SCP2

Chr 1AR

sterol carrier protein 2

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.761 OMIM phenotype
Clinical SummarySCP2
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Gene-Disease Validity (ClinGen)
sterol carrier protein 2 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.000
Z-score 2.59
OE 0.49 (0.330.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.26Z-score
OE missense 0.79 (0.710.88)
226 obs / 286.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.330.76)
00.351.4
Missense OE0.79 (0.710.88)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 15 / 30.4Missense obs/exp: 226 / 286.2Syn Z: 0.24
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SCP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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