SCP2

Summary

SCP2 (sterol carrier protein 2, HGNC:10606) is a protein-coding gene on chromosome 1p32.3, encoding Sterol carrier protein 2 (P22307). Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids.

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.

Source: NCBI Gene 6342 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sterol carrier protein 2 deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 532 total — 19 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_002979

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10606
Approved symbol	SCP2
Name	sterol carrier protein 2
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	nsLTP, SCPx, SCP-X
Ensembl gene	ENSG00000116171
Ensembl biotype	protein_coding
OMIM	184755
Entrez	6342

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000371509, ENST00000371513, ENST00000371514, ENST00000407246, ENST00000408941, ENST00000430330, ENST00000435345, ENST00000473584, ENST00000478274, ENST00000478631, ENST00000484100, ENST00000488965, ENST00000528311, ENST00000528809, ENST00000529363, ENST00000533119, ENST00000862565, ENST00000862566, ENST00000862567, ENST00000862568, ENST00000862569, ENST00000960962

RefSeq mRNA: 9 — MANE Select: NM_002979 NM_001007098, NM_001007099, NM_001007100, NM_001007250, NM_001193599, NM_001193600, NM_001193617, NM_001330587, NM_002979

CCDS: CCDS30719, CCDS41338, CCDS44149, CCDS44150, CCDS53317, CCDS53318, CCDS53319, CCDS572, CCDS81325

Canonical transcript exons

ENST00000371514 — 16 exons

Exon	Start	End
ENSE00002148975	52988029	52988136
ENSE00002152663	52927276	52927465
ENSE00002199588	53050609	53051698
ENSE00003468321	52950755	52950886
ENSE00003476279	52948009	52948080
ENSE00003489518	53047858	53047937
ENSE00003496485	52954740	52954804
ENSE00003586757	52961503	52961629
ENSE00003589639	53038917	53039046
ENSE00003621770	53014890	53015043
ENSE00003630674	52978217	52978367
ENSE00003636405	52976683	52976769
ENSE00003667249	52974769	52974832
ENSE00003669237	52941796	52941853
ENSE00003669844	53027969	53028071
ENSE00003680636	52980396	52980543

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 108.8292 / max 3545.5673, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2902	75.0797	1818
2899	21.6462	1758
2901	7.2585	1597
2900	4.8448	987

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.63	gold quality
esophagus squamous epithelium	UBERON:0006920	99.50	gold quality
right lobe of liver	UBERON:0001114	99.39	gold quality
palpebral conjunctiva	UBERON:0001812	99.38	gold quality
germinal epithelium of ovary	UBERON:0001304	99.34	gold quality
duodenum	UBERON:0002114	99.26	gold quality
rectum	UBERON:0001052	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.15	gold quality
colonic mucosa	UBERON:0000317	99.14	gold quality
jejunum	UBERON:0002115	99.09	gold quality
liver	UBERON:0002107	99.08	gold quality
gall bladder	UBERON:0002110	98.82	gold quality
epithelium of esophagus	UBERON:0001976	98.69	gold quality
pylorus	UBERON:0001166	98.68	gold quality
islet of Langerhans	UBERON:0000006	98.65	gold quality
gingival epithelium	UBERON:0001949	98.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.63	gold quality
oral cavity	UBERON:0000167	98.61	gold quality
colonic epithelium	UBERON:0000397	98.60	gold quality
gingiva	UBERON:0001828	98.59	gold quality
nephron tubule	UBERON:0001231	98.55	gold quality
renal medulla	UBERON:0000362	98.50	gold quality
nasal cavity mucosa	UBERON:0001826	98.45	gold quality
parietal pleura	UBERON:0002400	98.40	gold quality
mucosa of transverse colon	UBERON:0004991	98.39	gold quality
squamous epithelium	UBERON:0006914	98.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.36	gold quality
superior surface of tongue	UBERON:0007371	98.36	gold quality
upper leg skin	UBERON:0004262	98.34	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	14.79
E-HCAD-13	yes	13.06
E-MTAB-7249	no	1476.14
E-CURD-10	no	761.48
E-MTAB-10855	no	576.82
E-HCAD-31	no	2.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting SCP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-543	99.52	69.03	2595

Literature-anchored findings (GeneRIF, showing 17)

• data for the first time showed that while the N-terminal membrane binding domain of SCP(2) was itself inactive in mediating intermembrane sterol transfer, it nevertheless potentiated the ability of SCP(2) to enhance sterol transfer (PMID:12356316)
• plays a hitherto unrecognized role in intracellular phosphatidylinositol transfer, distribution, and signaling (PMID:12641450)
• SCP2 in the cellular defense against oxidative damage and found that a fluorescent fatty acid analog bound to SCP2 is protected against H2O2/Cu2+-induced oxidative damage (PMID:14563822)
• Overexpression of human SCP-2 in murine fibroblasts significantly alters the sterol dynamics of caveolae/lipid rafts, but not nonlipid raft domains, to facilitate retention of cholesterol within the cell. (PMID:14661971)
• By trafficking cholesterol hydroperoxides and phospholipid hydroperoxides in addition to parent lipids, SCP2 may exacerbate cell injury under oxidative stress conditions (PMID:15449949)
• Long chain fatty acyl-coenzyme A (CoA)s are confirmed to be high affinity ligands for SCP2, while long chain fatty acyl-carnitines are demonstrated for the first time not to interact with SCP2. (PMID:17418802)
• the importance of the N-terminal presequence in regulating SCP-2 structure, cholesterol localization within the ligand binding site, membrane association, and, potentially, intracellular targeting (PMID:18465878)
• Results describe the dynamical effect of sterol carrier protein-2 (SCP-2) interacting between aqueous dispersions of dehydroergosterol monohydrate microcrystal donors and acceptors. (PMID:19020914)
• cellular SCP-2 not only binds and translocates cholesterol but also cholesterol hydroperoxides, thus expanding their redox toxicity and signaling ranges under oxidative stress conditions (PMID:20656919)
• Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy. (PMID:20677014)
• The Peroxisomal targeting signal 1 in Scp2 is autonomous and is essential for binding to pex5. (PMID:21375735)
• We conclude that SCP-2 is a low affinity binding protein for arachidonylethanolamine that can facilitate its cellular uptake but does not contribute significantly to intracellular sequestration of AEA. (PMID:24510313)
• Mice harboring a deletion of the Scp2 locus present a modulated diurnal accumulation of lipids in the liver and a perturbed activation of several signaling pathways including PPARalpha, SREBP, LRH-1, TORC1 and its upstream regulators. (PMID:27097688)
• imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. (PMID:27311714)
• We (1) analyzed the structural basis of the fold and the classification of SCP2 domains; (2) identified structure-determined sequence features; (3) compared the lipid binding cavity of SCP2 and other lipid binding proteins; (4) surveyed proposed mechanisms of SCP2 mediated lipid transfer between membranes; and (5) uncovered a possible new function of the SCP2 domain as a protein-protein recognition device. (PMID:28284963)
• Methylation dependent microRNA 1285-5p and sterol carrier proteins 2 in type 2 diabetes mellitus (PMID:31407919)
• LINC00261 elevation inhibits angiogenesis and cell cycle progression of pancreatic cancer cells by upregulating SCP2 via targeting FOXP3. (PMID:34541823)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	scp2b	ENSDARG00000102356
mus_musculus	Scp2	ENSMUSG00000028603
drosophila_melanogaster	ScpX	FBGN0015808

Paralogs (1): SCP2D1 (ENSG00000132631)

Protein

Protein identifiers

Sterol carrier protein 2 — P22307 (reviewed: P22307)

Alternative names: Acetyl-CoA C-myristoyltransferase, Non-specific lipid-transfer protein, Propanoyl-CoA C-acyltransferase, SCP-2/3-oxoacyl-CoA thiolase, SCP-2/thiolase, SCP-chi, SCPX, Sterol carrier protein X

All UniProt accessions (7): P22307, A0A384NY87, E9PLD1, H0YCB0, H0YD06, H0YEU8, H0YF61

UniProt curated annotations — full annotation on UniProt →

Function. Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids. Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs. Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol. Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs.

Subunit / interactions. Interacts with PEX5; the interaction is essential for peroxisomal import.

Subcellular location. Peroxisome. Cytoplasm. Mitochondrion. Endoplasmic reticulum. Mitochondrion Peroxisome.

Tissue specificity. Liver, fibroblasts, and placenta.

Post-translational modifications. preSCP2, a protein with a molecular mass of about 15 kDa, is processed into its mature form (SCP2) by proteolytic cleavage of a 20 residue leader sequence after translocation into peroxisomes.

Disease relevance. Leukoencephalopathy with dystonia and motor neuropathy (LKDMN) [MIM:613724] A syndrome characterized by leukoencephalopathy, dystonic head tremor, spasmodic torticollis and reduced tendon reflexes in lower extremities. Additional features include hyposmia, pathologic saccadic eye movements, a slight hypoacusis, accumulation of branched-chain pristanic acid in plasma, and the presence of abnormal bile alcohol glucuronides in urine. The disease is caused by variants affecting the gene represented in this entry. Expression at protein level is almost abolished in Zellweger syndrome. Cholesterol transfer from the endoplasmic reticulum to the plasma membrane was reduced in patient fibroblasts compared to controls.

Induction. Up-regulated by 4-hydroxy-tamoxifen.

Miscellaneous. Contains a putative mitochondrial transit peptide at positions 1-20. Produced by alternative splicing. Produced by alternative splicing. Produced by alternative splicing.

Similarity. In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.

Isoforms (8)

UniProt ID	Names	Canonical?
P22307-1	SCPx	yes
P22307-2	SCP2
P22307-3	3
P22307-4	4
P22307-5	5
P22307-6	6
P22307-7	7
P22307-8	8

RefSeq proteins (9): NP_001007099, NP_001007100, NP_001007101, NP_001007251, NP_001180528, NP_001180529, NP_001180546, NP_001317516, NP_002970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003033	SCP2_sterol-bd_dom	Domain
IPR016039	Thiolase-like	Homologous_superfamily
IPR020613	Thiolase_CS	Conserved_site
IPR020615	Thiolase_acyl_enz_int_AS	Active_site
IPR020616	Thiolase_N	Domain
IPR036527	SCP2_sterol-bd_dom_sf	Homologous_superfamily
IPR055140	Thiolase_C_2	Domain

Pfam: PF00108, PF02036, PF22691

Enzyme classification (BRENDA):

• EC 2.3.1.176 — propanoyl-CoA C-acyltransferase (BRENDA: 12 organisms, 3 substrates, 6 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 12 shown:

• 4,8,12-trimethyltridecanoyl-CoA + propanoyl-CoA = 3-oxopristanoyl-CoA + CoA (RHEA:10408)
• choloyl-CoA + propanoyl-CoA = 3alpha,7alpha,12alpha-trihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA + CoA (RHEA:16865)
• tetradecanoyl-CoA + acetyl-CoA = 3-oxohexadecanoyl-CoA + CoA (RHEA:18161)
• an acyl-CoA + acetyl-CoA = a 3-oxoacyl-CoA + CoA (RHEA:21564)
• octanoyl-CoA + acetyl-CoA = 3-oxodecanoyl-CoA + CoA (RHEA:31087)
• dodecanoyl-CoA + acetyl-CoA = 3-oxotetradecanoyl-CoA + CoA (RHEA:31091)
• butanoyl-CoA + acetyl-CoA = 3-oxohexanoyl-CoA + CoA (RHEA:31111)
• decanoyl-CoA + acetyl-CoA = 3-oxododecanoyl-CoA + CoA (RHEA:31183)
• hexanoyl-CoA + acetyl-CoA = 3-oxooctanoyl-CoA + CoA (RHEA:31203)
• hexadecanoyl-CoA + acetyl-CoA = 3-oxooctadecanoyl-CoA + CoA (RHEA:35279)
• 3-oxohexadecanedioyl-CoA + CoA = tetradecanedioyl-CoA + acetyl-CoA (RHEA:40343)
• propanoyl-CoA + tetradecanoyl-CoA = 3-oxo-2-methylhexadecanoyl-CoA + CoA (RHEA:46344)

UniProt features (67 total): modified residue 29, sequence conflict 9, splice variant 8, helix 6, strand 5, mutagenesis site 3, turn 2, chain 1, domain 1, short sequence motif 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2C0L	X-RAY DIFFRACTION	2.3
1QND	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22307-F1	92.39	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 20–21 (cleavage)

Post-translational modifications (29): 183, 282, 341, 341, 432, 432, 438, 438, 443, 443, 453, 453, 464, 470, 470, 479, 491, 492, 511, 516 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
528	strongly reduces sterol carrier and phosphatidylcholine transfer activity; when associated with d-530.
528	strongly reduces sterol carrier and phosphatidylcholine transfer activity.
530	strongly reduces sterol carrier and phosphatidylcholine transfer activity; when associated with d-528.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-9033241	Peroxisomal protein import
R-HSA-9033500	TYSND1 cleaves peroxisomal proteins
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-389887	Beta-oxidation of pristanoyl-CoA
R-HSA-1430728	Metabolism
R-HSA-2046104	alpha-linolenic (omega3) and linoleic (omega6) acid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9609507	Protein localization

MSigDB gene sets: 413 (showing top): GOBP_LIPID_MODIFICATION, MODULE_52, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS

GO Biological Process (23): fatty acid beta-oxidation (GO:0006635), unsaturated fatty acid biosynthetic process (GO:0006636), steroid biosynthetic process (GO:0006694), bile acid biosynthetic process (GO:0006699), progesterone biosynthetic process (GO:0006701), bile acid metabolic process (GO:0008206), phospholipid transport (GO:0015914), regulation of lipid metabolic process (GO:0019216), intracellular cholesterol transport (GO:0032367), positive regulation of intracellular cholesterol transport (GO:0032385), inositol trisphosphate biosynthetic process (GO:0032959), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), alpha-linolenic acid metabolic process (GO:0036109), long-chain fatty acid biosynthetic process (GO:0042759), positive regulation of steroid metabolic process (GO:0045940), regulation of phospholipid biosynthetic process (GO:0071071), protein localization to plasma membrane (GO:0072659), lipid hydroperoxide transport (GO:1901373), fatty acid derivative biosynthetic process (GO:1901570), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), sterol transport (GO:0015918), intermembrane lipid transfer (GO:0120009)

GO Molecular Function (17): fatty-acyl-CoA binding (GO:0000062), acetyl-CoA C-acyltransferase activity (GO:0003988), signaling receptor binding (GO:0005102), phosphatidylinositol transfer activity (GO:0008526), cholesterol binding (GO:0015485), propanoyl-CoA C-acyltransferase activity (GO:0033814), long-chain fatty acyl-CoA binding (GO:0036042), propionyl-CoA C2-trimethyltridecanoyltransferase activity (GO:0050632), acetyl-CoA C-myristoyltransferase activity (GO:0050633), oleic acid binding (GO:0070538), phosphatidylcholine transfer activity (GO:0120019), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515), lipid binding (GO:0008289), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1
Protein localization	1
Peroxisomal protein import	1
Synthesis of bile acids and bile salts	1
Peroxisomal lipid metabolism	1
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
steroid metabolic process	3
acyltransferase activity, transferring groups other than amino-acyl groups	3
cytoplasm	3
fatty acid biosynthetic process	2
unsaturated fatty acid metabolic process	2
lipid biosynthetic process	2
lipid transport	2
intracellular anatomical structure	2
long-chain fatty acid metabolic process	2
binding	2
intracellular membrane-bounded organelle	2
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
C21-steroid hormone biosynthetic process	1
ketone biosynthetic process	1
progesterone metabolic process	1
olefinic compound biosynthetic process	1
monocarboxylic acid metabolic process	1
organophosphate ester transport	1
lipid metabolic process	1
regulation of primary metabolic process	1
cholesterol transport	1
intracellular sterol transport	1
intracellular cholesterol transport	1
positive regulation of cholesterol transport	1
positive regulation of intracellular sterol transport	1
regulation of intracellular cholesterol transport	1
inositol trisphosphate metabolic process	1
inositol phosphate biosynthetic process	1
fatty acid beta-oxidation	1
olefinic compound metabolic process	1
regulation of steroid metabolic process	1
positive regulation of lipid metabolic process	1
phospholipid biosynthetic process	1
regulation of lipid biosynthetic process	1
regulation of phospholipid metabolic process	1

Protein interactions and networks

STRING

2180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCP2	FDX1	P10109	900
SCP2	FDXR	P22570	796
SCP2	PEX5	P50542	776
SCP2	STAR	P49675	767
SCP2	TECR	Q9NZ01	765
SCP2	DBI	P07108	756
SCP2	ACOX1	Q15067	715
SCP2	ACOX2	Q99424	691
SCP2	CAV1	Q03135	683
SCP2	CYP11A1	P05108	641
SCP2	ACOX3	O15254	627
SCP2	ABCD3	P28288	623
SCP2	AMACR	Q9UHK6	616
SCP2	EHHADH	Q08426	613
SCP2	FABP1	P07148	606

IntAct

50 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
HRAS	MTHFD2	psi-mi:“MI:0914”(association)	0.730
SCP2	TRIP13	psi-mi:“MI:0915”(physical association)	0.670
TRIP13	SCP2	psi-mi:“MI:0915”(physical association)	0.670
Cav1	SCP2	psi-mi:“MI:0403”(colocalization)	0.460
SCP2	Cav1	psi-mi:“MI:0915”(physical association)	0.460
Cav1	SCP2	psi-mi:“MI:0915”(physical association)	0.460
CAV1	SCP2	psi-mi:“MI:2364”(proximity)	0.450
SCP2	CAV1	psi-mi:“MI:0915”(physical association)	0.450
CAV1	SCP2	psi-mi:“MI:0915”(physical association)	0.450
SCP2	HSD17B4	psi-mi:“MI:0915”(physical association)	0.400
URB2	SCP2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SCP2		psi-mi:“MI:0915”(physical association)	0.370
SCP2	CREB3	psi-mi:“MI:0915”(physical association)	0.370
CACNA1A	SCP2	psi-mi:“MI:0915”(physical association)	0.370
	SCP2	psi-mi:“MI:0915”(physical association)	0.370
CREB3	SCP2	psi-mi:“MI:0915”(physical association)	0.370
PDHA1		psi-mi:“MI:0914”(association)	0.350
	SCP2	psi-mi:“MI:0914”(association)	0.350
ITSN1	AP2A2	psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CEP63	CIT	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
TYSND1	ECI2	psi-mi:“MI:0914”(association)	0.350
TYSND1	SCP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): TRIP13 (Two-hybrid), MYO5A (Affinity Capture-MS), MYO5C (Affinity Capture-MS), POLR1A (Affinity Capture-MS), URI1 (Affinity Capture-MS), PDRG1 (Affinity Capture-MS), UXT (Affinity Capture-MS), SCP2 (Co-fractionation), SCP2 (Affinity Capture-MS), SCP2 (Two-hybrid), TRIP13 (Two-hybrid), MYO5C (Affinity Capture-MS), URI1 (Affinity Capture-MS), MYO5A (Affinity Capture-MS), SCP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A075TJ05, A0A0F7U103, A0A161CEU9, A0A193PS74, A0A1E1FFN8, A0A1Y0BRF1, A0A2I1BSV9, A0A455R5P9, A0A5C1RD96, A0A8F4SKJ7, A2QTE9, A2R2V4, A6NK06, A6QP15, B3FWS8, B3IUN8, B6HV32, B6QK81, B8MKZ4, D7RJN6, G0R6S9, G3XMC4, G3XP38, H8F0D6, P22307, P54956, P54987, P9WET2, Q01N44, Q08B39, Q0C8A4, Q0C8L3, Q0JFH7, Q17EN4, Q28XT3, Q2TXG0, Q2U852, Q4QQW3, Q4WMJ5, Q5BBP8

Diamond homologs: A0A384E138, G5EDP2, O26884, O62742, P07857, P11915, P22307, P27796, P32020, Q07598, Q39VG1, Q58944, Q7MQI0, Q87TP0, Q8DDK5, Q9KJF3, A0A097ZPE8, A0A144Y7G4, A0A162J3X8, A0A1L5BU05, A0A1V0QSC6, A0A2H3D8Y2, A0R518, A3LZU7, A4FUZ6, A6SSW9, C1DMX5, D4Z260, F1QWW8, M2ZIX7, O75911, O77769, O86034, O88876, P0A2D1, P0A2D2, P0AET8, P0AET9, P0CU75, P0DX40

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TYSND1	“up-regulates activity”	SCP2	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	6	32.4×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

532 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	9
Uncertain significance	196
Likely benign	230
Benign	42

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1033966	NM_002979.5(SCP2):c.1111C>T (p.Gln371Ter)	Pathogenic
12810	NM_002979.5(SCP2):c.550dup (p.Ile184fs)	Pathogenic
1374591	NM_002979.5(SCP2):c.103_125dup (p.Gly43fs)	Pathogenic
1375705	NM_002979.5(SCP2):c.325C>T (p.Gln109Ter)	Pathogenic
1400862	NM_002979.5(SCP2):c.838dup (p.Met280fs)	Pathogenic
1451680	NM_002979.5(SCP2):c.481C>T (p.Gln161Ter)	Pathogenic
1992758	NM_002979.5(SCP2):c.683C>G (p.Ser228Ter)	Pathogenic
2007648	NM_002979.5(SCP2):c.313dup (p.Arg105fs)	Pathogenic
2035627	NM_002979.5(SCP2):c.417del (p.Thr140fs)	Pathogenic
2045377	NM_002979.5(SCP2):c.1170dup (p.Asn391Ter)	Pathogenic
2059273	NM_002979.5(SCP2):c.229_232del (p.Tyr77fs)	Pathogenic
2424590	NC_000001.10:g.(?53407448)(53407545_?)del	Pathogenic
2424591	NC_000001.10:g.(?53407448)(53446235_?)del	Pathogenic
2696338	NM_002979.5(SCP2):c.535G>T (p.Glu179Ter)	Pathogenic
2761715	NM_002979.5(SCP2):c.151C>T (p.Gln51Ter)	Pathogenic
3247943	NC_000001.10:g.(?53420392)(53420496_?)del	Pathogenic
3666471	NM_002979.5(SCP2):c.739dup (p.Leu247fs)	Pathogenic
3895897	NM_002979.5(SCP2):c.617del (p.Ser205_Leu206insTer)	Pathogenic
4712707	NM_002979.5(SCP2):c.1135_1136dup (p.Gln380fs)	Pathogenic
1953544	NM_002979.5(SCP2):c.675-1G>C	Likely pathogenic
2155314	NM_002979.5(SCP2):c.127+2T>C	Likely pathogenic
2783349	NM_002979.5(SCP2):c.1236-1G>T	Likely pathogenic
2836448	NM_002979.5(SCP2):c.974-1G>C	Likely pathogenic
2870848	NM_002979.5(SCP2):c.825+1G>A	Likely pathogenic
3247944	NC_000001.10:g.(?53427155)(53427321_?)dup	Likely pathogenic
3362520	NM_002979.5(SCP2):c.973+1G>A	Likely pathogenic
3632636	NM_002979.5(SCP2):c.524-2A>G	Likely pathogenic
3673663	NM_002979.5(SCP2):c.199+1G>A	Likely pathogenic

SpliceAI

3164 predictions. Top by Δscore:

Variant	Effect	Δscore
1:52941794:A:AG	acceptor_gain	1.0000
1:52941795:G:GC	acceptor_gain	1.0000
1:52941795:GTTT:G	acceptor_gain	1.0000
1:52947729:GCT:G	donor_gain	1.0000
1:52950882:GGGTG:G	donor_gain	1.0000
1:52950883:GGTGG:G	donor_gain	1.0000
1:52950884:G:T	donor_gain	1.0000
1:52950884:GTG:G	donor_gain	1.0000
1:52974833:G:GG	donor_gain	1.0000
1:52976678:TTTA:T	acceptor_loss	1.0000
1:52976681:A:T	acceptor_loss	1.0000
1:52976682:G:GT	acceptor_loss	1.0000
1:52976735:G:GT	donor_gain	1.0000
1:52976765:TGTTG:T	donor_loss	1.0000
1:52976766:GTTG:G	donor_gain	1.0000
1:52976767:TTGG:T	donor_loss	1.0000
1:52976771:T:G	donor_loss	1.0000
1:52978215:A:AG	acceptor_gain	1.0000
1:52978216:G:GG	acceptor_gain	1.0000
1:52980539:AGAAG:A	donor_loss	1.0000
1:52980540:GAAG:G	donor_gain	1.0000
1:52980541:AAG:A	donor_loss	1.0000
1:52980542:AGGTA:A	donor_loss	1.0000
1:52980543:GGTA:G	donor_loss	1.0000
1:52980544:G:T	donor_loss	1.0000
1:52980545:T:G	donor_loss	1.0000
1:52988024:TATA:T	acceptor_loss	1.0000
1:52988026:TA:T	acceptor_loss	1.0000
1:52988027:A:AT	acceptor_loss	1.0000
1:52988132:TACAG:T	donor_loss	1.0000

AlphaMissense

3607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:52980486:G:C	D306H	0.997
1:52988098:G:A	G348D	0.997
1:52988104:T:C	L350P	0.997
1:52988120:C:A	H355Q	0.997
1:52988120:C:G	H355Q	0.997
1:52980487:A:T	D306V	0.996
1:52980492:T:C	F308L	0.996
1:52980494:T:A	F308L	0.996
1:52980494:T:G	F308L	0.996
1:52988090:T:A	N345K	0.996
1:52988090:T:G	N345K	0.996
1:52988115:G:A	G354R	0.996
1:52988115:G:C	G354R	0.996
1:52988116:G:A	G354E	0.996
1:52988118:C:G	H355D	0.996
1:52988119:A:G	H355R	0.996
1:52950831:T:A	N92K	0.995
1:52950831:T:G	N92K	0.995
1:52980483:C:G	H305D	0.995
1:52980491:C:G	C307W	0.995
1:52988094:A:C	S347R	0.995
1:52988096:T:A	S347R	0.995
1:52988096:T:G	S347R	0.995
1:52988098:G:T	G348V	0.995
1:53014981:T:A	N391K	0.995
1:53014981:T:G	N391K	0.995
1:52954766:G:T	G120W	0.994
1:52974830:C:A	N195K	0.994
1:52974830:C:G	N195K	0.994
1:52941796:T:C	F24L	0.993

dbSNP variants (sampled 300 via entrez): RS1000012126 (1:53030063 A>G), RS1000102129 (1:52943637 T>C), RS1000122791 (1:52958551 T>A), RS1000192784 (1:52991383 C>T), RS1000211743 (1:53030414 C>T), RS1000230195 (1:52936950 A>G), RS1000308717 (1:52987413 T>C), RS1000343631 (1:52931134 G>A), RS1000349778 (1:53017632 T>G), RS1000397542 (1:52930837 G>A,C), RS1000426407 (1:53024013 C>T), RS1000458389 (1:52963860 A>G), RS1000555152 (1:52968350 A>G), RS1000588782 (1:53001875 T>C), RS1000632276 (1:53005151 G>A)

Disease associations

OMIM: gene MIM:184755 | disease phenotypes: MIM:613724, MIM:312080

GenCC curated gene-disease

Disease	Classification	Inheritance
sterol carrier protein 2 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
sterol carrier protein 2 deficiency	Definitive	AR

Mondo (3): sterol carrier protein 2 deficiency (MONDO:0013391), leukodystrophy (MONDO:0019046), sensorineural hearing loss disorder (MONDO:0020678)

Orphanet (2): Leukoencephalopathy-dystonia-motor neuropathy syndrome (Orphanet:163684), Leukodystrophy (Orphanet:68356)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5950 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.47	Kd	339	nM	CHEMBL260520
6.02	Kd	947	nM	CHEMBL260520

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[9-(diethylamino)-5-oxobenzo[a]phenoxazin-2-yl]oxybutanoic acid	323980: Binding affinity to site 1 of human mature SCP2	kd	0.3390	uM

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
Acetaminophen	decreases expression, affects cotreatment	3
Cyclosporine	decreases expression, affects cotreatment	3
sodium arsenite	decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, decreases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
kojic acid	decreases expression	1
terbufos	decreases methylation	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
pentanal	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4232646	Binding	Binding affinity to SCP2 cysteine residue in human 786-O cell soluble proteomic lysate at 5 uM incubated for 1 hr followed by cell lysis by IA-alkyne probe based isoTOP-ABPP analysis	Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

98 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
NCT00889174	Not specified	COMPLETED	The Nosology and Etiology of Leukodystrophies of Unknown Causes
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02843555	Not specified	COMPLETED	Natural History of the Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT03639285	Not specified	RECRUITING	Natural History, Diagnosis, and Outcomes for Leukodystrophies
NCT05443906	Not specified	RECRUITING	Home Exercise for Individuals with Neurodegenerative Disease
NCT02693704	PHASE2/PHASE3	COMPLETED	Evaluation of a Binaural Spatialization Method for Hearing Aids
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01267994	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Anakinra for Steroid-Resistant Autoimmune Inner Ear Disease
NCT01902914	PHASE1/PHASE2	UNKNOWN	Effectiveness of P02 Digital Hearing Aids
NCT02038972	PHASE1/PHASE2	COMPLETED	Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss
NCT02616172	PHASE1/PHASE2	SUSPENDED	Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss
NCT03616223	PHASE1/PHASE2	COMPLETED	FX-322 in Sensorineural Hearing Loss
NCT04129775	PHASE1/PHASE2	COMPLETED	OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
NCT04462198	PHASE1/PHASE2	COMPLETED	Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss
NCT07032038	PHASE1/PHASE2	NOT_YET_RECRUITING	First In Human Randomised Trial of Rincell-1 in Adults With a Cochlear Implant
NCT06025097	EARLY_PHASE1	COMPLETED	Intra-Tympanic Steroid With PRP Combination in Sensorineural Hearing Loss and Tinnitus.
NCT06707389	EARLY_PHASE1	NOT_YET_RECRUITING	Autologous Blood Monocyte Vesicles for the Treatment of Sudden Deafness
NCT07472023	EARLY_PHASE1	ENROLLING_BY_INVITATION	Regenerative Medicine and Stem Cell-Based Interventions for Inner Ear Trauma, Tinnitus, and Sensorineural Hearing Loss
NCT00023036	Not specified	COMPLETED	Clinical and Genetic Analysis of Enlarged Vestibular Aqueducts
NCT00023049	Not specified	COMPLETED	Genetic Analysis of Hereditary Disorders of Hearing and Balance
NCT00261768	Not specified	COMPLETED	Efficacy of Digital Noise Reduction Strategies: A Hearing Aid Trial
NCT00589511	Not specified	COMPLETED	Nucleus Freedom Cochlear Implant System Pediatric Post-approval Study
NCT00678899	Not specified	COMPLETED	Evaluation of the Nucleus Hybrid™ L24 Cochlear Implant System
NCT00787189	Not specified	COMPLETED	Study of Low Level Laser Therapy and Word Recognition in Hearing Impaired Individuals
NCT01184248	Not specified	COMPLETED	The Effect of Sound Stimulation on Pure-tone Hearing Threshold
NCT01434446	Not specified	COMPLETED	The Effect of Sound Stimulation on Hearing Ability
NCT01749592	Not specified	COMPLETED	Single-sided Deafness and Cochlear Implants