CTDSP2

Summary

CTDSP2 (CTD small phosphatase 2, HGNC:17077) is a protein-coding gene on chromosome 12q14.1, encoding Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (O14595). 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.

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be part of TIM23 mitochondrial import inner membrane translocase complex.

Source: NCBI Gene 10106 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sterol carrier protein 2 deficiency (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 571 total — 19 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_005730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17077
Approved symbol	CTDSP2
Name	CTD small phosphatase 2
Location	12q14.1
Locus type	gene with protein product
Status	Approved
Aliases	OS4, SCP2, PSR2
Ensembl gene	ENSG00000175215
Ensembl biotype	protein_coding
OMIM	608711
Entrez	10106

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000398073, ENST00000547169, ENST00000547701, ENST00000548823, ENST00000549039, ENST00000550144, ENST00000551594, ENST00000552294

RefSeq mRNA: 1 — MANE Select: NM_005730 NM_005730

CCDS: CCDS41801

Canonical transcript exons

ENST00000398073 — 8 exons

Exon	Start	End
ENSE00001377388	57846372	57846729
ENSE00001531465	57819927	57823727
ENSE00003468626	57824227	57824319
ENSE00003557216	57826346	57826402
ENSE00003577817	57826996	57827097
ENSE00003582323	57829448	57829596
ENSE00003623007	57823904	57824089
ENSE00003694209	57827552	57827590

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.8356 / max 879.7749, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131768	69.5516	1820
131767	0.1548	53
131766	0.1292	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	98.24	gold quality
stromal cell of endometrium	CL:0002255	98.17	gold quality
descending thoracic aorta	UBERON:0002345	98.12	gold quality
body of uterus	UBERON:0009853	98.09	gold quality
left ovary	UBERON:0002119	98.08	gold quality
right coronary artery	UBERON:0001625	97.98	gold quality
right ovary	UBERON:0002118	97.96	gold quality
right lung	UBERON:0002167	97.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.90	gold quality
lower esophagus	UBERON:0013473	97.89	gold quality
ovary	UBERON:0000992	97.82	gold quality
left uterine tube	UBERON:0001303	97.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.77	gold quality
body of pancreas	UBERON:0001150	97.68	gold quality
cardia of stomach	UBERON:0001162	97.63	gold quality
popliteal artery	UBERON:0002250	97.61	gold quality
ventricular zone	UBERON:0003053	97.61	gold quality
tibial artery	UBERON:0007610	97.61	gold quality
aorta	UBERON:0000947	97.59	gold quality
thoracic aorta	UBERON:0001515	97.58	gold quality
fundus of stomach	UBERON:0001160	97.53	gold quality
ascending aorta	UBERON:0001496	97.53	gold quality
upper lobe of left lung	UBERON:0008952	97.52	gold quality
gall bladder	UBERON:0002110	97.50	gold quality
upper lobe of lung	UBERON:0008948	97.48	gold quality
endocervix	UBERON:0000458	97.46	gold quality
rectum	UBERON:0001052	97.41	gold quality
tibial nerve	UBERON:0001323	97.37	gold quality
smooth muscle tissue	UBERON:0001135	97.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

144 targeting CTDSP2, 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-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 4)

• These results suggest that SCP2 is involved in promoter clearance during steroid-activated transcription. (PMID:16724108)
• SCP2 acts as a phosphatase for regulatory phosphorylations in the linker region of Smad1 and Smad2 (PMID:17085434)
• CTDSP2 induces p21(Cip1/Waf1) through increasing the activity of Ras. (PMID:25990325)
• Tumor suppressor properties of the small C-terminal domain phosphatases in non-small cell lung cancer. (PMID:31774910)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctdsp2	ENSDARG00000036102
mus_musculus	Ctdsp2	ENSMUSG00000078429
rattus_norvegicus	Ctdsp2	ENSRNOG00000068220
drosophila_melanogaster	hzg	FBGN0036556
caenorhabditis_elegans	scpl-1	WBGENE00007054

Paralogs (5): TIMM50 (ENSG00000105197), CTDSPL2 (ENSG00000137770), CTDSP1 (ENSG00000144579), CTDSPL (ENSG00000144677), CTDNEP1 (ENSG00000175826)

Protein

Protein identifiers

Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 — O14595 (reviewed: O14595)

Alternative names: Nuclear LIM interactor-interacting factor 2, Protein OS-4, Small C-terminal domain phosphatase 2, Small CTD phosphatase 2

All UniProt accessions (6): F8VYL0, O14595, F8W184, F8W1I1, H0YI12, H0YI29

UniProt curated annotations — full annotation on UniProt →

Function. 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. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. May contribute to the development of sarcomas.

Subunit / interactions. Monomer. Interacts with REST.

Subcellular location. Nucleus.

Tissue specificity. Expression is restricted to non-neuronal tissues. Highest expression in pancreas and lowest in liver.

Cofactor. Binds 1 Mg(2+) ion per monomer.

Induction. In primary sarcomas.

RefSeq proteins (1): NP_005721* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004274	FCP1_dom	Domain
IPR011948	Dullard_phosphatase	Domain
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR040078	RNA_Pol_CTD_Phosphatase	Family
IPR050365	TIM50	Family

Pfam: PF03031

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (33 total): strand 11, helix 9, binding site 3, turn 2, active site 2, site 2, chain 1, domain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Q5E	X-RAY DIFFRACTION	2.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14595-F1	78.73	0.66

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 (4): 107 (4-aspartylphosphate intermediate); 109 (proton donor); 163 (transition state stabilizer); 201 (transition state stabilizer)

Ligand- & substrate-binding residues (3): 107; 109; 218

Post-translational modifications (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes

MSigDB gene sets: 689 (showing top): GOBP_LIPID_MODIFICATION, MODULE_52, GOBP_FATTY_ACID_CATABOLIC_PROCESS, AAGCAAT_MIR137, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, PEREZ_TP63_TARGETS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH

GO Biological Process (4): protein dephosphorylation (GO:0006470), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), regulation of transcription by RNA polymerase II (GO:0006357), protein transport (GO:0015031)

GO Molecular Function (7): RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (6): nucleoplasm (GO:0005654), nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM23 mitochondrial import inner membrane translocase complex (GO:0005744), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
IRE1alpha activates chaperones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
dephosphorylation	1
protein modification process	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein serine/threonine phosphatase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
nuclear lumen	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1

Protein interactions and networks

STRING

1297 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTDSP2	MATN3	O15232	925
CTDSP2	FRZB	Q92765	886
CTDSP2	ASPN	Q9BXN1	840
CTDSP2	GDF5	P43026	749
CTDSP2	CTDP1	Q9Y5B0	744
CTDSP2	REST	Q13127	736
CTDSP2	GTF2F1	P35269	518
CTDSP2	PTH2R	P49190	496
CTDSP2	OS9	Q13438	471
CTDSP2	RBM46	Q8TBY0	440
CTDSP2	ACTL6B	O94805	434
CTDSP2	DYM	Q7RTS9	427
CTDSP2	KCNN4	O15554	427
CTDSP2	STMN2	Q93045	425
CTDSP2	PHF10	Q8WUB8	424
CTDSP2	DPF1	Q92782	424

IntAct

48 interactions, top by confidence:

A	B	Type	Score
CTDSP2	CDCA3	psi-mi:“MI:0915”(physical association)	0.900
CDCA3	CTDSP2	psi-mi:“MI:0915”(physical association)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AR	CTDSP2	psi-mi:“MI:0915”(physical association)	0.580
CTDSP2	AR	psi-mi:“MI:0915”(physical association)	0.580
CTDSP2	N4BP3	psi-mi:“MI:0915”(physical association)	0.560
CTDSP2	LCN2	psi-mi:“MI:0915”(physical association)	0.560
tax	CTDSP2	psi-mi:“MI:0915”(physical association)	0.560
CTDSP2	tax	psi-mi:“MI:0915”(physical association)	0.560
CTDSP1	CTDSP2	psi-mi:“MI:0914”(association)	0.530
CTDSP2	ZMYM6	psi-mi:“MI:0914”(association)	0.530
SMAD1	CTDSP2	psi-mi:“MI:0915”(physical association)	0.400
GPA33	CTDSP2	psi-mi:“MI:0915”(physical association)	0.400
CTDSP2	CSF1R	psi-mi:“MI:0915”(physical association)	0.370
CTDSP2	TYRO3	psi-mi:“MI:0915”(physical association)	0.370
CTDSP2	INSRR	psi-mi:“MI:0915”(physical association)	0.370
CTDSP2	PTK7	psi-mi:“MI:0915”(physical association)	0.370
CTDSP2	EPHA3	psi-mi:“MI:0915”(physical association)	0.370
CTDSP2	EPHA1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (108): CDCA3 (Two-hybrid), CTDSP2 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), POM121 (Affinity Capture-MS), ZC3H3 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), MAP7D1 (Affinity Capture-MS), INTS6 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), CDCA3 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), SETD1A (Affinity Capture-MS), UBTF (Affinity Capture-MS), NEK4 (Affinity Capture-MS)

ESM2 similar proteins: A4QNX6, M9PFN0, O14595, O15194, O19111, O59697, O80673, P09217, P32019, P53681, P58465, P58466, Q00IB6, Q02956, Q05513, Q05D32, Q08BB5, Q09315, Q09695, Q14BI7, Q1EHT7, Q30DN6, Q3KQB6, Q3MHU3, Q5F3Z7, Q5XIK8, Q5XUN4, Q5ZI74, Q62240, Q66KM5, Q75WV3, Q801R4, Q8BG15, Q8BX07, Q8K337, Q8K4T5, Q8L7M4, Q8NDG6, Q8SV03, Q9BY66

Diamond homologs: A4QNX6, M9PFN0, O13636, O14595, O15194, O59718, O95476, P0CN66, P0CN67, P38757, P58465, P58466, Q02776, Q05D32, Q07800, Q07949, Q08BB5, Q09695, Q1RMV9, Q20432, Q28HW9, Q29I63, Q3B7T6, Q3KQB6, Q3TP92, Q3ZCQ8, Q4I099, Q4PEW9, Q4WI16, Q54GB2, Q59W44, Q5B4P0, Q5F3Z7, Q5RAJ8, Q5S7T7, Q5U395, Q5U3T3, Q5XIK8, Q61C05, Q66KM5

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CTDSP2	down-regulates	SMAD1	dephosphorylation
CTDSP2	“up-regulates activity”	SMAD3	dephosphorylation
CTDSP2	“down-regulates activity”	SMAD2	dephosphorylation
CTDSP2	“down-regulates activity”	SMAD1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	9
Uncertain significance	216
Likely benign	235
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

1259 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57823482:T:TA	donor_gain	1.0000
12:57823483:C:A	donor_gain	1.0000
12:57823726:ACCT:A	acceptor_loss	1.0000
12:57823728:CTGGT:C	acceptor_loss	1.0000
12:57823812:T:TA	donor_gain	1.0000
12:57823902:A:AC	donor_gain	1.0000
12:57823902:ACTG:A	donor_gain	1.0000
12:57823903:C:CC	donor_gain	1.0000
12:57823903:CTG:C	donor_gain	1.0000
12:57823903:CTGC:C	donor_gain	1.0000
12:57824085:GCATA:G	acceptor_gain	1.0000
12:57824086:CATA:C	acceptor_gain	1.0000
12:57824086:CATAC:C	acceptor_gain	1.0000
12:57824087:ATA:A	acceptor_gain	1.0000
12:57824088:TA:T	acceptor_gain	1.0000
12:57824088:TACTA:T	acceptor_loss	1.0000
12:57824089:ACTAG:A	acceptor_loss	1.0000
12:57824090:C:CC	acceptor_gain	1.0000
12:57824091:T:C	acceptor_loss	1.0000
12:57824223:GTA:G	donor_loss	1.0000
12:57824224:TAC:T	donor_loss	1.0000
12:57824225:ACCTT:A	donor_loss	1.0000
12:57824226:CCTTG:C	donor_loss	1.0000
12:57824317:CAC:C	acceptor_gain	1.0000
12:57824321:T:A	acceptor_loss	1.0000
12:57826340:GCTCA:G	donor_loss	1.0000
12:57826341:CTCAC:C	donor_loss	1.0000
12:57826342:TCACC:T	donor_loss	1.0000
12:57826343:CA:C	donor_loss	1.0000
12:57826344:A:AG	donor_loss	1.0000

AlphaMissense

1775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57823684:A:G	L245S	1.000
12:57823712:A:G	W236R	1.000
12:57823712:A:T	W236R	1.000
12:57823940:G:C	N218K	1.000
12:57823940:G:T	N218K	1.000
12:57823944:T:A	D217V	1.000
12:57823944:T:G	D217A	1.000
12:57823991:C:A	K201N	1.000
12:57823991:C:G	K201N	1.000
12:57823995:A:T	V200D	1.000
12:57824089:A:G	Y169H	1.000
12:57824236:G:C	S165R	1.000
12:57824236:G:T	S165R	1.000
12:57824238:T:G	S165R	1.000
12:57824243:G:A	T163I	1.000
12:57824245:G:C	F162L	1.000
12:57824245:G:T	F162L	1.000
12:57824247:A:G	F162L	1.000
12:57824302:C:A	R143S	1.000
12:57824302:C:G	R143S	1.000
12:57824303:C:A	R143M	1.000
12:57824303:C:G	R143T	1.000
12:57827015:A:T	L112H	1.000
12:57827021:T:A	E110V	1.000
12:57827024:T:A	D109V	1.000
12:57827027:A:G	L108P	1.000
12:57827030:T:A	D107V	1.000
12:57823675:A:G	L248P	0.999
12:57823684:A:C	L245W	0.999
12:57823693:T:A	D242V	0.999

dbSNP variants (sampled 300 via entrez): RS1000144335 (12:57837080 G>A), RS1000210181 (12:57827083 G>A), RS1000324911 (12:57830658 T>G), RS1000466102 (12:57845806 C>A), RS1000484107 (12:57846523 C>A,T), RS1000580732 (12:57831952 G>A,C,T), RS1000709137 (12:57825205 G>A), RS1000739833 (12:57825596 G>T), RS1000807797 (12:57839894 T>C), RS1000873795 (12:57839060 T>C,G), RS1000892133 (12:57833799 C>T), RS1000944985 (12:57847290 A>G), RS1000951240 (12:57847210 G>A), RS1001032806 (12:57819486 G>A), RS1001347947 (12:57831451 CAA>C,CA,CAAA)

Disease associations

OMIM: gene MIM:608711 | 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

5 associations (top):

Study	Trait	p-value
GCST008279_4	Trochanter size	3.000000e-09
GCST008839_491	Height	1.000000e-10
GCST009391_775	Metabolite levels	6.000000e-06
GCST010002_217	Refractive error	6.000000e-174
GCST90002383_8	Hematocrit	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010393	sphingomyelin 18:0 measurement
EFO:0004348	hematocrit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	3
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Estradiol	affects expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases methylation, decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
beta-methylcholine	affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
mono(carboxy-isooctyl)phthalate	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Air Pollutants	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SK02	HAP1 CTDSP2 (-) 1	Cancer cell line	Male
CVCL_SK03	HAP1 CTDSP2 (-) 2	Cancer cell line	Male

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