Refractory celiac disease

Summary

Refractory celiac disease (MONDO:0018353) is a disease with 2 GWAS associations across 1 studies and 1 clinical trial. A subtype of intestinal disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• GWAS associations: 2
• Phenotypes (HPO): 28
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0011473	Villous atrophy	Obligate (100%)
HP:0030057	Autoimmune antibody positivity	Very frequent (80-99%)
HP:0002853	Increased proportion of HLA DR+ T cells	Very frequent (80-99%)
HP:0002028	Chronic diarrhea	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002024	Malabsorption	Frequent (30-79%)
HP:0001935	Microcytic anemia	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0011123	Inflammatory abnormality of the skin	Frequent (30-79%)
HP:0003075	Hypoproteinemia	Frequent (30-79%)
HP:0001891	Iron deficiency anemia	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0004395	Malnutrition	Frequent (30-79%)
HP:0033143	Jejunitis	Frequent (30-79%)
HP:0003073	Hypoalbuminemia	Frequent (30-79%)
HP:0000939	Osteoporosis	Occasional (5-29%)
HP:0000707	Abnormality of the nervous system	Occasional (5-29%)
HP:0002901	Hypocalcemia	Occasional (5-29%)
HP:0002917	Hypomagnesemia	Occasional (5-29%)
HP:0002148	Hypophosphatemia	Occasional (5-29%)
HP:0010639	Elevated alkaline phosphatase of bone origin	Occasional (5-29%)
HP:0012052	Low serum calcitriol	Occasional (5-29%)
HP:0025409	Abnormal spleen physiology	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0002243	Protein-losing enteropathy	Occasional (5-29%)
HP:0001897	Normocytic anemia	Very rare (<1-4%)
HP:0001972	Macrocytic anemia	Very rare (<1-4%)
HP:0002665	Lymphoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	refractory celiac disease
Mondo ID	MONDO:0018353
EFO	EFO:0009266
Orphanet	398063
UMLS	C4749333
MedGen	1670595
GARD	0021640
NORD	1653
Is cancer (heuristic)	no

Also known as: intractable celiac sprue · intractable coeliac sprue · refractory CD · refractory sprue · type I refractory sprue · type II refractory sprue

Data availability: 2 GWAS associations (1 study).

Disease family

This is a subtype of intestinal disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › refractory celiac disease

Related subtypes (57): intestinal atresia, steatorrhea, angiodysplasia of intestine, endometriosis of intestine, hypertrophic pyloric stenosis, mucocele of appendix, gastroenteritis, diverticulitis, intestinal obstruction, postgastrectomy syndrome, chronic intestinal vascular insufficiency, bowel dysfunction, irritable bowel syndrome, Whipple disease, inflammatory bowel disease, intestinal polyp, necrotizing enterocolitis, intestinal perforation, neurogenic bowel, pneumatosis cystoides intestinalis, volvulus of midgut, abetalipoproteinemia, aplasia cutis congenita-intestinal lymphangiectasia syndrome, trichohepatoenteric syndrome, protein-losing enteropathy, chronic diarrhea with villous atrophy, Satoyoshi syndrome, glucose-galactose malabsorption, congenital diarrhea 7 with exudative enteropathy, chronic atrial and intestinal dysrhythmia, congenital enterocyte heparan sulfate deficiency, short bowel syndrome, intractable diarrhea-choanal atresia-eye anomalies syndrome, solitary rectal ulcer syndrome, NK-cell enteropathy, chronic intestinal failure, intestinal lymphangiectasia, eosinophilic gastrointestinal disease, cryptogenic multifocal ulcerous stenosing enteritis, chronic enteropathy associated with SLCO2A1 gene, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, malakoplakia, malabsorption syndrome, ischemic bowel disorder, intestinal neoplasm, intestinal motility disease, 4-hydroxyphenylacetic aciduria, parasitic intestinal disorder, Aeromonas hydrophila intestinal disease, large intestine disorder, small intestine disorder, primary desmosis coli, isolated mesenteric vein thrombosis, collagenous sprue, visceral leiomyopathy, African degenerative, intestinal dysmotility syndrome, intestinal fistula

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2041570	2e-08	ADCYAP1R1 - NEUROD6	A	2.36
HLA-DQ2	5e-08		?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005928	Hrdlickova B	2018	38	0	A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2041570	7	31159653	G>A	0.41	intron_variant	ADCYAP1R1 - NEUROD6	2e-08	Tier 4: intronic/intergenic
HLA-DQ2							5e-08	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

No druggable-target or therapeutic data for this disease’s cohort.

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07556328	Not specified	RECRUITING	Histomolecular Profiling in Small-Bowel Diseases