteopetrosis, autosomal recessive 1  
TCN2 Transcobalamin-2 precursor AR
TERC Dyskeratosis congenita, autosomal dominant 1 AD
TERT Dyskeratosis congenita, autosomal dominant 2, Dyskeratosis congenita, autosomal recessive 4 AD
THBD Hemolytic uremic syndrome, atypical, susceptibility to, 6  
TICAM1 Encephalopathy, acute, infection-induced, susceptibility to, 6 AR and AD
TINF2 Dyskeratosis congenita, autosomal dominant 3 AD
TIRAP Pneumococcal disease, invasive, protection against  
TLR3 Herpes simplex encephalitis, susceptibility to, 2  
TMC6 Epidermodysplasia verruciformis  
TMC8 Epidermodysplasia verruciformis  
TMEM173 STING-associated vasculopathy, infantile-onset  
TNFRSF11A Osteolysis, familial expansile ; Osteopetrosis, autosomal recessive 7  
TNFRSF13B Immunodeficiency, common variable, 2 AR and AD
TNFRSF13C Immunodeficiency, common variable, 4 AR
TNFRSF1A Periodic fever, familial AD
TNFRSF4 Immunodeficiency 16/ OX40 deficiency AR
TNFSF12 Immunodeficiency, common variable with lack of anti-pneumococcal antibody  
TPP2 TPP2 deficiency  
TRAC Immunodeficiency 7, TCR-alpha/beta deficient AR
TRAF3 Herpes simplex encephalitis, susceptibility to, 3 AD
TRAF3IP2 Candidiasis, familial, 8 AR
TREX1 Aicardi-Goutieres syndrome 1, dominant and recessive  
TRNT1 congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) AR
TTC37 Trichohepatoenteric syndrome 1  
TTC7A Multiple intestinal atresia and severe combined immunodeficiency (MINAT) AR
TYK2 Immunodeficiency 35 AR
UFD1L DiGeorge syndrome AD
UNC119 Immunodeficiency 13/ UNC119 deficiency  
UNC13D Hemophagocytic lymphohistiocytosis, familial, 3 AR
UNC93B1 Herpes simplex encephalitis, susceptibility to, 1 AR
UNG Immunodeficiency with hyper IgM, type 5 AR
USB1 Poikiloderma with neutropenia AR
VPS13B Cohen syndrome AR
VPS45 Neutropenia, severe congenital, 5, autosomal recessive AR
WAS Wiskott-Aldrich syndrome X-Linked
WIPF1 Wiskott-Aldrich syndrome 2 AR
WRAP53 Dyskeratosis congenita, autosomal recessive 3 AR
XIAP Lymphoproliferative syndrome, X-linked, 2 (XLP2) X-Linked
XRCC4 none reported  
ZAP70 Zap-70 deficiency AR
ZBTB24 Immunodeficiency-centromeric instability-facial anomalies syndrome-2 AR

Autoinflammatory disease genes

Autoinflammatory genes Disorder
ACP5 Spondyloenchondrodysplasi a with immune dysregulation
ACP5 Spondyloenchondrodysplasia with immune dysregulation
ADAR Dyschromatosis symmetrica hereditaria, Aicardi-Goutières syndrome
Aicardi  Goutieres syndromes (AGS) TREX1 (AGS1), RNASEH2B (AGS2), RNASEH2C (AGS3), RNASEH2A (AGS4), SAMHD1 (AGS5), ADAR (AGS6), and IFIH1 (AGS7)
AP1S3 Pustular psoriasis (PSORS15)
CARD14 Familial Psoriasis (PSORS2)
CECR1 Deficiency of Adenosine Deaminase 2 (DADA2) aka Fever with Early Onset Stroke (FEOS)
DDX58 Singleton-Merten syndrome
ELANE Cyclic Neutropenia
FOXP3 IPEX syndrome
GCH1 Dopa responsive dystonia, Tetrahydrobiopterin deficiency
Gene Associated phenotypes
HAX1 Severe Congenital Neutropenia
HTR1A Periodic fever, menstrual cycle
IFIH1 Singleton-Merten syndrome
IL10 Early Onset Inflammatory Bowel Disease (EoIBD25, EOIBD28, and EOIBD with Il10 deficiency)
IL10RA Early Onset Inflammatory Bowel Disease (EoIBD25, EOIBD28, and EOIBD with Il10 deficiency)
IL10RB Early Onset Inflammatory Bowel Disease (EoIBD25, EOIBD28, and EOIBD with Il10 deficiency)
IL1RN Deficiency of Interleukin 1ß (IL1ß) Receptor Antagonist (DIRA) . Osteomyelitis, sterile multifocal, with periostitis and pustulosis
IL36RN Pustular psoriasis, generalized  - Deficiency of Interleukin 36Receptor Antagonist (DITRA)
ISG15 Immunodeficiency 38 with basal ganglia calcification (IMD38)
LPIN2 Majeed syndrome
MEFV Familial Mediterranean Fever (FMF)
MVK Mevalonate Kinase Deficiencies (MKD): Hyper-IgD syndrome (HIDS) and MA
NEFL Charcot Marie
NLRC4 NLRC4 Macrophage Activation
NLRP12 Familial Cold Autoinflammatory Syndrome 2 (FCAS2)
NLRP3 Cryopyrin Associated Periodic Syndromes (CAPS): MWS, FCAS, CINCA and NOMID
NLRP7 Recurrent hydatidiform mole
NOD2 Blau syndrome, Sarcoidosis, early-onset
ORAI1 Myopathy, tubular aggregate, 2 (TAM2), Immunodeficiency 9 (IMD9)
PLCG2 PLCG2associated Antibody Deficiency & Immune Dysregulation (PLAID) or Familial Atypical Cold Urticaria (FACU) or FCAS3 and APLAID
PSMB8 Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome (CANDLE), Nakajo-Nishimura syndrome, Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, Autoinflammation, lipodystrophy, and dermatosis syndrome, Joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome
PSTPIP1 Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA)
RBCK1 Polyglucosan body myopathy 1 with or without immunodeficiency (PGBM1)
RNASEH2A Aicardi-Goutières syndrome
RNASEH2B Aicardi-Goutières syndrome
RNASEH2C Aicardi-Goutières syndrome
SAMHD1 Aicardi-Goutières syndrome
SCO2 Myopia 6 (MYP6), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (CEMCOX1)
SH3BP2 Cherubism
SLC19A3 biotin thiamine responsive basal ganglia disease
SLC25A19 Amish lethal microcephaly
SLC29A3 SLC29A3 Spectrum Disorder, aka H. syndrome; Pigmented Hypertrichosis with Insulin dependent Diabetes Mellitus (IDDM)
TLR3 Human immunodeficiency virus type 1, susceptibility to
TMEM173 STING-associated vasculopathy, infantile-onsent (SAVI)
TNFAIP3 Haploinsufficiency of A20 (HA20), aka Behcet
TNFRSF11A TNFRSF11A associated hereditary fever disease (TRAPS11)
TNFRSF1A Periodic fever (Tumor Necrosis Factor (TNF) Associated Periodic Syndrome (TRAPS))
TPK1 Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5)
TRAF3 Herpes simplex encephalitis, susceptibility to
TREX1 Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndrome
TRNT1 Sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay (SIFD)