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Atlas / Disease / selective IgA deficiency disease

selective IgA deficiency disease

disease
On this page

Also known as deficiencies, IgAdeficiency, IgAIgA deficienciesimmunoglobulin A deficiencyselective IgA immunodeficiencySIgAD

Summary

selective IgA deficiency disease (MONDO:0001341) is a disease with 38 cohort genes (33 GWAS associations across 1 studies).

At a glance

  • Cohort genes: 38
  • GWAS associations: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameselective IgA deficiency disease
Mondo IDMONDO:0001341
EFOEFO:1001929
MeSHD017098
Orphanet69127
DOIDDOID:0060025, DOID:11701
NCITC26964
SNOMED CT29260007
UMLSC4049006
MedGen883982
GARD0027574
Is cancer (heuristic)no

Also known as: deficiencies, IgA · deficiency, IgA · IgA deficiencies · immunoglobulin A deficiency · selective IgA immunodeficiency · SIgAD

Data availability: 33 GWAS associations (1 study).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › selective immunoglobulin deficiency disease › dysgammaglobulinemia › selective IgA deficiency disease

Related subtypes (3): selective IgE deficiency disease, selective IgM deficiency, selective IgG immunodeficiency

Subtypes (3): IgAD1, secretory component deficiency, immunoglobulin A deficiency 2

Genetics & variants

GWAS landscape

33 GWAS associations across 1 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1160417863e-92HLA-DQA1T2.63
rs19907604e-15IFIH1T1.43
rs112996004e-11PVT1 - RN7SKP226T0.73
rs45658707e-10CREB3L1 - DGKZC1.38
rs77739878e-10AHI1T0.7
rs340693911e-09CLEC16AG1.41
rs12441815e-08GATA3-AS1, GATA3G1.37
rs122570927e-08FAST1.27
rs672579592e-07CPAMD8 - HAUS8C1.25
rs98318942e-07CD86C1.26
rs168627803e-07LINC01991A1.33
rs801685063e-07LINC01953 - SPAG16-DTG0.64
rs100717615e-07RNU1-150P - TTC33C1.25
rs80717897e-07IKZF3T1.23
rs21366137e-07EGR2 - RNU6-543PT0.8
rs22109139e-07FCRL3T1.23
rs109058751e-06RBM17 - PFKFB3C1.34
rs129676781e-06PTPN2A1.38
rs1465837071e-06IL2 - IL21A1.25
rs47460912e-06CDH23C0.78
rs168957682e-06MAST4C0.77
rs561460073e-06FOXP1G1.22
rs122494673e-06PRKG1A1.33
rs76662863e-06RNU1-45P - RNA5SP173A1.8
rs107335473e-06DMRT1C0.77
rs3919364e-06LINC00299G1.2
rs96094524e-06AP1B1P1 - C22orf42T1.42
rs122579615e-06FAM171A1A1.22
rs22513815e-06MAP3K7CLG1.21
rs1126121167e-06PPIF - ZCCHC24A0.56

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST003814Bronson PG20161,6354,852Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic32

MAF distribution

BucketVariants
common (>=0.05)32
low_freq (0.01-0.05)0
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant21
intergenic_variant11
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1160417866326346190.387intergenic_variantHLA-DQA13e-92Tier 4: intronic/intergenic
rs19907602162267541C>T0.373missense_variantIFIH14e-15Tier 1: coding
rs112996008128192327TA>T0.253intergenic_variantPVT1 - RN7SKP2264e-11Tier 4: intronic/intergenic
rs45658701146328319T>C0.236intergenic_variantCREB3L1 - DGKZ7e-10Tier 4: intronic/intergenic
rs77739876135386348C>A,T0.487intron_variantAHI18e-10Tier 4: intronic/intergenic
rs340693911611067358GT>G0.196intron_variantCLEC16A1e-09Tier 4: intronic/intergenic
rs1244181108049414A>C,G,T0.05intron_variantGATA3-AS1, GATA35e-08Tier 4: intronic/intergenic
rs122570921089023070A>T0.05intergenic_variantFAS7e-08Tier 4: intronic/intergenic
rs672579591917047335T>A,C0.05intergenic_variantCPAMD8 - HAUS82e-07Tier 4: intronic/intergenic
rs98318943122081640A>C0.05intron_variantCD862e-07Tier 4: intronic/intergenic
rs168627803187970052G>A,T0.05intron_variantLINC019913e-07Tier 4: intronic/intergenic
rs801685062213196729A>G0.05intron_variantLINC01953 - SPAG16-DT3e-07Tier 4: intronic/intergenic
rs10071761540415509T>A,C,G0.05intron_variantRNU1-150P - TTC335e-07Tier 4: intronic/intergenic
rs80717891739850080C>T0.05intron_variantIKZF37e-07Tier 4: intronic/intergenic
rs21366131062834404C>G,T0.05intron_variantEGR2 - RNU6-543P7e-07Tier 4: intronic/intergenic
rs22109131157699203C>T0.05intron_variantFCRL39e-07Tier 4: intronic/intergenic
rs10905875106131814G>A,C0.05intron_variantRBM17 - PFKFB31e-06Tier 4: intronic/intergenic
rs129676781812805389G>A0.05intron_variantPTPN21e-06Tier 4: intronic/intergenic
rs1465837074122571262T>A0.05intergenic_variantIL2 - IL211e-06Tier 4: intronic/intergenic
rs47460911071647780A>C,T0.05intron_variantCDH232e-06Tier 4: intronic/intergenic
rs16895768566874704T>A,C0.05intron_variantMAST42e-06Tier 4: intronic/intergenic
rs56146007371459932T>C,G0.05intron_variantFOXP13e-06Tier 4: intronic/intergenic
rs122494671051320749G>A0.05intron_variantPRKG13e-06Tier 4: intronic/intergenic
rs76662864178365567G>A0.05intergenic_variantRNU1-45P - RNA5SP1733e-06Tier 4: intronic/intergenic
rs107335479880777T>A,C,G0.05intron_variantDMRT13e-06Tier 4: intronic/intergenic
rs39193628304365C>A,G,T0.05intergenic_variantLINC002994e-06Tier 4: intronic/intergenic
rs96094522232147927A>T0.05intergenic_variantAP1B1P1 - C22orf424e-06Tier 4: intronic/intergenic
rs122579611015275638G>A0.05intron_variantFAM171A15e-06Tier 4: intronic/intergenic
rs22513812129158371T>G0.05intron_variantMAP3K7CL5e-06Tier 4: intronic/intergenic
rs1126121161079379069G>A0.05intergenic_variantPPIF - ZCCHC247e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 40 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BCL6Orphanet:480541High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL6Orphanet:545Follicular lymphoma
BCL6Orphanet:98838Primary mediastinal large B-cell lymphoma
BCL6Orphanet:98839Intravascular large B-cell lymphoma
ACTA2Orphanet:2573Moyamoya disease
ACTA2Orphanet:404463Multisystemic smooth muscle dysfunction syndrome
ACTA2Orphanet:91387Familial thoracic aortic aneurysm and aortic dissection
IKZF2Orphanet:697389Combined immunodeficiency due to HELIOS deficiency
IKZF2Orphanet:699599ICHAD syndrome
IKZF3Orphanet:67038B-cell chronic lymphocytic leukemia
IKZF3Orphanet:699590Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3Orphanet:699593Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
CDH23Orphanet:231169Usher syndrome type 1
CDH23Orphanet:2965Prolactinoma
CDH23Orphanet:314777Familial isolated pituitary adenoma
CDH23Orphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CDH23Orphanet:91347TSH-secreting pituitary adenoma
CDH23Orphanet:96253Cushing disease
IFIH1Orphanet:51Aicardi-Goutières syndrome
IFIH1Orphanet:689231IFIH1-related hereditary spastic paraplegia
IFIH1Orphanet:85191Singleton-Merten dysplasia
AHI1Orphanet:220493Joubert syndrome with ocular defect
AHI1Orphanet:475Isolated Joubert syndrome
AHI1Orphanet:791Retinitis pigmentosa
EGR2Orphanet:101084Charcot-Marie-Tooth disease type 1D
EGR2Orphanet:64748Dejerine-Sottas syndrome
EGR2Orphanet:99951Charcot-Marie-Tooth disease type 4E
FOXP1Orphanet:391372FOXP1 Syndrome
FOXP1Orphanet:52417MALT lymphoma
FOXP1Orphanet:585877B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
GATA3Orphanet:2237Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3Orphanet:585936B-lymphoblastic leukemia/lymphoma with hyperdiploidy
HLA-DQA1Orphanet:391490Adult-onset myasthenia gravis
HLA-DQA1Orphanet:930Idiopathic achalasia
IL21Orphanet:477661IL21-related infantile inflammatory bowel disease
IL2RAOrphanet:169100Immunodeficiency due to CD25 deficiency
IL2RAOrphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
IL2RAOrphanet:85410Oligoarticular juvenile idiopathic arthritis
PTPN2Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN2Orphanet:85410Oligoarticular juvenile idiopathic arthritis

Cohort genes → proteins

38 cohort genes, 35 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only38

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BCL6HGNC:1001ENSG00000113916P41182B-cell lymphoma 6 proteingwas
ACTA2HGNC:130ENSG00000107796P62736Actin, aortic smooth musclegwas
IKZF2HGNC:13177ENSG00000030419Q9UKS7Zinc finger protein Heliosgwas
IKZF3HGNC:13178ENSG00000161405Q9UKT9Zinc finger protein Aiolosgwas
CDH23HGNC:13733ENSG00000107736Q9H251Cadherin-23gwas
ORMDL3HGNC:16038ENSG00000172057Q8N138ORM1-like protein 3gwas
CD86HGNC:1705ENSG00000114013P42081T-lymphocyte activation antigen CD86gwas
FCRL3HGNC:18506ENSG00000160856Q96P31Fc receptor-like protein 3gwas
IFIH1HGNC:18873ENSG00000115267Q9BYX4Interferon-induced helicase C domain-containing protein 1gwas
MAST4HGNC:19037ENSG00000069020O15021Microtubule-associated serine/threonine-protein kinase 4gwas
AHI1HGNC:21575ENSG00000135541Q8N157Jouberingwas
ADOHGNC:23506ENSG00000181915Q96SZ52-aminoethanethiol dioxygenasegwas
FAM171A1HGNC:23522ENSG00000148468Q5VUB5Protein FAM171A1gwas
AMBRA1HGNC:25990ENSG00000110497Q9C0C7Activating molecule in BECN1-regulated autophagy protein 1gwas
ZCCHC24HGNC:26911ENSG00000165424Q8N2G6Zinc finger CCHC domain-containing protein 24gwas
C22orf42HGNC:27160ENSG00000205856Q6IC83Uncharacterized protein C22orf42gwas
LINC01098HGNC:27731ENSG00000231171long intergenic non-protein coding RNA 1098gwas
LINC00299HGNC:27940ENSG00000236790Q6ZSB3Putative uncharacterized protein encoded by LINC00299gwas
CLEC16AHGNC:29013ENSG00000038532Q2KHT3Protein CLEC16Agwas
ATG13HGNC:29091ENSG00000175224O75143Autophagy-related protein 13gwas
NCKAP5HGNC:29847ENSG00000176771O14513Nck-associated protein 5gwas
HAUS8HGNC:30532ENSG00000131351Q9BT25HAUS augmin-like complex subunit 8gwas
TMEM72HGNC:31658ENSG00000187783A0PK05Transmembrane protein 72gwas
EGR2HGNC:3239ENSG00000122877P11161E3 SUMO-protein ligase EGR2gwas
MIR605HGNC:32861ENSG00000207813microRNA 605gwas
FASNHGNC:3594ENSG00000169710P49327Fatty acid synthasegwas
FOXP1HGNC:3823ENSG00000114861Q9H334Forkhead box protein P1gwas
GATA3HGNC:4172ENSG00000107485P23771Trans-acting T-cell-specific transcription factor GATA-3gwas
HLA-DQA1HGNC:4942ENSG00000196735P01909HLA class II histocompatibility antigen, DQ alpha 1 chaingwas
IL2HGNC:6001ENSG00000109471P60568Interleukin-2gwas
IL21HGNC:6005ENSG00000138684Q9HBE4Interleukin-21gwas
IL2RAHGNC:6008ENSG00000134460P01589Interleukin-2 receptor subunit alphagwas
MYO9BHGNC:7609ENSG00000099331Q13459Unconventional myosin-IXbgwas
PFKFB3HGNC:8874ENSG00000170525Q168756-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3gwas
BACH1HGNC:935ENSG00000156273O14867Transcription regulator protein BACH1gwas
PTGER4HGNC:9596ENSG00000171522P35408Prostaglandin E2 receptor EP4 subtypegwas
PTPN2HGNC:9650ENSG00000175354P17706Tyrosine-protein phosphatase non-receptor type 2gwas
PVT1HGNC:9709ENSG00000249859Pvt1 oncogenegwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BCL6B-cell lymphoma 6 proteinTranscriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.
ACTA2Actin, aortic smooth muscleActins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
IKZF2Zinc finger protein HeliosTranscription factor, which stabilizes the noninflammatory phenotype of regulatory T cells (Tregs).
IKZF3Zinc finger protein AiolosTranscription factor that plays an important role in the regulation of lymphocyte differentiation.
CDH23Cadherin-23Cadherins are calcium-dependent cell adhesion proteins.
ORMDL3ORM1-like protein 3Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels.
CD86T-lymphocyte activation antigen CD86Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
FCRL3Fc receptor-like protein 3Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation.
IFIH1Interferon-induced helicase C domain-containing protein 1Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and…
AHI1JouberinInvolved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.
ADO2-aminoethanethiol dioxygenasePlays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate.
FAM171A1Protein FAM171A1Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation.
AMBRA1Activating molecule in BECN1-regulated autophagy protein 1Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy.
CLEC16AProtein CLEC16ARegulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.
ATG13Autophagy-related protein 13Autophagy factor required for autophagosome formation and mitophagy.
HAUS8HAUS augmin-like complex subunit 8Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.
EGR2E3 SUMO-protein ligase EGR2Sequence-specific DNA-binding transcription factor.
FASNFatty acid synthaseFatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH.
FOXP1Forkhead box protein P1Transcriptional repressor.
GATA3Trans-acting T-cell-specific transcription factor GATA-3Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
HLA-DQA1HLA class II histocompatibility antigen, DQ alpha 1 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
IL2Interleukin-2Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance.
IL21Interleukin-21Cytokine with immunoregulatory activity.
IL2RAInterleukin-2 receptor subunit alphaReceptor for interleukin-2.
MYO9BUnconventional myosin-IXbMyosins are actin-based motor molecules with ATPase activity.
PFKFB36-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate.
BACH1Transcription regulator protein BACH1Transcriptional regulator that acts as a repressor or activator, depending on the context.
PTGER4Prostaglandin E2 receptor EP4 subtypeReceptor for prostaglandin E2 (PGE2).
PTPN2Tyrosine-protein phosphatase non-receptor type 2Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR.

Protein-family classification

Druggable: 10 · Difficult: 10 · Unknown: 18 · Druggable fraction: 0.26

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.

FamilyGenesFoldFDR
Complement17.0×0.421
Antibody/Immunoglobulin32.3×0.421
Transcription factor81.7×0.421
Phosphatase12.2×0.824
Enzyme (other)30.9×0.887
Scaffold/PPI20.9×0.887
Other/Unknown180.8×0.887
Kinase10.7×0.887
GPCR10.6×0.887

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BCL6Transcription factornoBTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
ACTA2Other/UnknownnoActin, Actin_CS, Actin/actin-like_CS
IKZF2Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
IKZF3Transcription factornoZnf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
CDH23Other/UnknownnoCadherin-like_dom, Cadherin-like_sf, Cadherin_CS
ORMDL3Other/UnknownnoORMDL
CD86Antibody/ImmunoglobulinyesIg_sub, Ig-like_dom, Ig_V-set
FCRL3Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
IFIH1Other/UnknownnoHelicase_C-like, Helicase/UvrB_N, DEATH-like_dom_sf
MAST4KinaseyesProt_kinase_dom, AGC-kinase_C, PDZ
AHI1Scaffold/PPInoSH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
ADOEnzyme (other)yes1.13.11.19RmlC_Cupin_sf, PCO/ADO, RmlC-like_jellyroll
FAM171A1Other/UnknownnoFAM171, FAM171_N, FAM171_C
AMBRA1Scaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
ZCCHC24Transcription factornoZnf_CCHC, Zn_knuckle_CX2CX3GHX4C, ZAR1/RTP1-5-like_Znf-3CxxC
C22orf42Other/UnknownnoDRICH1-like
LINC01098Other/Unknownno
LINC00299Other/Unknownno
CLEC16AOther/UnknownnoCLEC16A/TT9_N, CLEC16A/TT9, CLEC16A/TT9_C
ATG13Other/UnknownnoAtg13_N, HORMA_dom_sf, ATG13
NCKAP5Other/UnknownnoNckap5l, NCKAP5_C
HAUS8Other/Unknownno
TMEM72Other/UnknownnoTMEM72
EGR2Transcription factornoZnf_C2H2_type, EGR_N, Znf_C2H2_sf
MIR605Other/Unknownno
FASNEnzyme (other)yes2.3.1.39Thioesterase, Ac_transferase_dom_sf, Ppantetheine_attach_site
FOXP1Transcription factornoFork_head_dom, TF_fork_head_CS_2, FOXP-CC
GATA3Transcription factornoZnf_GATA, Znf_NHR/GATA, TF_GATA-2/3
HLA-DQA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
IL2Other/UnknownnoIL-2, 4_helix_cytokine-like_core, IL-2_CS
IL21Other/UnknownnoIL-15/IL-21_fam, 4_helix_cytokine-like_core
IL2RAComplementyesSushi_SCR_CCP_dom, IL-2_rcpt_alpha, Sushi/SCR/CCP_sf
MYO9BOther/UnknownnoIQ_motif_EF-hand-BS, RA_dom, RhoGAP_dom
PFKFB3Enzyme (other)yes2.7.1.105PG/BPGM_mutase_AS, 6Pfruct_kin, His_Pase_superF_clade-1
BACH1Transcription factorno3.6.4.12BTB/POZ_dom, bZIP_Maf, bZIP
PTGER4GPCRyesGPCR_Rhodpsn, Prostglndn_DP_rcpt, Prost_EP4_rcpt
PTPN2Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
PVT1Other/Unknownno

Expression context

Cohort genes with no expression data: 0.

35 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)38
unknown0

Top tissues across cohort

TissueCohort genes
granulocyte8
male germ line stem cell (sensu Vertebrata) in testis5
monocyte4
palpebral conjunctiva3
lymph node3
secondary oocyte3
primordial germ cell in gonad3
adrenal tissue3
left testis3
ventricular zone2
bone marrow cell2
mononuclear cell2
jejunal mucosa2
cervix squamous epithelium2
right hemisphere of cerebellum2
sperm2
inferior vagus X ganglion2
subthalamic nucleus2
right testis2
testis2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BCL6300ubiquitousmarkergastrocnemius, mucosa of stomach, blood
ACTA2289ubiquitousmarkercauda epididymis, blood vessel layer, saphenous vein
IKZF2232ubiquitousmarkerthymus, palpebral conjunctiva, amniotic fluid
IKZF3155broadmarkergranulocyte, lymph node, epithelium of nasopharynx
CDH23161broadmarkerventricular zone, left ovary, right ovary
ORMDL3256ubiquitousmarkerright lobe of liver, bone marrow cell, granulocyte
CD86218broadmarkermonocyte, mononuclear cell, leukocyte
FCRL3167tissue_specificmarkerileal mucosa, granulocyte, lymph node
IFIH1276ubiquitousmarkerpalpebral conjunctiva, parotid gland, jejunal mucosa
MAST4294ubiquitousmarkercervix squamous epithelium, cartilage tissue, squamous epithelium
AHI1276ubiquitousmarkerpituitary gland, calcaneal tendon, right hemisphere of cerebellum
ADO291ubiquitousyessperm, male germ cell, secondary oocyte
FAM171A1282ubiquitousmarkerinferior vagus X ganglion, middle temporal gyrus, subthalamic nucleus
AMBRA1279ubiquitousmarkeroocyte, secondary oocyte, cervix squamous epithelium
ZCCHC24283ubiquitousmarkerinferior vagus X ganglion, middle frontal gyrus, subthalamic nucleus
C22orf42100tissue_specificmarkersperm, islet of Langerhans, male germ line stem cell (sensu Vertebrata) in testis
LINC0109886markermale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, cortical plate
LINC00299157broadmarkergranulocyte, bone marrow cell, adrenal tissue
CLEC16A225ubiquitousmarkerleft testis, right testis, testis
ATG13286ubiquitousmarkerleft testis, right testis, testis
NCKAP5132broadmarkercorpus callosum, cerebellar vermis, ventricular zone
HAUS8167ubiquitousmarkerprimordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, granulocyte
TMEM72108tissue_specificmarkerrenal medulla, adult mammalian kidney, nasal cavity epithelium
EGR2143ubiquitousmarkergall bladder, tibial nerve, granulocyte
MIR60555yesstomach, kidney, adrenal tissue
FASN273ubiquitousmarkerright hemisphere of cerebellum, endometrium epithelium, skin of abdomen
FOXP1256ubiquitousmarkerpancreatic ductal cell, oviduct epithelium, cardia of stomach
GATA3220broadmarkerupper leg skin, skin of hip, endometrium epithelium
HLA-DQA1244broadmarkergall bladder, rectum, monocyte
IL292yesprimordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 17.

Hub genes (top 10 by interactor count)

SymbolInteractor count
FASN6,551
GATA35,990
AMBRA14,380
BCL63,984
IFIH13,706
CD863,672
IKZF33,285
EGR23,269
FOXP12,939
MYO9B2,911

Intra-cohort edges

ABSources
ADOEGR2string_interaction
AHI1HAUS8biogrid_interaction
AMBRA1ATG13string_interaction
BCL6FOXP1string_interaction
BCL6IL21string_interaction
C22orf42NCKAP5string_interaction
C22orf42TMEM72string_interaction
CLEC16AIFIH1string_interaction
CLEC16APTPN2string_interaction
FOXP1GATA3string_interaction
GATA3IKZF2string_interaction
IFIH1PTPN2string_interaction
IKZF2IKZF3biogrid_interaction
IKZF2IL2RAstring_interaction
IKZF3ORMDL3string_interaction
IL2IL2RAintact
IL2RAPTPN2string_interaction

Structural data

PDB: 24 · AlphaFold-only: 11 · No structure: 3

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
BCL6P41182246
IL2P6056837
FASNP4932734
HLA-DQA1P0190928
PFKFB3Q1687526
ATG13O7514315
PTPN2P1770614
ORMDL3Q8N13813
BACH1O1486712
IL2RAP0158910
PTGER4P3540810
IFIH1Q9BYX49
ADOQ96SZ59
IKZF2Q9UKS77
CD86P420817
CDH23Q9H2516
GATA3P237713
IL21Q9HBE43
AMBRA1Q9C0C72
MYO9BQ134592
MAST4O150211
AHI1Q8N1571
HAUS8Q9BT251
FOXP1Q9H3341

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
ACTA2P6273695.43
FCRL3Q96P3177.46
CLEC16AQ2KHT372.17
ZCCHC24Q8N2G669.49
TMEM72A0PK0557.48
FAM171A1Q5VUB557.15
C22orf42Q6IC8352.61
EGR2P1116149.02
IKZF3Q9UKT948.06
NCKAP5O1451343.93
LINC00299Q6ZSB333.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 144. Enrichment computed across 38 evidence-associated genes (26 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 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)287.8×0.023IL2, IL2RA
Interleukin-2 signaling273.2×0.023IL2, IL2RA
Interleukin receptor SHC signaling231.4×0.087IL2, IL2RA
SLIT2:ROBO1 increases RHOA activity1109.8×0.176MYO9B
Regulation of HMOX1 expression and activity187.8×0.176BACH1
ChREBP activates metabolic gene expression148.8×0.176FASN
Prostanoid ligand receptors148.8×0.176PTGER4
Interleukin-21 signaling143.9×0.176IL21
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis143.9×0.176FASN
Regulation of BACH1 activity139.9×0.176BACH1
Degradation of cysteine and homocysteine136.6×0.176ADO
Regulation of glycolysis by fructose 2,6-bisphosphate metabolism136.6×0.176PFKFB3
Regulation of CDH1 Function136.6×0.176ACTA2
CD28 dependent Vav1 pathway133.8×0.176CD86
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10133.8×0.176IFIH1
Regulation of IFNG signaling131.4×0.176PTPN2
Vitamin B5 (pantothenate) metabolism129.3×0.176FASN
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain129.3×0.176BCL6
TRAF3-dependent IRF activation pathway129.3×0.176IFIH1
Developmental Lineage of Mammary Stem Cells129.3×0.176GATA3
FOXO-mediated transcription of cell death genes127.4×0.176BCL6
Translocation of ZAP-70 to Immunological synapse124.4×0.176HLA-DQA1
Formation of the nephric duct124.4×0.176GATA3
Modulation of host responses by IFN-stimulated genes123.1×0.176IFIH1
Sulfur amino acid metabolism122.0×0.176ADO
NOTCH4 Intracellular Domain Regulates Transcription122.0×0.176ACTA2
Phosphorylation of CD3 and TCR zeta chains120.9×0.176HLA-DQA1
Transcriptional regulation of pluripotent stem cells120.9×0.176FOXP1
TP53 Regulates Transcription of Cell Death Genes120.9×0.176BCL6
NFE2L2 regulating anti-oxidant/detoxification enzymes120.9×0.176BACH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of B cell apoptotic process4197.7×1e-06BCL6, ORMDL3, FOXP1, IL2
T cell differentiation449.4×3e-04IKZF3, GATA3, IL2, PTPN2
positive regulation of B cell proliferation444.4×3e-04BCL6, FCRL3, IL2, IL21
regulation of CD4-positive, alpha-beta T cell proliferation2543.6×3e-04IL2, IL2RA
negative regulation of inflammatory response522.1×3e-04GATA3, IL2, IL2RA, PTGER4, PTPN2
positive regulation of regulatory T cell differentiation390.6×3e-04BCL6, AMBRA1, IL2
regulation of T cell homeostatic proliferation2362.4×6e-04IL2, IL2RA
positive regulation of immunoglobulin production346.6×0.002CD86, IL2, IL21
positive regulation of tissue remodeling2181.2×0.002IL2, IL21
response to mitochondrial depolarisation2181.2×0.002AMBRA1, ATG13
immune response69.1×0.002CD86, FCRL3, HLA-DQA1, IL2, IL2RA, PTGER4
interleukin-2-mediated signaling pathway2135.9×0.003IL2, IL2RA
T-helper 2 cell differentiation2120.8×0.004BCL6, GATA3
activated T cell proliferation2120.8×0.004IL2, IL2RA
mitophagy330.8×0.004AMBRA1, CLEC16A, ATG13
T follicular helper cell differentiation290.6×0.006FOXP1, IL21
regulation of B cell differentiation283.6×0.006IKZF3, FCRL3
positive regulation of autophagy320.1×0.010ORMDL3, AMBRA1, ATG13
type IV hypersensitivity1543.6×0.018GATA3
regulation of T cell tolerance induction1543.6×0.018IL2RA
rhombomere 3 structural organization1543.6×0.018EGR2
rhombomere 3 formation1543.6×0.018EGR2
rhombomere 5 structural organization1543.6×0.018EGR2
rhombomere 5 formation1543.6×0.018EGR2
regulation of toll-like receptor 9 signaling pathway1543.6×0.018FCRL3
regulation of memory T cell differentiation1543.6×0.018BCL6
positive regulation of hepatic stellate cell contraction1543.6×0.018ACTA2
regulation of macrophage colony-stimulating factor production1543.6×0.018FOXP1
negative regulation of interleukin-2-mediated signaling pathway1543.6×0.018PTPN2
negative regulation of positive thymic T cell selection1543.6×0.018PTPN2

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 4 · Phased (≥1): 8 · Undrugged: 30

Druggability breadth: 17 of 38 evidence-associated genes (45%) 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.

SymbolExample approved molecule
IKZF3POMALIDOMIDE
FASNRABEPRAZOLE
PTGER4DINOPROSTONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
PTGER494
FASN84
IKZF354
PTPN242
BCL622
IL222
PFKFB311
BACH113
ACTA200
IKZF200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
POMALIDOMIDE4IKZF3
LENALIDOMIDE4IKZF3
THALIDOMIDE4IKZF3
RABEPRAZOLE4FASN
PANTOPRAZOLE4FASN
OMEPRAZOLE4FASN
ORLISTAT4FASN
LANSOPRAZOLE4FASN
DINOPROSTONE4PTGER4
DINOPROST4PTGER4
IBERDOMIDE3IKZF3
EPIGALOCATECHIN GALLATE3FASN
SULFORAPHANE3BACH1
RALINEPAG3PTGER4
AMANOZINE2BCL6
AVADOMIDE2IKZF3
LUTEOLIN2FASN
DENIFANSTAT2FASN
FORMONONETIN2IL2
DISOGLUSIDE2IL2
BGC-20-1531 FREE BASE2PTGER4
GRAPIPRANT2PTGER4
BGC-20-15312PTGER4
PALUPIPRANT2PTGER4
OMIDENEPAG2PTGER4
BMS-9863102PTGER4
URSOLIC ACID2PTPN2
CHLOROGENIC ACID2PTPN2
OSUNPROTAFIB2PTPN2
TEGEPROTAFIB2PTPN2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

SymbolAssaysType breakdown
PTGER4288Binding:207, Functional:80, ADMET:1
PTPN2250Binding:246, ADMET:4
BCL6209Binding:202, Functional:7
FASN142Binding:136, Functional:6
BACH1139Binding:139
IKZF3101Binding:100, Functional:1
PFKFB352Binding:52
IL235Binding:34, ADMET:1
IKZF226Binding:26
MAST413Binding:13
HLA-DQA12Binding:2
IL2RA2Binding:2
ORMDL31Binding:1
IFIH11Binding:1
ATG131Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ADO1.13.11.19cysteamine dioxygenase
FASN2.3.1.39, 2.3.1.85[acyl-carrier-protein] S-malonyltransferase, fatty-acid synthase system
PFKFB32.7.1.105, 3.1.3.466-phosphofructo-2-kinase, fructose-2,6-bisphosphate 2-phosphatase
BACH13.6.4.12DNA helicase
PTPN23.1.3.48protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BCL6209
IKZF3101
FASN142
BACH1139
PTGER4288
PTPN2250

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; 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.

CompoundMax phaseCohort target (bioactivity)
POMALIDOMIDE4IKZF3
LENALIDOMIDE4IKZF3
THALIDOMIDE4IKZF3
RABEPRAZOLE4FASN
PANTOPRAZOLE4FASN
OMEPRAZOLE4FASN
ORLISTAT4FASN
LANSOPRAZOLE4FASN
DINOPROSTONE4PTGER4
DINOPROST4PTGER4
IBERDOMIDE3IKZF3
EPIGALOCATECHIN GALLATE3FASN
SULFORAPHANE3BACH1
RALINEPAG3PTGER4
AMANOZINE2BCL6
AVADOMIDE2IKZF3
LUTEOLIN2FASN
DENIFANSTAT2FASN
FORMONONETIN2IL2
DISOGLUSIDE2IL2
BGC-20-1531 FREE BASE2PTGER4
GRAPIPRANT2PTGER4
BGC-20-15312PTGER4
PALUPIPRANT2PTGER4
OMIDENEPAG2PTGER4
BMS-9863102PTGER4
URSOLIC ACID2PTPN2
CHLOROGENIC ACID2PTPN2
OSUNPROTAFIB2PTPN2
TEGEPROTAFIB2PTPN2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3IKZF3, FASN, PTGER4
BPhased (≥1) drug, not yet approved5BCL6, IL2, PFKFB3, BACH1, PTPN2
CDruggable family + PDB, no drug5CD86, MAST4, ADO, HLA-DQA1, IL2RA
DDruggable family + AlphaFold only, no drug1FCRL3
EDifficult family or no structure, no drug24ACTA2, IKZF2, CDH23, ORMDL3, IFIH1, AHI1, FAM171A1, AMBRA1, ZCCHC24, C22orf42 (+14 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
CLEC16A0PTPN2
IL210BCL6
ACTA20—
IKZF226—
CDH230—
ORMDL31—
CD860—
FCRL30—
IFIH11—
MAST413—
AHI10—
ADO0—
FAM171A10—
AMBRA10—
ZCCHC240—
C22orf420—
LINC010980—
LINC002990—
ATG131—
NCKAP50—
HAUS80—
TMEM720—
EGR20—
MIR6050—
FOXP10—
GATA30—
HLA-DQA12—
IL2RA2—
MYO9B0—
PVT10—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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Sources 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot