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Table 3 Functional summary on genes sharing variants in at least two trios

From: Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Functional pathways Genes Description / Interaction Function Related diseases Add REF
Autophagy and trafficking Sec16A Endoplasmic Reticulum Export Factor ULK1, ULK2 (autophagy initiation) Familial axial spondyloarthritis [35, 36, 66]
AP5B1 Adaptator protein complex 5 AP membrane coat adaptor complex Atopic march and psoriasis [37, 67, 68]
RREB-1 Ras responsive element binding 1 RalA and RalB GTPases, DNA transcriptional regulator Unknown [49, 69,70,71]
ASPN Asporin (PLAP-1), ligand of CD44 Regulation of TLR2 and TLR4 in macrophages Osteoarthritis susceptibility [72,73,74,75]
RHBDL2 Rhomboid-like-2 serine protease Regulation of EGFR and anoikis resistance, angiogenesis Unknown [76,77,78]
RHBG Rhesus-associated (Rh) glycoproteins Ammonium transport in epithelial cells Unknown [79, 80]
KIR3DL1 killer cell immunoglobulin like receptor HLA interaction on NK and T-cells Psoriasis, spondyloarthritis, Behçet [81,82,83]
TDRD5 Tudor domain containing 5 Cytoplasmic RNA processing Spermatogenesis defects [84, 85]
MARCH10 Membrane-associated RING-CH 10 Microtubule-associated E3 ubiquitin ligase Unknown [86, 87]
AFAP1 Actin filament associated protein 1 Actin-binding protein and a cSrc-activating protein Unknown [88,89,90]
G-proteins regulation OBSCN Obscurin Rho-guanine nucleotide exchange factor Dilated cardiomyopathies [91, 92]
DNAH11 Dynein axonemal heavy chain 11 Component of the ciliary structure Primary ciliary dyskinesia [93,94,95]
CTNND2 δ-catenin/NPRAP/Neurojungin Regulation of Rho-GTPases in cytoskeleton Autism, complex human disordersa [47, 96]
CNGB1 (GARP) Cyclic nucleotide gated channel beta 1 cGMP signaling, guanylate cyclase, expressed on T-reg Retinitis pigmentosa [97,98,99,100]
ADGRV1 Adhesion G protein-coupled receptor V1 G-protein coupled receptor binding calcium Usher syndrome type IIb [101, 102]
NPHS2 Podocin (specific for podocytes) Filtration barrier in mammalian kidney (TRPC channel) Nephrotic syndromes [103,104,105]
T-cell activation IDO2 Indoleamine 2,3-dioxygenase 2 Acts for IDO1 dependent induction of T-regulatory cells Colitis, arthritis [52, 53, 106]
IGSF3 (EWI-3) Immunoglobulin superfamily member 3 Putative interaction with CD9 and CD81 (TPSPAN) Unknown [107,108,109,110]
PIEZO1 Piezo type mechanosensitive ion channel 1 Mechanotransduction and regulation of cell morphology Hereditary Xerocytosis [111,112,113]
HSD17B4 Hydroxysteroid 17-beta dehydrogenase 4 Beta-oxidation of very long chain fatty acids PERRAULT syndromec [114, 115]
Cell cycle - immune synapse SPICE1 Spindle and centriole associated protein 1 Regulation of centrioles elongation with CEP120 and CPAP Unknown [61, 116]
KNL1 (CASC5) Kinetochore scaffold 1 Stabilization of sister chromatids to microtubules Unknown [64, 117,118,119]
CCT6B Chaperonin containing TCP1 subunit 6B Transcriptional response to stress in mitotic cells Unknown [120, 121]
PCNT Pericentrin, phosphorylated by PLK1 Ensure proper centrosome and mitotic spindle formation Primordial dwarfism [122,123,124]
PCDHB16 Protocadherin beta 16 Cell-cell adhesion and intracellular signalling Unknown [125, 126]
CMYA5 (TRIM76) Cardiomyopathy associated 5, myospryn Muscle target gene for the MEF2A transcription factor Hypertrophic cardiomyopathyd,e [127,128,129,130]
Innate immunity CPAMD8 Alpha-2-macroglobulin domain containing 8 Up-regulated in immune stimulated cells Anterior segment dysgenesis [131, 132]
WFDC3 (WAP14) WAP four-disulfide core domain 3 Antimicrobial, immune, and tissue homoeostasis activities Unknown [133, 134]
FCGBP Fc fragment of IgG binding protein Regulator of TGF-1-induced EMf transition Unknown [135, 136]
  1. Unclassified: OR11G2, PRSS48, ZNF804A, ZNF717, TYR, SLC16A8, PRSS55, AIM1L
  2. Abbreviations of each gene name are detailed in the text
  3. athe CTNND2 gene has been linked to a broad spectrum of human diseases, such as cancer, bipolar disorder, schizophrenia, autism, Cri-du-chat syndrome, myopia, cortical cataract-linked Alzheimer’s disease, and infectious diseases. bGlycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats (LRR), has been found to be highly expressed on the surface of activated T-reg cells. cPatients with Usher syndrome type 2 present hearing loss and develop a visual impairment called Retinitis pigmentosa, a disease not observed in our cases, the c.6695A > G variant described in T1 + T2 being not described in this syndrome. dPERRAULT syndrome is a rare recessive disease characterized by hearing loss, ovarian dysgenesis, intellectual disability and ataxia, a condition which is not observed in our cases, the c.1606 T > C (T2) and c.392G > A (T3) variants being not linked to this rare disease. ethe clinical screening of T1 and T2 affected children did not identify hypertrophic cardiomyopathy. fEM: epithelial to mesenchymal transition