Inflammatory bowel disease 28
diseaseOn this page
Also known as IBD28IL10RA inflammatory bowel diseaseinflammatory bowel disease 28, autosomal recessiveinflammatory bowel disease 28, early onset, autosomal recessiveinflammatory bowel disease caused by mutation in IL10RAinflammatory bowel disease type 28inflammatory bowel disease, early-onset, autosomal recessive
Summary
Inflammatory bowel disease 28 (MONDO:0013153) is a disease caused by IL10RA (GenCC Strong), with 4 cohort genes.
At a glance
- Causal gene: IL10RA (GenCC Strong)
- Cohort genes: 4
- ClinVar variants: 450
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | inflammatory bowel disease 28 |
| Mondo ID | MONDO:0013153 |
| MeSH | C567728 |
| OMIM | 613148 |
| DOID | DOID:0110899 |
| NCIT | C164676 |
| UMLS | C2751053 |
| MedGen | 442630 |
| GARD | 0018343 |
| Is cancer (heuristic) | no |
Also known as: IBD28 · IL10RA inflammatory bowel disease · inflammatory bowel disease 28 · inflammatory bowel disease 28, autosomal recessive · inflammatory bowel disease 28, early onset, autosomal recessive · inflammatory bowel disease caused by mutation in IL10RA · inflammatory bowel disease type 28 · inflammatory bowel disease, early-onset, autosomal recessive
Data availability: 450 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › IL10-related early-onset inflammatory bowel disease › inflammatory bowel disease 28
Related subtypes (1): inflammatory bowel disease 25
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
450 retrieved; paginated sample, class counts are floors:
187 uncertain significance, 172 likely benign, 33 conflicting classifications of pathogenicity, 19 benign, 17 pathogenic, 14 benign/likely benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1074445 | NM_001558.4(IL10RA):c.756C>A (p.Tyr252Ter) | IL10RA | Pathogenic | criteria provided, single submitter |
| 1435397 | NM_001558.4(IL10RA):c.618dup (p.Pro207fs) | IL10RA | Pathogenic | criteria provided, single submitter |
| 1478637 | NM_001558.4(IL10RA):c.769C>T (p.Gln257Ter) | IL10RA | Pathogenic | criteria provided, single submitter |
| 14814 | NM_001558.4(IL10RA):c.421G>A (p.Gly141Arg) | IL10RA | Pathogenic | no assertion criteria provided |
| 14815 | NM_001558.4(IL10RA):c.251C>T (p.Thr84Ile) | IL10RA | Pathogenic | no assertion criteria provided |
| 1978943 | NM_001558.4(IL10RA):c.258_279dup (p.Asn94fs) | IL10RA | Pathogenic | criteria provided, single submitter |
| 2022922 | NM_001558.4(IL10RA):c.439_452del (p.Arg147fs) | IL10RA | Pathogenic | criteria provided, single submitter |
| 2137257 | NM_001558.4(IL10RA):c.470A>G (p.Tyr157Cys) | IL10RA | Pathogenic | criteria provided, single submitter |
| 2729159 | NM_001558.4(IL10RA):c.501T>G (p.Tyr167Ter) | IL10RA | Pathogenic | criteria provided, single submitter |
| 2751753 | NM_001558.4(IL10RA):c.349C>T (p.Arg117Cys) | IL10RA | Pathogenic | criteria provided, single submitter |
| 3341480 | NM_001558.4(IL10RA):c.493C>T (p.Arg165Ter) | IL10RA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3656591 | NM_001558.4(IL10RA):c.3G>A (p.Met1Ile) | IL10RA | Pathogenic | criteria provided, single submitter |
| 3721097 | NM_001558.4(IL10RA):c.99G>A (p.Trp33Ter) | IL10RA | Pathogenic | criteria provided, single submitter |
| 39430 | NM_001558.4(IL10RA):c.784C>T (p.Arg262Cys) | IL10RA | Pathogenic | criteria provided, single submitter |
| 39432 | NM_001558.4(IL10RA):c.301C>T (p.Arg101Trp) | IL10RA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 830051 | NM_001558.4(IL10RA):c.537G>A (p.Thr179=) | IL10RA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 830052 | NM_001558.4(IL10RA):c.634C>T (p.Arg212Ter) | IL10RA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 943905 | NM_001558.4(IL10RA):c.506T>C (p.Ile169Thr) | IL10RA | Pathogenic | criteria provided, single submitter |
| 1048075 | NM_001558.4(IL10RA):c.1_67+1del | LOC130006833 | Pathogenic | no assertion criteria provided |
| 831101 | NC_000011.9:g.(?117856768)(118972385_?)del | SLC37A4 | Pathogenic | criteria provided, single submitter |
| 1471309 | NM_001558.4(IL10RA):c.68-1G>A | IL10RA | Likely pathogenic | criteria provided, single submitter |
| 4846816 | NM_001558.4(IL10RA):c.127del (p.Leu43fs) | IL10RA | Likely pathogenic | criteria provided, single submitter |
| 4849293 | NM_001558.4(IL10RA):c.67+1G>A | IL10RA | Likely pathogenic | criteria provided, single submitter |
| 802794 | NM_001558.4(IL10RA):c.787C>T (p.Arg263Ter) | IL10RA | Likely pathogenic | criteria provided, single submitter |
| 1047917 | NC_000011.10:g.117986319_117986651del | LOC130006833 | Likely pathogenic | criteria provided, single submitter |
| 1024640 | NM_001558.4(IL10RA):c.1400C>T (p.Ser467Leu) | IL10RA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1126309 | NM_001558.4(IL10RA):c.301C>A (p.Arg101=) | IL10RA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1717803 | NM_001558.4(IL10RA):c.742G>A (p.Gly248Arg) | IL10RA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1906330 | NM_001558.4(IL10RA):c.1064T>A (p.Val355Glu) | IL10RA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1936545 | NM_001558.4(IL10RA):c.1594A>G (p.Ser532Gly) | IL10RA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| IL10RA | Strong | Autosomal recessive | inflammatory bowel disease 28 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| IL10RA | Orphanet:238569 | Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome |
| SLC37A4 | Orphanet:79259 | Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib |
| APOC3 | Orphanet:181428 | Familial Hyperalphalipoproteinemia |
| ARCN1 | Orphanet:659702 | Intrauterine growth retardation-micrognathia-short stature-facial dysmorphism-rhizomelic shortening syndrome |
Cohort genes → proteins
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| IL10RA | HGNC:5964 | ENSG00000110324 | Q13651 | Interleukin-10 receptor subunit alpha | gencc,clinvar |
| SLC37A4 | HGNC:4061 | ENSG00000137700 | O43826 | Glucose-6-phosphate exchanger SLC37A4 | clinvar |
| APOC3 | HGNC:610 | ENSG00000110245 | P02656 | Apolipoprotein C-III | clinvar |
| ARCN1 | HGNC:649 | ENSG00000095139 | P48444 | Coatomer subunit delta | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| IL10RA | Interleukin-10 receptor subunit alpha | Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. |
| SLC37A4 | Glucose-6-phosphate exchanger SLC37A4 | Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum. |
| APOC3 | Apolipoprotein C-III | Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. |
| ARCN1 | Coatomer subunit delta | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to t… |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5
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.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Transporter | 1 | 19.4× | 0.151 |
| Antibody/Immunoglobulin | 1 | 7.3× | 0.195 |
| Other/Unknown | 2 | 0.9× | 0.769 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| IL10RA | Antibody/Immunoglobulin | yes | FN3_dom, Ig-like_fold, FN3_sf | |
| SLC37A4 | Transporter | yes | Sugar_P_transporter, MFS, MFS_dom | |
| APOC3 | Other/Unknown | no | Apo-CIII, Apo_CIII_sf | |
| ARCN1 | Other/Unknown | no | Longin-like_dom_sf, AP_mu_sigma_su, Coatomer_dsu |
Expression context
Cohort genes with no expression data: 0.
4 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| liver | 2 |
| right lobe of liver | 2 |
| granulocyte | 1 |
| leukocyte | 1 |
| mononuclear cell | 1 |
| duodenum | 1 |
| jejunal mucosa | 1 |
| body of pancreas | 1 |
| islet of Langerhans | 1 |
| stromal cell of endometrium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| IL10RA | 234 | broad | marker | granulocyte, leukocyte, mononuclear cell |
| SLC37A4 | 134 | ubiquitous | marker | right lobe of liver, liver, duodenum |
| APOC3 | 156 | tissue_specific | marker | jejunal mucosa, right lobe of liver, liver |
| ARCN1 | 299 | ubiquitous | marker | stromal cell of endometrium, islet of Langerhans, body of pancreas |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ARCN1 | 3,064 |
| IL10RA | 2,462 |
| APOC3 | 1,895 |
| SLC37A4 | 1,242 |
Structural data
PDB: 3 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SLC37A4 | O43826 | 25 |
| IL10RA | Q13651 | 7 |
| APOC3 | P02656 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ARCN1 | P48444 | 84.25 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Chylomicron assembly | 1 | 380.7× | 0.015 | APOC3 |
| Chylomicron remodeling | 1 | 380.7× | 0.015 | APOC3 |
| HDL remodeling | 1 | 380.7× | 0.015 | APOC3 |
| Plasma lipoprotein assembly | 1 | 237.9× | 0.018 | APOC3 |
| Plasma lipoprotein remodeling | 1 | 158.6× | 0.020 | APOC3 |
| Metabolism of fat-soluble vitamins | 1 | 126.9× | 0.020 | APOC3 |
| Nuclear events stimulated by ALK signaling in cancer | 1 | 108.8× | 0.020 | IL10RA |
| Visual phototransduction | 1 | 86.5× | 0.020 | APOC3 |
| Retinoid metabolism and transport | 1 | 82.8× | 0.020 | APOC3 |
| Interleukin-10 signaling | 1 | 77.7× | 0.020 | IL10RA |
| Plasma lipoprotein assembly, remodeling, and clearance | 1 | 76.1× | 0.020 | APOC3 |
| Metabolism of vitamins and cofactors | 1 | 38.8× | 0.033 | APOC3 |
| COPI-dependent Golgi-to-ER retrograde traffic | 1 | 37.0× | 0.033 | ARCN1 |
| COPI-mediated anterograde transport | 1 | 36.6× | 0.033 | ARCN1 |
| Sensory Perception | 1 | 31.7× | 0.035 | APOC3 |
| Transport of small molecules | 1 | 8.4× | 0.122 | APOC3 |
| Metabolism | 1 | 3.9× | 0.237 | APOC3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| negative regulation of high-density lipoprotein particle clearance | 1 | 4213.0× | 0.007 | APOC3 |
| cerebellar Purkinje cell layer maturation | 1 | 2106.5× | 0.007 | ARCN1 |
| negative regulation of cholesterol import | 1 | 1404.3× | 0.007 | APOC3 |
| negative regulation of very-low-density lipoprotein particle clearance | 1 | 1053.2× | 0.007 | APOC3 |
| negative regulation of lipid metabolic process | 1 | 842.6× | 0.007 | APOC3 |
| negative regulation of triglyceride catabolic process | 1 | 702.2× | 0.007 | APOC3 |
| negative regulation of very-low-density lipoprotein particle remodeling | 1 | 702.2× | 0.007 | APOC3 |
| glucose-6-phosphate transport | 1 | 702.2× | 0.007 | SLC37A4 |
| chylomicron remnant clearance | 1 | 702.2× | 0.007 | APOC3 |
| Golgi localization | 1 | 526.6× | 0.007 | ARCN1 |
| negative regulation of receptor-mediated endocytosis | 1 | 468.1× | 0.007 | APOC3 |
| intestinal epithelial structure maintenance | 1 | 468.1× | 0.007 | IL10RA |
| ubiquitin-dependent endocytosis | 1 | 468.1× | 0.007 | IL10RA |
| negative regulation of low-density lipoprotein particle clearance | 1 | 383.0× | 0.008 | APOC3 |
| regulation of Cdc42 protein signal transduction | 1 | 351.1× | 0.008 | APOC3 |
| interleukin-10-mediated signaling pathway | 1 | 351.1× | 0.008 | IL10RA |
| very-low-density lipoprotein particle assembly | 1 | 300.9× | 0.008 | APOC3 |
| phosphate ion transmembrane transport | 1 | 300.9× | 0.008 | SLC37A4 |
| phospholipid efflux | 1 | 280.9× | 0.008 | APOC3 |
| lipoprotein metabolic process | 1 | 234.1× | 0.009 | APOC3 |
| reverse cholesterol transport | 1 | 234.1× | 0.009 | APOC3 |
| negative regulation of fatty acid biosynthetic process | 1 | 221.7× | 0.009 | APOC3 |
| negative regulation of lipid catabolic process | 1 | 210.7× | 0.009 | APOC3 |
| triglyceride catabolic process | 1 | 200.6× | 0.009 | APOC3 |
| high-density lipoprotein particle remodeling | 1 | 200.6× | 0.009 | APOC3 |
| pigmentation | 1 | 175.5× | 0.010 | ARCN1 |
| regulation of synapse organization | 1 | 162.0× | 0.010 | IL10RA |
| cholesterol efflux | 1 | 131.7× | 0.012 | APOC3 |
| triglyceride homeostasis | 1 | 120.4× | 0.013 | APOC3 |
| triglyceride metabolic process | 1 | 110.9× | 0.013 | APOC3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4
Druggability breadth: 3 of 4 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| IL10RA | 0 | 0 |
| SLC37A4 | 0 | 0 |
| APOC3 | 0 | 0 |
| ARCN1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SLC37A4 | 5 | Binding:5 |
| APOC3 | 1 | Binding:1 |
| ARCN1 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 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.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | IL10RA, SLC37A4 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | APOC3, ARCN1 |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| IL10RA | 0 | — |
| SLC37A4 | 5 | — |
| APOC3 | 1 | — |
| ARCN1 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.