Sterol carrier protein 2 deficiency

Summary

Sterol carrier protein 2 deficiency (MONDO:0013391) is a disease caused by SCP2 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SCP2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 13
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	sterol carrier protein 2 deficiency
Mondo ID	MONDO:0013391
OMIM	613724
Orphanet	163684
UMLS	C3150990
MedGen	462340
GARD	0012471
Is cancer (heuristic)	no

Also known as: leukoencephalopathy - dystonia - motor neuropathy · leukoencephalopathy-dystonia-motor neuropathy syndrome · LKDMN · SCP2 deficiency · sterol carrier protein 2 deficiency

Data availability: 13 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › sterol carrier protein 2 deficiency

Related subtypes (64): Alexander disease, cerebrotendinous xanthomatosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, dermatoleukodystrophy, Krabbe disease, Sjogren-Larsson syndrome, Canavan disease, Pelizaeus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, megalencephalic leukoencephalopathy with subcortical cysts, ribose-5-P isomerase deficiency, hypomyelinating leukodystrophy 5, leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome, hypomyelinating leukodystrophy 6, cystic leukoencephalopathy without megalencephaly, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, hypomyelination with brain stem and spinal cord involvement and leg spasticity, leukoencephalopathy with mild cerebellar ataxia and white matter edema, progressive encephalopathy with leukodystrophy due to DECR deficiency, hypomyelinating leukodystrophy 9, multiple mitochondrial dysfunctions syndrome 4, hypomyelinating leukodystrophy 10, hypomyelinating leukodystrophy 12, hypomyelinating leukodystrophy 13, leukoencephalopathy with bilateral anterior temporal lobe cysts, progressive cavitating leukoencephalopathy, Pelizaeus-Merzbacher-like disease, CADDS, adrenoleukodystrophy, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, Aicardi-Goutieres syndrome, metachromatic leukodystrophy, peroxisome biogenesis disorder, unknown leukodystrophy, ravine syndrome, leukodystrophy, hypomyelinating, 22, leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, leukodystrophy, hypomyelinating, 18, leukodystrophy, hypomyelinating, 19, transient infantile, spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, leukodystrophy, hypomyelinating, 14, leukodystrophy, hypomyelinating, 20, early-onset calcifying leukoencephalopathy-skeletal dysplasia, c11orf73-related autosomal recessive hypomyelinating leukodystrophy, alkaline ceramidase 3 deficiency, leukodystrophy, hypomyelinating, 15, leukodystrophy, hypomyelinating, 16, leukodystrophy, hypomyelinating, 17, POLR-related leukodystrophy, leukoencephalopathy, diffuse hereditary, with spheroids 1, leukoencephalopathy with vanishing white matter, leukodystrophy, hypomyelinating, 24, leukodystrophy, childhood-onset, remitting, leukodystrophy, hypomyelinating, 25, leukodystrophy, hypomyelinating, 26, with chondrodysplasia, adult-onset progressive leukoencephalopathy-early-onset deafness, leukoencephalopathy, porphyria-related, episodic memory defect leukoencephalopathy, leukodystrophy, hypomyelinating, 28, leukodystrophy, demyelinating, adult-onset, leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy, leukoencephalopathy without lacunae, adult-onset, AARS1-related leukoencephalopathy

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

13 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 2 pathogenic/likely pathogenic, 1 likely benign, 1 likely pathogenic, 1 not provided, 1 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033966	NM_002979.5(SCP2):c.1111C>T (p.Gln371Ter)	SCP2	Pathogenic	criteria provided, multiple submitters, no conflicts
12810	NM_002979.5(SCP2):c.550dup (p.Ile184fs)	SCP2	Pathogenic	criteria provided, single submitter
1911686	NM_002979.5(SCP2):c.588dup	SCP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3895897	NM_002979.5(SCP2):c.617del (p.Ser205_Leu206insTer)	SCP2	Pathogenic	criteria provided, single submitter
488590	NM_002979.5(SCP2):c.825+1G>T	SCP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3362520	NM_002979.5(SCP2):c.973+1G>A	SCP2	Likely pathogenic	criteria provided, single submitter
594561	NM_002979.5(SCP2):c.1234A>G (p.Ser412Gly)	SCP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1050589	NM_002979.5(SCP2):c.572A>G (p.His191Arg)	SCP2	Uncertain significance	criteria provided, single submitter
1512271	NM_002979.5(SCP2):c.230A>G (p.Tyr77Cys)	SCP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
977231	NM_002979.5(SCP2):c.886C>T (p.Pro296Ser)	SCP2	Uncertain significance	criteria provided, single submitter
1610163	NM_002979.5(SCP2):c.973+15T>G	SCP2	Likely benign	criteria provided, multiple submitters, no conflicts
801491	NM_002979.5(SCP2):c.70-47del	SCP2	Benign	criteria provided, multiple submitters, no conflicts
585030	NM_002979.5(SCP2):c.825G>T (p.Met275Ile)	SCP2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
CTDSP2	Strong	Autosomal recessive	sterol carrier protein 2 deficiency	3
SCP2	Strong	Autosomal recessive	sterol carrier protein 2 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCP2	Orphanet:163684	Leukoencephalopathy-dystonia-motor neuropathy syndrome

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
SCP2	HGNC:10606	ENSG00000116171	P22307	Sterol carrier protein 2	gencc,clinvar
CTDSP2	HGNC:17077	ENSG00000175215	O14595	Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCP2	Sterol carrier protein 2	Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids.
CTDSP2	Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2	Preferentially catalyzes the dephosphorylation of ‘Ser-5’ within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Phosphatase	1	42.0×	0.047
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCP2	Enzyme (other)	yes	2.3.1.176	SCP2_sterol-bd_dom, Thiolase-like, Thiolase_CS
CTDSP2	Phosphatase	yes		FCP1_dom, Dullard_phosphatase, HAD_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
esophagus squamous epithelium	1
jejunal mucosa	1
right lobe of liver	1
descending thoracic aorta	1
mucosa of stomach	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCP2	295	ubiquitous	marker	jejunal mucosa, esophagus squamous epithelium, right lobe of liver
CTDSP2	295	ubiquitous	marker	mucosa of stomach, stromal cell of endometrium, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCP2	2,320
CTDSP2	1,453

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCP2	P22307	2
CTDSP2	O14595	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	951.7×	0.006	SCP2
TYSND1 cleaves peroxisomal proteins	1	713.8×	0.006	SCP2
Beta-oxidation of pristanoyl-CoA	1	571.0×	0.006	SCP2
alpha-linolenic acid (ALA) metabolism	1	356.9×	0.008	SCP2
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	228.4×	0.010	SCP2
XBP1(S) activates chaperone genes	1	107.7×	0.016	CTDSP2
Protein localization	1	95.2×	0.016	SCP2
Peroxisomal protein import	1	86.5×	0.016	SCP2
Fatty acid metabolism	1	65.6×	0.019	SCP2
Metabolism of lipids	1	15.8×	0.069	SCP2
Metabolism	1	5.8×	0.165	SCP2

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
positive regulation of intracellular cholesterol transport	1	8426.0×	0.001	SCP2
positive regulation of steroid metabolic process	1	8426.0×	0.001	SCP2
regulation of phospholipid biosynthetic process	1	4213.0×	0.001	SCP2
lipid hydroperoxide transport	1	4213.0×	0.001	SCP2
inositol trisphosphate biosynthetic process	1	2808.7×	0.001	SCP2
progesterone biosynthetic process	1	1685.2×	0.002	SCP2
fatty acid derivative biosynthetic process	1	766.0×	0.004	SCP2
intracellular cholesterol transport	1	648.1×	0.004	SCP2
fatty acid beta-oxidation using acyl-CoA oxidase	1	561.7×	0.004	SCP2
bile acid metabolic process	1	495.6×	0.004	SCP2
alpha-linolenic acid metabolic process	1	443.5×	0.004	SCP2
phospholipid transport	1	351.1×	0.005	SCP2
unsaturated fatty acid biosynthetic process	1	324.1×	0.005	SCP2
bile acid biosynthetic process	1	312.1×	0.005	SCP2
steroid biosynthetic process	1	300.9×	0.005	SCP2
long-chain fatty acid biosynthetic process	1	221.7×	0.006	SCP2
regulation of lipid metabolic process	1	216.1×	0.006	SCP2
fatty acid beta-oxidation	1	187.2×	0.006	SCP2
negative regulation of G1/S transition of mitotic cell cycle	1	179.3×	0.006	CTDSP2
protein dephosphorylation	1	110.9×	0.009	CTDSP2
protein localization to plasma membrane	1	54.4×	0.018	SCP2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCP2	0	0
CTDSP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SCP2	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SCP2	2.3.1.176	propanoyl-CoA C-acyltransferase

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	2	SCP2, CTDSP2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
SCP2	4	—
CTDSP2	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
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)