NOPCHAP1

Summary

NOPCHAP1 (NOP protein chaperone 1, HGNC:28628) is a protein-coding gene on chromosome 12q23.3, encoding NOP protein chaperone 1 (Q8N5I9). Client-loading PAQosome/R2TP complex cofactor that selects NOP58 to promote box C/D small nucleolar ribonucleoprotein (snoRNP) assembly. It is a selective cancer dependency (DepMap: 69.3% of cell lines).

Enables box C/D methylation guide snoRNP complex binding activity. Involved in box C/D snoRNP assembly. Predicted to be located in nucleus.

Source: NCBI Gene 121053 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total
• Cancer dependency (DepMap): dependent in 69.3% of screened cell lines
• MANE Select transcript: NM_152318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28628
Approved symbol	NOPCHAP1
Name	NOP protein chaperone 1
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC40397, DDSR1
Ensembl gene	ENSG00000151131
Ensembl biotype	protein_coding
Entrez	121053

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000280749, ENST00000547750, ENST00000548583, ENST00000552951, ENST00000622317, ENST00000637147, ENST00000935673

RefSeq mRNA: 1 — MANE Select: NM_152318 NM_152318

CCDS: CCDS41825

Canonical transcript exons

ENST00000552951 — 4 exons

Exon	Start	End
ENSE00000997818	104988167	104988253
ENSE00000997819	104986316	104986467
ENSE00000997820	104991712	104991848
ENSE00002357586	104994478	105017625

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 89.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9910 / max 185.8348, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127786	23.9910	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.40	gold quality
body of pancreas	UBERON:0001150	88.43	gold quality
oocyte	CL:0000023	86.19	gold quality
corpus epididymis	UBERON:0004359	85.87	gold quality
calcaneal tendon	UBERON:0003701	85.67	gold quality
mucosa of transverse colon	UBERON:0004991	85.22	gold quality
cortical plate	UBERON:0005343	85.08	gold quality
pancreas	UBERON:0001264	84.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.01	gold quality
parotid gland	UBERON:0001831	84.00	gold quality
body of stomach	UBERON:0001161	83.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.77	gold quality
descending thoracic aorta	UBERON:0002345	82.51	gold quality
granulocyte	CL:0000094	82.33	gold quality
stomach	UBERON:0000945	82.21	gold quality
colonic epithelium	UBERON:0000397	82.01	gold quality
ganglionic eminence	UBERON:0004023	81.87	gold quality
right lobe of liver	UBERON:0001114	81.56	gold quality
omental fat pad	UBERON:0010414	81.54	gold quality
peritoneum	UBERON:0002358	81.52	gold quality
thoracic aorta	UBERON:0001515	81.50	gold quality
left coronary artery	UBERON:0001626	81.50	gold quality
ascending aorta	UBERON:0001496	81.46	gold quality
saliva-secreting gland	UBERON:0001044	81.36	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.18	gold quality
pancreatic ductal cell	CL:0002079	81.10	silver quality
lower esophagus mucosa	UBERON:0035834	81.06	gold quality
tendon	UBERON:0000043	81.03	gold quality
minor salivary gland	UBERON:0001830	80.93	gold quality
caput epididymis	UBERON:0004358	80.91	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	6782.90
E-GEOD-75688	yes	3684.71
E-GEOD-130473	yes	3275.12
E-MTAB-6678	yes	2855.43
E-GEOD-75367	yes	2122.05
E-GEOD-106540	yes	2099.27
E-CURD-97	yes	1696.22
E-CURD-89	yes	646.51
E-GEOD-81547	yes	563.50
E-ANND-3	yes	16.94
E-MTAB-5061	yes	14.56
E-CURD-112	yes	14.40
E-HCAD-10	yes	9.27
E-MTAB-7249	no	875.78
E-MTAB-10137	no	281.28

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis. (PMID:33367824)
• Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation. (PMID:39014289)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nopchap1	ENSMUSG00000020255
rattus_norvegicus	Nopchap1	ENSRNOG00000008696

Protein

Protein identifiers

NOP protein chaperone 1 — Q8N5I9 (reviewed: Q8N5I9)

All UniProt accessions (4): Q8N5I9, A0A087WT30, A0A1B0GW16, J3KN91

UniProt curated annotations — full annotation on UniProt →

Function. Client-loading PAQosome/R2TP complex cofactor that selects NOP58 to promote box C/D small nucleolar ribonucleoprotein (snoRNP) assembly. Acts as a bridge between NOP58 and the R2TP complex via RUVBL1:RUVBL2.

Subunit / interactions. Interacts with NOP58, RUVBL1 and RUVBL2; the interactions are direct and NOPCHAP1 bridges the association of NOP58 with RUVBL1:RUVBL2 even in absence of snoRNAs. The interactions with RUVBL1 and RUVBL2 are disrupted upon ATP binding.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_689531* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027921	NOPCHAP1	Family

Pfam: PF15370

UniProt features (10 total): modified residue 3, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5I9-F1	70.77	0.14

Functional residue map

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

Post-translational modifications (3): 34, 66, 178

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, WANG_LMO4_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SARTIPY_NORMAL_AT_INSULIN_RESISTANCE_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, chr12q23, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, GOBP_SMALL_NUCLEOLAR_RIBONUCLEOPROTEIN_COMPLEX_ASSEMBLY, GOBP_BOX_C_D_SNORNP_ASSEMBLY

GO Biological Process (1): box C/D snoRNP assembly (GO:0000492)

GO Molecular Function (2): box C/D methylation guide snoRNP complex binding (GO:0062064), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small nucleolar ribonucleoprotein complex assembly	1
snoRNP binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

877 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOPCHAP1	NOP58	Q9Y2X3	671
NOPCHAP1	RUVBL1	P82276	630
NOPCHAP1	ZNHIT2	Q9UHR6	572
NOPCHAP1	ZNHIT3	Q15649	564
NOPCHAP1	PALMD	Q9NP74	541
NOPCHAP1	RPAP3	Q9H6T3	455
NOPCHAP1	ZNHIT6	Q9NWK9	448
NOPCHAP1	PIH1D1	Q9NWS0	425
NOPCHAP1	THEM4	Q5T1C6	425
NOPCHAP1	GNAZ	P19086	416
NOPCHAP1	NOP56	O00567	410
NOPCHAP1	SNU13	P55769	406
NOPCHAP1	RUVBL2	Q9Y230	403
NOPCHAP1	NUFIP1	Q9UHK0	399
NOPCHAP1	SHQ1	Q6PI26	379

IntAct

32 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
NOP58	NOPCHAP1	psi-mi:“MI:0915”(physical association)	0.560
CT55	BLTP3B	psi-mi:“MI:0914”(association)	0.530
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
BMX	NOPCHAP1	psi-mi:“MI:0915”(physical association)	0.370
NOPCHAP1	TBC1D23	psi-mi:“MI:0915”(physical association)	0.370
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
Ruvbl2	TTI2	psi-mi:“MI:0914”(association)	0.350
KPNA1	MTA3	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
DNAJB6	DNAJB2	psi-mi:“MI:0914”(association)	0.350
SARS1	R3HCC1L	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
NOP58	AGPS	psi-mi:“MI:0914”(association)	0.350
RUVBL2	ASDURF	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
KPNA2	SETD1A	psi-mi:“MI:0914”(association)	0.350
KPNA5	SPOP	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
SPAG1	NOPCHAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Proximity Label-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), C12orf45 (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), C12orf45 (Affinity Capture-MS)

ESM2 similar proteins: A3LYF7, A5HWA8, B5X601, C3KJF2, C5E000, C6Y4A5, G2TRM6, O00566, O13758, O13910, O13964, O43088, O74517, O74857, O94693, P0CV38, P30261, P38326, Q02554, Q04418, Q10148, Q10200, Q10369, Q12334, Q12343, Q12373, Q177A7, Q1MTN9, Q2PE14, Q2TBJ0, Q6BWZ7, Q6CJ60, Q6CKH1, Q6CQ59, Q6FLB8, Q6FML0, Q6FNK3, Q754T8, Q810V0, Q8N5I9

Diamond homologs: Q2TBJ0, Q8N5I9, Q9CX66

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
NS1 Mediated Effects on Host Pathways	5	71.4×	1e-06
ISG15 antiviral mechanism	5	37.6×	2e-05
Viral Infection Pathways	5	7.7×	4e-03
Infectious disease	5	6.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein import into nucleus	5	24.0×	1e-04
protein stabilization	5	11.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4396 predictions. Top by Δscore:

Variant	Effect	Δscore
12:104986465:G:GT	donor_gain	1.0000
12:104986514:G:GT	donor_gain	1.0000
12:104986580:G:T	donor_gain	1.0000
12:104988162:TTCA:T	acceptor_loss	1.0000
12:104988164:CA:C	acceptor_loss	1.0000
12:104988166:GGT:G	acceptor_gain	1.0000
12:104988166:GGTA:G	acceptor_gain	1.0000
12:104988166:GGTAT:G	acceptor_gain	1.0000
12:104988249:TCCCT:T	donor_gain	1.0000
12:104988250:CCCT:C	donor_gain	1.0000
12:104988251:CCT:C	donor_gain	1.0000
12:104988252:CT:C	donor_gain	1.0000
12:104988252:CTGTA:C	donor_loss	1.0000
12:104988253:TGTA:T	donor_loss	1.0000
12:104988254:G:GG	donor_gain	1.0000
12:104988254:GTAA:G	donor_loss	1.0000
12:104988255:T:A	donor_loss	1.0000
12:104991710:A:AG	acceptor_gain	1.0000
12:104991711:G:GC	acceptor_gain	1.0000
12:104991711:GT:G	acceptor_gain	1.0000
12:104991711:GTA:G	acceptor_gain	1.0000
12:104991711:GTATT:G	acceptor_gain	1.0000
12:104991832:G:GG	donor_gain	1.0000
12:104991847:TGG:T	donor_loss	1.0000
12:104991848:GGTA:G	donor_loss	1.0000
12:104991850:T:A	donor_loss	1.0000
12:104994467:A:AG	acceptor_gain	1.0000
12:104994473:TGCAG:T	acceptor_loss	1.0000
12:104994474:GCAGG:G	acceptor_loss	1.0000
12:104994475:CAGG:C	acceptor_loss	1.0000

AlphaMissense

1221 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:104991732:T:C	F75L	0.993
12:104991734:T:A	F75L	0.993
12:104991734:T:G	F75L	0.993
12:104991753:G:C	A82P	0.992
12:104988247:A:C	S66R	0.990
12:104988249:T:A	S66R	0.990
12:104988249:T:G	S66R	0.990
12:104991747:G:C	A80P	0.987
12:104991733:T:C	F75S	0.983
12:104991766:T:C	L86P	0.981
12:104991801:T:C	F98L	0.972
12:104991803:C:A	F98L	0.972
12:104991803:C:G	F98L	0.972
12:104991733:T:G	F75C	0.970
12:104991736:T:A	L76H	0.969
12:104991745:T:C	M79T	0.969
12:104991736:T:C	L76P	0.968
12:104991847:T:G	M113R	0.963
12:104991848:G:A	M113I	0.963
12:104991848:G:C	M113I	0.963
12:104991848:G:T	M113I	0.963
12:104991745:T:G	M79R	0.961
12:104991841:T:A	I111K	0.960
12:104991757:A:T	N83I	0.956
12:104991736:T:G	L76R	0.952
12:104991802:T:C	F98S	0.951
12:104991745:T:A	M79K	0.948
12:104991766:T:A	L86Q	0.948
12:104991847:T:A	M113K	0.948
12:104991715:T:C	L69S	0.947

dbSNP variants (sampled 300 via entrez): RS1000137193 (12:104984950 A>G), RS1000213659 (12:105000396 C>G,T), RS1000268560 (12:104989869 A>G), RS1000268967 (12:105007616 C>T), RS1000304082 (12:104988471 G>A), RS1000358780 (12:104994405 T>C), RS1000429498 (12:104996032 T>G), RS1000482917 (12:105009096 T>G), RS1000536691 (12:104998930 G>T), RS1000565607 (12:104999994 C>T), RS1000651288 (12:105005877 A>T), RS1000861086 (12:105007965 A>G), RS1000983197 (12:105017179 C>T), RS1001008212 (12:105005555 T>C), RS1001087082 (12:105007651 C>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010923_1	Beta blocker survival benefit in heart failure with reduced ejection fraction (time to all cause mortality x beta blocker interaction)	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0007766	response to beta blocker

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases expression	4
Benzo(a)pyrene	increases expression	3
Cisplatin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
arsenite	increases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Potassium Dichromate	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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