SCP2

Chr 1AR

sterol carrier protein 2

Also known as: NLTP, NSL-TP, SCOX, SCP-2, SCP-CHI, SCP-X, SCPX, nsLTP

NCBI Gene: 6342 ENSG00000116171 UniProt: Q9BX26 OMIM: 184755

This gene encodes sterol carrier protein X (SCPx), a peroxisome-associated thiolase involved in branched chain fatty acid oxidation, and sterol carrier protein 2 (SCP2), an intracellular lipid transfer protein. Mutations cause leukoencephalopathy with dystonia and motor neuropathy with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.76) and is highly expressed in organs involved in lipid metabolism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms.[provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.761 OMIM phenotype

Clinical Summary— SCP2

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Gene-Disease Validity (ClinGen)

sterol carrier protein 2 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 unique Pathogenic / Likely Pathogenic· 196 VUS of 539 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 2.59

OE 0.49 (0.33–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.26Z-score

OE missense 0.79 (0.71–0.88)

226 obs / 286.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.33–0.76)

0≤0.351.4

Missense OE?0.79 (0.71–0.88)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 15 / 30.4Missense obs/exp: 226 / 286.2Syn Z: 0.24

This gene — mechanism propensity

0.7033th %ile

GOF

0.6834th %ile

LOF

0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

539 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic12

VUS196

Likely Benign238

Benign44

Conflicting14

Pathogenic

Likely Pathogenic

196

VUS

238

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	0	3	0	19
Likely Pathogenic	10	0	2	0	12
VUS	3	177	14	2	196
Likely Benign	0	3	141	94	238
Benign	0	0	42	2	44
Conflicting	—				14
Total	29	180	202	98	523

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap SCP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →