NOP10

Summary

NOP10 (NOP10 ribonucleoprotein, HGNC:14378) is a protein-coding gene on chromosome 15q14, encoding H/ACA ribonucleoprotein complex subunit 3 (Q9NPE3). Required for ribosome biogenesis and telomere maintenance. It is a common-essential gene (DepMap: required in 95.1% of cancer cell lines).

This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA2 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nop10p.

Source: NCBI Gene 55505 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyskeratosis congenita, autosomal recessive 1 (Strong, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 90 total — 1 pathogenic
• Phenotypes (HPO): 94
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 95.1% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_018648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14378
Approved symbol	NOP10
Name	NOP10 ribonucleoprotein
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	NOP10P, MGC70651
Ensembl gene	ENSG00000182117
Ensembl biotype	protein_coding
OMIM	606471
Entrez	55505

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000328848, ENST00000557912, ENST00000699926, ENST00000699934, ENST00000699935, ENST00000699936, ENST00000699937, ENST00000699938, ENST00000699939

RefSeq mRNA: 1 — MANE Select: NM_018648 NM_018648

CCDS: CCDS10037

Canonical transcript exons

ENST00000328848 — 2 exons

Exon	Start	End
ENSE00003978031	34341719	34342108
ENSE00003978034	34343020	34343136

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 179.6805 / max 979.6018, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149250	174.1903	1827
149249	5.4902	1681

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.88	gold quality
rectum	UBERON:0001052	98.87	gold quality
leukocyte	CL:0000738	98.86	gold quality
mononuclear cell	CL:0000842	98.85	gold quality
granulocyte	CL:0000094	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	98.79	gold quality
islet of Langerhans	UBERON:0000006	98.76	gold quality
smooth muscle tissue	UBERON:0001135	98.63	gold quality
apex of heart	UBERON:0002098	98.60	gold quality
right adrenal gland	UBERON:0001233	98.55	gold quality
spleen	UBERON:0002106	98.48	gold quality
oocyte	CL:0000023	98.47	gold quality
left adrenal gland	UBERON:0001234	98.47	gold quality
right adrenal gland cortex	UBERON:0035827	98.47	gold quality
stromal cell of endometrium	CL:0002255	98.42	gold quality
left adrenal gland cortex	UBERON:0035825	98.41	gold quality
thoracic aorta	UBERON:0001515	98.39	gold quality
peritoneum	UBERON:0002358	98.39	gold quality
omental fat pad	UBERON:0010414	98.39	gold quality
ascending aorta	UBERON:0001496	98.38	gold quality
heart right ventricle	UBERON:0002080	98.38	gold quality
upper lobe of left lung	UBERON:0008952	98.33	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.32	gold quality
descending thoracic aorta	UBERON:0002345	98.31	gold quality
upper lobe of lung	UBERON:0008948	98.27	gold quality
left coronary artery	UBERON:0001626	98.26	gold quality
adrenal cortex	UBERON:0001235	98.24	gold quality
heart left ventricle	UBERON:0002084	98.22	gold quality
cardiac ventricle	UBERON:0002082	98.19	gold quality
coronary artery	UBERON:0001621	98.14	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	83.52
E-MTAB-6701	yes	48.41
E-CURD-88	yes	12.51
E-MTAB-5061	yes	6.35
E-ENAD-17	no	961.61
E-CURD-10	no	563.91
E-GEOD-109979	no	345.39
E-HCAD-8	no	43.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting NOP10, 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-4715-3P	99.98	66.03	670
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 95.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• NOP10 has a role in the telomerase complex and telomere maintenance, and in autosomal recessive dyskeratosis congenita (PMID:17507419)
• Effects of dyskeratosis congenita mutations in NOP10 on assembly of H/ACA pre-RNPs (PMID:20008900)
• Indian aplastic anemia patients did not have NOP10 mutations. (PMID:25906515)
• Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis. (PMID:32554502)
• Acute depletion of telomerase components DKC1 and NOP10 induces oxidative stress and disrupts ribosomal biogenesis via NPM1 and activation of the P53 pathway. (PMID:32910990)
• Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer. (PMID:33161513)
• NOP10 predicts lung cancer prognosis and its associated small nucleolar RNAs drive proliferation and migration. (PMID:33288886)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nop10	ENSDARG00000104227
mus_musculus	Nop10	ENSMUSG00000027133
rattus_norvegicus	Nop10	ENSRNOG00000005184
rattus_norvegicus	Nop10l1	ENSRNOG00000055484
rattus_norvegicus		ENSRNOG00000081470
drosophila_melanogaster	Nop10	FBGN0033548
caenorhabditis_elegans	nola-3	WBGENE00007708

Protein

Protein identifiers

H/ACA ribonucleoprotein complex subunit 3 — Q9NPE3 (reviewed: Q9NPE3)

Alternative names: Nucleolar protein 10, Nucleolar protein family A member 3, snoRNP protein NOP10

All UniProt accessions (8): Q9NPE3, A0A8V8TP28, A0A8V8TPD4, A0A8V8TPK8, A0A8V8TQE5, A0A8V8TQE9, A0A8V8TQT0, H0YM60

UniProt curated annotations — full annotation on UniProt →

Function. Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine (‘psi’) residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme.

Subunit / interactions. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3’-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1.

Subcellular location. Nucleus. Nucleolus. Cajal body.

Disease relevance. Dyskeratosis congenita, autosomal recessive, 1 (DKCB1) [MIM:224230] A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. The disease is caused by variants affecting the gene represented in this entry. Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 2 (CHINE2) [MIM:620425] An autosomal recessive disorder characterized by infantile onset of steroid-resistant nephrotic syndrome, cataracts, sensorineural deafness, and enterocolitis. It results in death in early childhood. The disease may be caused by variants affecting the gene represented in this entry. Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 9 (PFBMFT9) [MIM:620400] An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other features include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk. Phenotype, age at onset, and severity are determined by telomere length. PFBMFT9 is characterized by the development of pulmonary fibrosis or hematologic abnormalities in adulthood. Liver disease may also be present. There is incomplete penetrance and evidence of genetic anticipation. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NOP10 family.

RefSeq proteins (1): NP_061118* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007264	H/ACA_rnp_Nop10	Family
IPR036756	H/ACA_rnp_Nop10_sf	Homologous_superfamily

Pfam: PF04135

UniProt features (10 total): strand 4, sequence variant 3, helix 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8OUE	ELECTRON MICROSCOPY	2.7
9QB2	ELECTRON MICROSCOPY	3
8OUF	ELECTRON MICROSCOPY	3.1
7TRC	ELECTRON MICROSCOPY	3.3
7BGB	ELECTRON MICROSCOPY	3.4
9QB3	ELECTRON MICROSCOPY	3.9
7V9A	ELECTRON MICROSCOPY	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPE3-F1	94.60	0.89

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-6790901	rRNA modification in the nucleus and cytosol

MSigDB gene sets: 400 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, chr15q14, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_PSEUDOURIDINE_SYNTHESIS, CCANNAGRKGGC_UNKNOWN, GOBP_RNA_MODIFICATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOBP_DNA_BIOSYNTHETIC_PROCESS

GO Biological Process (7): pseudouridine synthesis (GO:0001522), telomere maintenance via telomerase (GO:0007004), rRNA pseudouridine synthesis (GO:0031118), snRNA pseudouridine synthesis (GO:0031120), telomerase RNA localization to Cajal body (GO:0090671), rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

GO Molecular Function (5): RNA binding (GO:0003723), box H/ACA snoRNA binding (GO:0034513), telomerase RNA binding (GO:0070034), protein binding (GO:0005515), snoRNA binding (GO:0030515)

GO Cellular Component (11): nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), sno(s)RNA-containing ribonucleoprotein complex (GO:0005732), nuclear body (GO:0016604), box H/ACA snoRNP complex (GO:0031429), box H/ACA scaRNP complex (GO:0072589), box H/ACA telomerase RNP complex (GO:0090661), nucleus (GO:0005634), nucleolus (GO:0005730), Cajal body (GO:0015030), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Extension of Telomeres	1
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	4
catalytic complex	3
box H/ACA RNP complex	3
pseudouridine synthesis	2
RNA binding	2
nuclear lumen	2
ribonucleoprotein complex	2
intracellular membraneless organelle	2
RNA modification	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
rRNA modification	1
snRNA modification	1
RNA localization to Cajal body	1
telomerase RNA localization	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
snoRNA binding	1
binding	1
cellular anatomical structure	1
nucleoplasm	1
nucleolus	1
Cajal body	1
telomerase holoenzyme complex	1
intracellular membrane-bounded organelle	1
nuclear ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

2278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOP10	NHP2	Q9NX24	999
NOP10	DKC1	O60832	999
NOP10	TERT	O14746	998
NOP10	WRAP53	Q9BUR4	998
NOP10	GAR1	Q9NY12	986
NOP10	SHQ1	Q6PI26	968
NOP10	RUVBL2	Q9Y230	959
NOP10	RUVBL1	P82276	936
NOP10	FBL	P22087	920
NOP10	TINF2	Q9BSI4	902
NOP10	CTC1	Q2NKJ3	855
NOP10	NOP58	Q9Y2X3	811
NOP10	NOP56	O00567	810
NOP10	SNU13	P55769	810
NOP10	RTEL1	Q9NZ71	746

IntAct

81 interactions, top by confidence:

A	B	Type	Score
NHP2	NOP10	psi-mi:“MI:0915”(physical association)	0.920
NOP10	NHP2	psi-mi:“MI:0915”(physical association)	0.920
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
GAR1	DKC1	psi-mi:“MI:0914”(association)	0.790
DKC1	TERT	psi-mi:“MI:0915”(physical association)	0.750
DKC1	SHQ1	psi-mi:“MI:0914”(association)	0.670
CABP2	NOP10	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	NOP10	psi-mi:“MI:0915”(physical association)	0.560
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
HMBOX1	DKC1	psi-mi:“MI:0914”(association)	0.500
Snu13		psi-mi:“MI:0915”(physical association)	0.400
Ppp4c	NAP1L1	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
NAF1	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (129): NHP2 (Two-hybrid), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NHP2 (Co-fractionation), NOP10 (Synthetic Lethality), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), NOP10 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K4Z9G8, A0A8D9PH56, A4QK62, A4QKX5, C6Y4B1, C7U330, G2TRS1, O06472, P0C5R1, P0CAJ0, P0CE99, P0CY14, P0CY15, P0DTH8, P12320, P13636, P16515, P34830, P51701, P54446, P68353, P68941, P68942, P69469, P84771, P84772, P86274, Q08259, Q09122, Q0TFN3, Q1J8A6, Q1JDC8, Q1JIF2, Q1JNA1, Q1R9L0, Q3E804, Q3V4T4, Q48V42, Q66013, Q6CSZ0

Diamond homologs: A3DM90, A4G0L3, A5UMA9, A6UQY9, A6UUW5, A6VHX2, A8AAJ4, A9A115, A9A8V7, B6YT36, B8D6L8, C3MPG2, C3MYF0, C3N544, C3NDP2, C3NI09, C4KGP7, C5A500, C6A1Z6, O27362, O29724, P81303, Q12W64, Q18KQ9, Q2NE61, Q46C79, Q5JE48, Q5UX23, Q6LWK3, Q6Q547, Q8TT00, Q8TY85, Q8U1R4, Q8ZTY6, Q973G1, Q97Z78, Q9CQS2, Q9HIX4, Q9NPE3, Q9V0E3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NOP10	“up-regulates activity”	TERT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Telomere Extension By Telomerase	5	48.6×	1e-05
rRNA modification in the nucleus and cytosol	6	23.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance via telomerase	5	55.5×	1e-05
RNA processing	5	16.6×	1e-03
rRNA processing	7	15.0×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	43
Likely benign	21
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2506513	NM_018648.4(NOP10):c.47C>T (p.Thr16Met)	Pathogenic

SpliceAI

246 predictions. Top by Δscore:

Variant	Effect	Δscore
15:34342115:C:CT	acceptor_gain	1.0000
15:34342116:A:T	acceptor_gain	1.0000
15:34343014:CCTCA:C	donor_loss	1.0000
15:34343015:CTCAC:C	donor_loss	1.0000
15:34343018:ACC:A	donor_loss	1.0000
15:34342135:CAG:C	acceptor_gain	0.9900
15:34342185:A:C	acceptor_gain	0.9900
15:34343018:A:AC	donor_gain	0.9900
15:34343019:C:CC	donor_gain	0.9900
15:34343019:CCTT:C	donor_gain	0.9900
15:34343042:C:CA	donor_gain	0.9900
15:34342104:AATTT:A	acceptor_gain	0.9800
15:34342106:TTT:T	acceptor_gain	0.9800
15:34342108:TC:T	acceptor_loss	0.9800
15:34342109:C:CC	acceptor_gain	0.9800
15:34342115:C:T	acceptor_gain	0.9800
15:34342136:A:T	acceptor_gain	0.9800
15:34343082:ATAAG:A	donor_gain	0.9800
15:34342105:ATTT:A	acceptor_gain	0.9700
15:34342107:TT:T	acceptor_gain	0.9700
15:34342110:T:A	acceptor_loss	0.9700
15:34342121:C:CT	acceptor_gain	0.9600
15:34342166:A:T	acceptor_gain	0.9600
15:34342137:G:GC	acceptor_gain	0.9500
15:34342168:C:CT	acceptor_gain	0.9500
15:34342170:C:CT	acceptor_gain	0.9500
15:34342123:CAGAA:C	acceptor_gain	0.9400
15:34343013:T:A	donor_gain	0.9400
15:34342171:G:T	acceptor_gain	0.9300
15:34342184:CA:C	acceptor_gain	0.9300

AlphaMissense

410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:34342058:G:C	F35L	1.000
15:34342058:G:T	F35L	1.000
15:34342060:A:G	F35L	1.000
15:34342016:C:A	K49N	0.999
15:34342016:C:G	K49N	0.999
15:34342048:C:G	D39H	0.999
15:34342053:G:T	P37Q	0.999
15:34342059:A:G	F35S	0.999
15:34342065:G:T	A33D	0.999
15:34342070:A:C	H31Q	0.999
15:34342070:A:T	H31Q	0.999
15:34342072:G:C	H31D	0.999
15:34342074:G:T	A30D	0.999
15:34343031:A:G	Y15H	0.999
15:34342047:T:A	D39V	0.998
15:34342054:G:A	P37S	0.998
15:34342059:A:C	F35C	0.998
15:34342060:A:C	F35V	0.998
15:34342060:A:T	F35I	0.998
15:34342068:G:T	P32H	0.998
15:34342069:G:A	P32S	0.998
15:34342071:T:C	H31R	0.998
15:34342072:G:T	H31N	0.998
15:34342039:A:G	S42P	0.997
15:34342047:T:G	D39A	0.997
15:34343066:A:G	L3P	0.997
15:34343066:A:T	L3H	0.997
15:34342018:T:C	K49E	0.996
15:34342046:G:C	D39E	0.996
15:34342046:G:T	D39E	0.996

dbSNP variants (sampled 300 via entrez): RS1000210292 (15:34341302 ATAAGT>A), RS1000565122 (15:34341827 A>G), RS1001120306 (15:34341622 G>T), RS1002955445 (15:34344945 A>G,T), RS1003290814 (15:34343345 G>A,C,T), RS1003351670 (15:34344110 T>A,C), RS1003552438 (15:34343558 G>A,T), RS1004056011 (15:34341679 T>A,C), RS1004991424 (15:34342510 G>T), RS1005085585 (15:34342192 T>C,G), RS1005846427 (15:34344308 C>T), RS1006088010 (15:34344617 C>T), RS1006451873 (15:34344796 A>C,G), RS1007203791 (15:34344755 C>A,T), RS1007668324 (15:34344519 A>T)

Disease associations

OMIM: gene MIM:606471 | disease phenotypes: MIM:224230, MIM:620400, MIM:620425, MIM:127550

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal recessive 1	Strong	Autosomal recessive
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9	Moderate	Autosomal dominant
telomere syndrome	Moderate	Autosomal recessive
dyskeratosis congenita	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9	Limited	AD

Mondo (6): dyskeratosis congenita, autosomal recessive 1 (MONDO:0009136), pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9 (MONDO:0957294), cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 2 (MONDO:0958193), dyskeratosis congenita (MONDO:0015780), hereditary neoplastic syndrome (MONDO:0015356), telomere syndrome (MONDO:0100137)

Orphanet (2): Dyskeratosis congenita (Orphanet:1775), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000035	Abnormal testis morphology
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000579	Nasolacrimal duct obstruction
HP:0000600	Abnormality of the pharynx
HP:0000653	Sparse eyelashes
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000691	Microdontia
HP:0000704	Periodontitis
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0000972	Palmoplantar hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C565611	Dyskeratosis Congenita, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066393 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sodium arsenite	increases expression	1
chloropicrin	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Cisplatin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651923	Binding	Binding affinity to human NOP10 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT04638517	PHASE2	TERMINATED	The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT06477614	PHASE1	RECRUITING	Anti-cancer DC Cell Vaccination to Treat Solid Tumors
NCT06817590	PHASE1	RECRUITING	Nucleoside Therapy in Patients With Telomere Biology Disorders
NCT05813327	PHASE1	ACTIVE_NOT_RECRUITING	Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma
NCT00455312	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
NCT01001598	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00499070	Not specified	COMPLETED	Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02162420	Not specified	COMPLETED	Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT04959188	Not specified	COMPLETED	Needs Assessment for Individuals and Families Affected by Dyskeratosis Congenita (DC) and Related Telomere Biology Disorders (TBD)
NCT06731036	Not specified	AVAILABLE	Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
NCT06726642	Not specified	RECRUITING	CfDNA in Hereditary And High-risk Malignancies 2