Abetalipoproteinemia

Summary

Abetalipoproteinemia (MONDO:0008692) is a disease caused by MTTP (GenCC Definitive), with 1 cohort gene and 3 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MTTP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 346
• Phenotypes (HPO): 63
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

63 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000707	Abnormality of the nervous system	Very frequent (80-99%)
HP:0001927	Acanthocytosis	Very frequent (80-99%)
HP:0002570	Steatorrhea	Very frequent (80-99%)
HP:0002630	Fat malabsorption	Very frequent (80-99%)
HP:0025201	Abnormal circulating apolipoprotein concentration	Very frequent (80-99%)
HP:0100513	Low levels of vitamin E	Very frequent (80-99%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000551	Color vision defect	Frequent (30-79%)
HP:0000662	Nyctalopia	Frequent (30-79%)
HP:0001284	Areflexia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001923	Reticulocytosis	Frequent (30-79%)
HP:0002028	Chronic diarrhea	Frequent (30-79%)
HP:0002904	Hyperbilirubinemia	Frequent (30-79%)
HP:0003073	Hypoalbuminemia	Frequent (30-79%)
HP:0003146	Hypocholesterolemia	Frequent (30-79%)
HP:0003233	Decreased HDL cholesterol concentration	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003563	Decreased LDL cholesterol concentration	Frequent (30-79%)
HP:0004905	Low levels of vitamin A	Frequent (30-79%)
HP:0007703	Abnormality of retinal pigmentation	Frequent (30-79%)
HP:0012153	Hypotriglyceridemia	Frequent (30-79%)
HP:0100512	Low levels of vitamin D	Frequent (30-79%)
HP:0000510	Rod-cone dystrophy	Occasional (5-29%)
HP:0000575	Scotoma	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001310	Dysmetria	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0001761	Pes cavus	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002066	Gait ataxia	Occasional (5-29%)
HP:0002136	Broad-based gait	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002403	Positive Romberg sign	Occasional (5-29%)
HP:0002493	Upper motor neuron dysfunction	Occasional (5-29%)
HP:0002495	Impaired vibratory sensation	Occasional (5-29%)
HP:0002751	Kyphoscoliosis	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0003198	Myopathy	Occasional (5-29%)
HP:0003376	Steppage gait	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0006858	Impaired distal proprioception	Occasional (5-29%)
HP:0007894	Hypopigmentation of the fundus	Occasional (5-29%)
HP:0008151	Prolonged prothrombin time	Occasional (5-29%)
HP:0009053	Distal lower limb muscle weakness	Occasional (5-29%)
HP:0010831	Impaired proprioception	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	abetalipoproteinemia
Mondo ID	MONDO:0008692
MeSH	D000012
OMIM	200100
Orphanet	14
DOID	DOID:1386
ICD-11	1117838449
NCIT	C84525
SNOMED CT	190787008
UMLS	C0000744
MedGen	1253
GARD	0000005
NORD	703
Is cancer (heuristic)	no

Also known as: abetalipoproteinemia · abetalipoproteinemia neuropathy · ABL · apolipoprotein B deficiency · Bassen Kornzweig syndrome · Bassen-Kornzweig disease · Betalipoprotein deficiency disease · congenital betalipoprotein deficiency syndrome · homozygous familial hypobetalipoproteinemia

Data availability: 346 ClinVar variants · 5 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › abetalipoproteinemia

Related subtypes (22): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, hereditary cryohydrocytosis with reduced stomatin, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, elliptocytosis 1, glycogen storage disease due to aldolase A deficiency, primary CD59 deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

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

346 retrieved; paginated sample, class counts are floors:

149 uncertain significance, 73 likely pathogenic, 26 likely benign, 22 benign/likely benign, 20 pathogenic, 20 pathogenic/likely pathogenic, 20 conflicting classifications of pathogenicity, 15 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028157	NM_001386140.1(MTTP):c.2578G>T (p.Glu860Ter)	MTTP	Pathogenic	criteria provided, single submitter
1068931	NM_001386140.1(MTTP):c.1949del (p.Ile650fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069126	NM_001386140.1(MTTP):c.1352_1355del (p.Val451fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072850	NM_001386140.1(MTTP):c.419dup (p.Asn140fs)	MTTP	Pathogenic	criteria provided, multiple submitters, no conflicts
1073794	NM_001386140.1(MTTP):c.373del (p.Leu125fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075423	NM_001386140.1(MTTP):c.141del (p.Gly49fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323301	NM_001386140.1(MTTP):c.501+1G>A	MTTP	Pathogenic	criteria provided, single submitter
1385779	NM_001386140.1(MTTP):c.1636_1637dup (p.Ile547fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1409778	NM_001386140.1(MTTP):c.2031del (p.Thr678fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14234	NM_001386140.1(MTTP):c.215del (p.Pro72fs)	MTTP	Pathogenic	criteria provided, single submitter
14235	NM_001386140.1(MTTP):c.1783C>T (p.Arg595Ter)	MTTP	Pathogenic	criteria provided, multiple submitters, no conflicts
14236	NM_001386140.1(MTTP):c.1867+5G>A	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14237	NM_001386140.1(MTTP):c.1237-1G>A	MTTP	Pathogenic	no assertion criteria provided
14238	NM_001386140.1(MTTP):c.1619G>A (p.Arg540His)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14239	NM_001386140.1(MTTP):c.1237_1344del (p.Ser413_Lys448del)	MTTP	Pathogenic	no assertion criteria provided
14240	NM_001386140.1(MTTP):c.2338A>T (p.Asn780Tyr)	MTTP	Pathogenic	no assertion criteria provided
14241	NM_001386140.1(MTTP):c.1769G>T (p.Ser590Ile)	MTTP	Pathogenic	no assertion criteria provided
14243	NM_001386140.1(MTTP):c.2593G>T (p.Gly865Ter)	MTTP	Pathogenic	criteria provided, multiple submitters, no conflicts
1687508	NM_001386140.1(MTTP):c.640del (p.Ala214fs)	MTTP	Pathogenic	criteria provided, single submitter
1726461	NM_001386140.1(MTTP):c.2228T>A (p.Leu743Ter)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1898960	NM_001386140.1(MTTP):c.672del (p.Asp224fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2107362	NM_001386140.1(MTTP):c.415C>T (p.Gln139Ter)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431640	NC_000004.12:g.(99601399_99613000)del	MTTP	Pathogenic	criteria provided, single submitter
2445867	NM_001386140.1(MTTP):c.2342+1G>A	MTTP	Pathogenic	criteria provided, multiple submitters, no conflicts
2690280	NM_001386140.1(MTTP):c.730C>T (p.Gln244Ter)	MTTP	Pathogenic	criteria provided, single submitter
2871245	NM_001386140.1(MTTP):c.2351_2352del (p.Val784fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2999044	NM_001386140.1(MTTP):c.1197del (p.Phe399fs)	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4058040	NM_001386140.1(MTTP):c.2218-1G>A	MTTP	Pathogenic	criteria provided, single submitter
4058049	NM_001386140.1(MTTP):c.1769+1G>A	MTTP	Pathogenic	criteria provided, single submitter
4081742	NM_001386140.1(MTTP):c.1769+2T>C	MTTP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
MTTP	Definitive	Autosomal recessive	abetalipoproteinemia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MTTP	Orphanet:14	Abetalipoproteinemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MTTP	HGNC:7467	ENSG00000138823	P55157	Microsomal triglyceride transfer protein large subunit	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MTTP	Microsomal triglyceride transfer protein large subunit	Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MTTP	Other/Unknown	no		Vitellogenin_N, Lipovitellin_superhlx_dom, Vitellinogen_b-sht_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
ileum	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MTTP	162	broad	marker	jejunal mucosa, ileal mucosa, ileum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MTTP	1,437

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MTTP	P55157	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 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
VLDL assembly	1	2284.0×	0.002	MTTP
LDL remodeling	1	1903.3×	0.002	MTTP
Chylomicron assembly	1	1142.0×	0.002	MTTP
Plasma lipoprotein assembly	1	713.8×	0.002	MTTP
Plasma lipoprotein remodeling	1	475.8×	0.003	MTTP
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.005	MTTP
Transport of small molecules	1	25.1×	0.040	MTTP

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
plasma lipoprotein particle assembly	1	16852.0×	9e-04	MTTP
triglyceride transport	1	4213.0×	0.001	MTTP
chylomicron assembly	1	4213.0×	0.001	MTTP
very-low-density lipoprotein particle assembly	1	1203.7×	0.002	MTTP
low-density lipoprotein particle remodeling	1	1053.2×	0.002	MTTP
lipoprotein transport	1	991.3×	0.002	MTTP
lipoprotein metabolic process	1	936.2×	0.002	MTTP
phospholipid transport	1	702.2×	0.003	MTTP
triglyceride metabolic process	1	443.5×	0.004	MTTP
response to calcium ion	1	318.0×	0.005	MTTP
protein secretion	1	263.3×	0.005	MTTP
circadian rhythm	1	244.2×	0.005	MTTP
establishment of localization in cell	1	160.5×	0.007	MTTP
cholesterol homeostasis	1	156.0×	0.007	MTTP
lipid metabolic process	1	91.6×	0.011	MTTP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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.

Symbol	Example approved molecule
MTTP	LOMITAPIDE MESYLATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MTTP	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LOMITAPIDE MESYLATE	4	MTTP
LOMITAPIDE	4	MTTP
DIRLOTAPIDE	2	MTTP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MTTP	19	Binding:15, Functional:4

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

3 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.

Compound	Max phase	Cohort target (bioactivity)
LOMITAPIDE MESYLATE	4	MTTP
LOMITAPIDE	4	MTTP
DIRLOTAPIDE	2	MTTP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MTTP
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT00004574	Not specified	COMPLETED	Vitamin Replacement in Abetalipoproteinemia
NCT05208879	Not specified	COMPLETED	CArotenoid in hypoChOlesterolemia