Chylomicron retention disease

Summary

Chylomicron retention disease (MONDO:0009528) is a disease caused by SAR1B (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SAR1B (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 17
• Phenotypes (HPO): 20
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		55	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0002014	Diarrhea	Obligate (100%)
HP:0003146	Hypocholesterolemia	Obligate (100%)
HP:0000488	Retinopathy	Very frequent (80-99%)
HP:0002570	Steatorrhea	Very frequent (80-99%)
HP:0002630	Fat malabsorption	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0006565	Increased hepatocellular lipid droplets	Frequent (30-79%)
HP:0100508	Abnormality of vitamin metabolism	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0003458	EMG: myopathic abnormalities	Occasional (5-29%)
HP:0002155	Hypertriglyceridemia	Excluded (0%)
HP:0001284	Areflexia	Very rare (<1-4%)
HP:0001927	Acanthocytosis	Very rare (<1-4%)
HP:0003198	Myopathy	Very rare (<1-4%)
HP:0010831	Impaired proprioception	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chylomicron retention disease
Mondo ID	MONDO:0009528
MeSH	C535460
OMIM	246700
Orphanet	71
DOID	DOID:0060357
ICD-11	1447416932
SNOMED CT	702364003
UMLS	C0795956
MedGen	208651
GARD	0009683
Is cancer (heuristic)	no

Also known as: Anderson disease · chylomicron retention disease · CMRD · CRD · hypobetalipoproteinemia with accumulation of apolipoprotein B-like protein in intestinal cells

Data availability: 17 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › hypolipoproteinemia › hypobetalipoproteinemia › chylomicron retention disease

Related subtypes (3): abetalipoproteinemia, familial hypobetalipoproteinemia 2, familial hypobetalipoproteinemia 1

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

17 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 pathogenic/likely pathogenic, 2 benign, 2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162261	NM_016356.5(DCDC2):c.346G>T (p.Glu116Ter)	DCDC2	Pathogenic	criteria provided, single submitter
1325033	NM_016103.4(SAR1B):c.247C>T (p.Arg83Ter)	SAR1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2922	NM_016103.4(SAR1B):c.109G>A (p.Gly37Arg)	SAR1B	Pathogenic	no assertion criteria provided
2923	NM_016103.4(SAR1B):c.409G>A (p.Asp137Asn)	SAR1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2924	NM_016103.4(SAR1B):c.75_76del (p.Thr25_Gly26insTer)	SAR1B	Pathogenic	no assertion criteria provided
2925	NM_016103.4(SAR1B):c.537T>A (p.Ser179Arg)	SAR1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2926	NM_016103.4(SAR1B):c.555_558dup (p.Gly187fs)	SAR1B	Pathogenic	no assertion criteria provided
2927	NM_016103.4(SAR1B):c.349-1G>C	SAR1B	Pathogenic	no assertion criteria provided
2928	NM_016103.4(SAR1B):c.364G>T (p.Glu122Ter)	SAR1B	Pathogenic	no assertion criteria provided
2929	NM_016103.4(SAR1B):c.554G>T (p.Gly185Val)	SAR1B	Pathogenic	criteria provided, single submitter
3608690	NM_016103.4(SAR1B):c.209dup (p.Phe71fs)	SAR1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
985564	NM_016103.4(SAR1B):c.336del (p.Glu113fs)	SAR1B	Pathogenic	criteria provided, multiple submitters, no conflicts
2506539	GRCh37/hg19 5q31.1(chr5:133956623-133959709)	SAR1B	Likely pathogenic	criteria provided, single submitter
3254897	NM_016103.4(SAR1B):c.244+1_244+2del	SAR1B	Likely pathogenic	criteria provided, single submitter
522346	NM_016103.4(SAR1B):c.280A>C (p.Asn94His)	SAR1B	Uncertain significance	criteria provided, single submitter
1170812	NM_016103.4(SAR1B):c.133C>T (p.Leu45=)	SAR1B	Benign	criteria provided, multiple submitters, no conflicts
1236079	NM_016103.4(SAR1B):c.480+18del	SAR1B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SAR1B	Strong	Autosomal recessive	chylomicron retention disease	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SAR1B	Orphanet:71	Chylomicron retention disease
DCDC2	Orphanet:480556	Isolated neonatal sclerosing cholangitis
DCDC2	Orphanet:84081	Senior-Boichis syndrome
DCDC2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SAR1B	HGNC:10535	ENSG00000152700	Q9Y6B6	Small COPII coat GTPase SAR1B	gencc,clinvar
DCDC2	HGNC:18141	ENSG00000146038	Q9UHG0	Doublecortin domain-containing protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SAR1B	Small COPII coat GTPase SAR1B	Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport.
DCDC2	Doublecortin domain-containing protein 2	Protein that plays a role in the inhibition of canonical Wnt signaling pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SAR1B	Other/Unknown	no		Small_GTP-bd, Small_GTPase_SAR1, Small_GTPase_ARF/SAR
DCDC2	Other/Unknown	no		Doublecortin_dom, DCDC2_DCX_dom2, Doublecortin_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
jejunal mucosa	1
skeletal muscle tissue of rectus abdominis	1
oocyte	1
oviduct epithelium	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SAR1B	287	ubiquitous	marker	jejunal mucosa, skeletal muscle tissue of rectus abdominis, biceps brachii
DCDC2	156	broad	marker	secondary oocyte, oocyte, oviduct epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SAR1B	2,241
DCDC2	1,025

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SAR1B	Q9Y6B6	4
DCDC2	Q9UHG0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 2 evidence-associated genes (1 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 1 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	1142.0×	0.018	SAR1B
Plasma lipoprotein assembly	1	713.8×	0.018	SAR1B
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	393.8×	0.018	SAR1B
Cargo concentration in the ER	1	335.9×	0.018	SAR1B
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.018	SAR1B
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.021	SAR1B
COPII-mediated vesicle transport	1	163.1×	0.024	SAR1B
Metabolism of steroids	1	137.6×	0.024	SAR1B
ER to Golgi Anterograde Transport	1	132.8×	0.024	SAR1B
SARS-CoV-2-host interactions	1	119.0×	0.024	SAR1B
Transport to the Golgi and subsequent modification	1	102.9×	0.025	SAR1B
MHC class II antigen presentation	1	89.2×	0.025	SAR1B
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.025	SAR1B
SARS-CoV-2 Infection	1	80.4×	0.026	SAR1B
Class I MHC mediated antigen processing & presentation	1	70.1×	0.028	SAR1B
Asparagine N-linked glycosylation	1	60.1×	0.030	SAR1B
SARS-CoV Infections	1	55.4×	0.031	SAR1B
Membrane Trafficking	1	37.1×	0.043	SAR1B
Vesicle-mediated transport	1	34.8×	0.044	SAR1B
Metabolism of lipids	1	31.6×	0.044	SAR1B
Viral Infection Pathways	1	30.8×	0.044	SAR1B
Adaptive Immune System	1	29.8×	0.044	SAR1B
Transport of small molecules	1	25.1×	0.049	SAR1B
Infectious disease	1	24.8×	0.049	SAR1B
Post-translational protein modification	1	19.2×	0.060	SAR1B
Disease	1	13.1×	0.083	SAR1B
Immune System	1	13.0×	0.083	SAR1B
Metabolism of proteins	1	12.4×	0.084	SAR1B
Metabolism	1	11.6×	0.086	SAR1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lipid export from cell	1	4213.0×	0.004	SAR1B
regulation of lipid transport	1	2106.5×	0.004	SAR1B
antigen processing and presentation of peptide antigen via MHC class I	1	1685.2×	0.004	SAR1B
obsolete regulation of COPII vesicle coating	1	1685.2×	0.004	SAR1B
regulation of TORC1 signaling	1	842.6×	0.005	SAR1B
cellular response to leucine starvation	1	702.2×	0.005	SAR1B
vesicle organization	1	561.7×	0.005	SAR1B
lipoprotein transport	1	495.6×	0.005	SAR1B
COPII-coated vesicle cargo loading	1	495.6×	0.005	SAR1B
regulation of Wnt signaling pathway	1	443.5×	0.005	DCDC2
COPII vesicle coat assembly	1	351.1×	0.006	SAR1B
regulation of cilium assembly	1	300.9×	0.007	DCDC2
membrane organization	1	255.3×	0.007	SAR1B
dendrite morphogenesis	1	216.1×	0.008	DCDC2
positive regulation of smoothened signaling pathway	1	210.7×	0.008	DCDC2
lipid homeostasis	1	168.5×	0.008	SAR1B
negative regulation of TORC1 signaling	1	162.0×	0.008	SAR1B
cellular defense response	1	159.0×	0.008	DCDC2
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.018	SAR1B
neuron migration	1	66.9×	0.018	DCDC2
sensory perception of sound	1	50.5×	0.023	DCDC2
cilium assembly	1	36.8×	0.029	DCDC2
intracellular protein transport	1	32.4×	0.032	SAR1B
intracellular signal transduction	1	19.1×	0.052	DCDC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SAR1B	0	0
DCDC2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SAR1B, DCDC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SAR1B	0	—
DCDC2	0	—

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
NCT05208879	Not specified	COMPLETED	CArotenoid in hypoChOlesterolemia