NOP56

Summary

NOP56 (NOP56 ribonucleoprotein, HGNC:15911) is a protein-coding gene on chromosome 20p13, encoding Nucleolar protein 56 (O00567). Involved in the early to middle stages of 60S ribosomal subunit biogenesis. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

Nop56p is a yeast nucleolar protein that is part of a complex with the nucleolar proteins Nop58p and fibrillarin. Nop56p is required for assembly of the 60S ribosomal subunit and is involved in pre-rRNA processing. The protein encoded by this gene is similar in sequence to Nop56p and is also found in the nucleolus. Expansion of a GGCCTG repeat from 3-8 copies to 1500-2500 copies in an intron of this gene results in spinocerebellar ataxia 36. Multiple transcript variants encoding several different isoforms have been found for this gene, but the full-length nature of most of them has not been determined.

Source: NCBI Gene 10528 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 36 (Definitive, GenCC)
• Clinical variants (ClinVar): 123 total — 1 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15911
Approved symbol	NOP56
Name	NOP56 ribonucleoprotein
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	SCA36
Ensembl gene	ENSG00000101361
Ensembl biotype	protein_coding
OMIM	614154
Entrez	10528

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 14 protein_coding_CDS_not_defined, 10 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000329276, ENST00000415272, ENST00000445139, ENST00000460258, ENST00000462630, ENST00000466447, ENST00000467196, ENST00000467857, ENST00000469588, ENST00000470143, ENST00000471023, ENST00000480447, ENST00000480992, ENST00000484998, ENST00000490753, ENST00000492135, ENST00000494697, ENST00000496775, ENST00000612233, ENST00000616692, ENST00000651302, ENST00000860469, ENST00000932640, ENST00000932641, ENST00000932642, ENST00000932643, ENST00000932644, ENST00000945682

RefSeq mRNA: 1 — MANE Select: NM_006392 NM_006392

CCDS: CCDS13030

Canonical transcript exons

ENST00000329276 — 12 exons

Exon	Start	End
ENSE00000656429	2655934	2656034
ENSE00001951742	2652632	2652663
ENSE00003476153	2657929	2658393
ENSE00003492126	2654414	2654575
ENSE00003504861	2655595	2655746
ENSE00003532667	2655325	2655512
ENSE00003566163	2653279	2653393
ENSE00003575082	2656401	2656549
ENSE00003580604	2654749	2654947
ENSE00003603680	2652842	2652931
ENSE00003668231	2656774	2656895
ENSE00003673775	2657081	2657218

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.2492 / max 1067.8013, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183172	59.0224	1821
183171	4.2268	1696
183174	0.7362	343

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	98.63	gold quality
granulocyte	CL:0000094	98.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.13	gold quality
cerebellar hemisphere	UBERON:0002245	97.98	gold quality
cerebellar cortex	UBERON:0002129	97.90	gold quality
body of pancreas	UBERON:0001150	97.66	gold quality
right uterine tube	UBERON:0001302	97.66	gold quality
right ovary	UBERON:0002118	97.62	gold quality
left uterine tube	UBERON:0001303	97.60	gold quality
left ovary	UBERON:0002119	97.53	gold quality
lymph node	UBERON:0000029	97.51	gold quality
adenohypophysis	UBERON:0002196	97.40	gold quality
ventricular zone	UBERON:0003053	97.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.37	gold quality
mucosa of transverse colon	UBERON:0004991	97.31	gold quality
pituitary gland	UBERON:0000007	97.28	gold quality
spleen	UBERON:0002106	97.26	gold quality
lower esophagus mucosa	UBERON:0035834	97.24	gold quality
body of uterus	UBERON:0009853	97.20	gold quality
right frontal lobe	UBERON:0002810	97.18	gold quality
cerebellum	UBERON:0002037	97.17	gold quality
esophagus mucosa	UBERON:0002469	97.15	gold quality
ganglionic eminence	UBERON:0004023	97.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.06	gold quality
rectum	UBERON:0001052	96.97	gold quality
ovary	UBERON:0000992	96.93	gold quality
peritoneum	UBERON:0002358	96.87	gold quality
omental fat pad	UBERON:0010414	96.87	gold quality
skin of abdomen	UBERON:0001416	96.78	gold quality
right lobe of thyroid gland	UBERON:0001119	96.76	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-53	no	2391.69
E-MTAB-4850	no	978.66
E-MTAB-6524	no	335.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• hNop56p functions in the early to middle stages of 60 S subunit synthesis in human cells and has functional similarities with treacle-associated ribonucleoproteins (PMID:12777385)
• Data demonstrate that fibrillarin and Nop56 directly interact in vivo, and that this interaction is indispensable for the association of both proteins with the box C/D snoRNPs. (PMID:19331828)
• snoRNP assembly factor NUFIP can regulate the interactions between TIP48 and TIP49 and the core box C/D proteins. (PMID:19620283)
• Expansion of the intronic GGCCTG hexanucleotide repeat in NOP56 causes a unique form of spinocerebellar ataxias, SCA36, which shows not only ataxia but also motor neuron dysfunction. (PMID:21683323)
• We newly found intronic hexanucleotide GGCCTG gene expansion in NOP56 gene as the causative mutation in nine unrelated Japanese familial hereditary spinocerebellar ataxia patients (PMID:22353375)
• This study demonistrated that NOP56 mutation is response spinocerebellar ataxia 36 in Spainish family. (PMID:22492559)
• Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China, with its causative mutation as a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene, has been described. (PMID:26661328)
• Studies indicate that the causative mutation for spinocerebellar ataxias SCA36, namely intronic hexanucleotide GGCCTG expansion in NOP56 gene, has been identified. (PMID:26663071)
• Excess snoRNP core proteins prevent further production of NOP56 and instead trigger the generation of a cytoplasmic snoRD86-containing NOP56-derived lncRNA via the nonsense-mediated decay pathway. (PMID:30220559)
• This is the first report on the clinical aspect of ribosome biogenesis in pediatric BCP-ALL [B-cell precursor acute lymphoblastic leukemia ], and it shows that overexpression of CMYC and C/D box nucleoproteins FBL and NOP56 is an antecedent event in patients who subsequently relapse (PMID:32011831)
• Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo. (PMID:32375043)
• [Effect of piRNA NU13 in regulating biological behaviors of human Wilms tumor cells in vitro]. (PMID:33624590)
• A PRC2-independent function for EZH2 in regulating rRNA 2’-O methylation and IRES-dependent translation. (PMID:33795875)
• The roles of NOP56 in cancer and SCA36. (PMID:36741964)
• Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy. (PMID:38667292)
• Hexanucleotide repeat expansion in SCA36 reduces the expression of genes involved in ribosome biosynthesis and protein translation. (PMID:38811808)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nop56	ENSDARG00000012820
mus_musculus	Nop56	ENSMUSG00000027405
rattus_norvegicus	Nop56	ENSRNOG00000007128
caenorhabditis_elegans		WBGENE00010627

Paralogs (1): NOP58 (ENSG00000055044)

Protein

Protein identifiers

Nucleolar protein 56 — O00567 (reviewed: O00567)

Alternative names: Nucleolar protein 5A

All UniProt accessions (5): O00567, A0A494C128, H0Y653, H0YDU4, Q5JXT2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs).

Subunit / interactions. Part of a large pre-ribosomal ribonucleoprotein (RNP) complex, that consists of at least 62 ribosomal proteins, 45 nonribosomal proteins and both pre-rRNA and mature rRNA species. Within this complex directly interacts with TCOF1 in an RNA-independent manner. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles; the core proteins SNU13, NOP56, NOP58 and FBL or FBLL1 assemble stepwise onto the snoRNA. Interacts with NOP1 and NOP58. Interacts with NUFIP1, RUVBL1 and RUVBL2; RUVBL1:RUVBL2 seem to bridge the association of NOP56 with NUFIP1. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with NOP2 and FBL.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Nucleoplasm.

Disease relevance. Spinocerebellar ataxia 36 (SCA36) [MIM:614153] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA36 is characterized by complicated clinical features, with ataxia as the first symptom, followed by characteristic late-onset involvement of the motor neuron system. Ataxic symptoms, such as gait and truncal instability, ataxic dysarthria, and uncoordinated limbs, start in late forties to fifties. Characteristically, affected individuals exhibit tongue atrophy with fasciculation. Progression of motor neuron involvement is typically limited to the tongue and main proximal skeletal muscles in both upper and lower extremities. The disease is caused by variants affecting the gene represented in this entry. Caused by large hexanucleotide CGCCTG repeat expansions within intron 1. These expansions induce RNA foci and sequester the RNA-binding protein SRSF2. In addition, the transcription of MIR1292, a microRNA gene located just 19 bp 3’ of the GGCCTG repeat, is significantly decreased.

Similarity. Belongs to the NOP5/NOP56 family.

RefSeq proteins (1): NP_006383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002687	Nop_dom	Domain
IPR012974	NOP58/56_N	Domain
IPR012976	NOSIC	Domain
IPR036070	Nop_dom_sf	Homologous_superfamily
IPR042239	Nop_C	Homologous_superfamily
IPR045056	Nop56/Nop58	Family

Pfam: PF01798, PF08156

UniProt features (32 total): modified residue 15, cross-link 5, sequence variant 3, sequence conflict 3, compositionally biased region 3, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00567-F1	74.99	0.35

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 (20): 468, 511, 519, 520, 537, 561, 563, 569, 570, 579, 581, 87, 230, 240, 540, 564, 314, 359, 466, 467

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 307 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TSENG_IRS1_TARGETS_UP, GOBP_MATURATION_OF_SSU_RRNA, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GNF2_MCM5, GOBP_RNA_METHYLATION, GOBP_MRNA_MODIFICATION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET

GO Biological Process (3): rRNA processing (GO:0006364), ribosomal small subunit biogenesis (GO:0042274), ribosome biogenesis (GO:0042254)

GO Molecular Function (5): RNA binding (GO:0003723), snoRNA binding (GO:0030515), cadherin binding (GO:0045296), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515)

GO Cellular Component (11): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), sno(s)RNA-containing ribonucleoprotein complex (GO:0005732), cytoplasm (GO:0005737), membrane (GO:0016020), box C/D methylation guide snoRNP complex (GO:0031428), small-subunit processome (GO:0032040), pre-snoRNP complex (GO:0070761), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ribosome biogenesis	2
ribonucleoprotein complex biogenesis	2
nucleolus	2
nuclear lumen	2
ribonucleoprotein complex	2
RNA processing	1
rRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
cell adhesion molecule binding	1
enzyme binding	1
binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
box C/D RNP complex	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

3951 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOP56	FBL	P22087	999
NOP56	SNU13	P55769	998
NOP56	NOP58	Q9Y2X3	989
NOP56	RRP9	O43818	965
NOP56	TCOF1	Q13428	919
NOP56	NHP2	Q9NX24	879
NOP56	DKC1	O60832	865
NOP56	PIH1D1	Q9NWS0	835
NOP56	NOP10	Q9NPE3	810
NOP56	BMS1	Q14692	803
NOP56	NOLC1	Q14978	797
NOP56	RUVBL2	Q9Y230	759
NOP56	RUVBL1	P82276	752
NOP56	NOP14	P78316	752
NOP56	UTP4	Q969X6	742

IntAct

168 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RPL7A	NOP56	psi-mi:“MI:0914”(association)	0.640
NOP56	RPL7A	psi-mi:“MI:0914”(association)	0.640
NOP58	NOP56	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
RRP9	NOP56	psi-mi:“MI:0915”(physical association)	0.560
NOP56	SDCBP2	psi-mi:“MI:0915”(physical association)	0.560
BCOR	CBX4	psi-mi:“MI:0914”(association)	0.530
PCGF1	CBX4	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
NOP56	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TPTE	NOP56	psi-mi:“MI:2364”(proximity)	0.420
NOP56	HMOX2	psi-mi:“MI:0915”(physical association)	0.400
SNU13	NOP56	psi-mi:“MI:0915”(physical association)	0.400
Ybx1	MRPS18B	psi-mi:“MI:0915”(physical association)	0.400
Snu13		psi-mi:“MI:0915”(physical association)	0.400

BioGRID (849): NOP56 (Affinity Capture-RNA), NOP56 (Affinity Capture-RNA), NOP56 (Affinity Capture-RNA), NOP56 (Affinity Capture-RNA), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), NOP56 (Biochemical Activity), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), ABCF2 (Co-fractionation), ATAD3B (Co-fractionation)

ESM2 similar proteins: A1CL70, A1D688, A2QE38, A3LUT0, A5DHW0, A5E4V9, A6QYH8, A6RMY5, A6ZPE5, A7F2R6, A7TIF5, O00567, O04658, O94514, P0CP02, P0CP03, P0CP26, P0CP27, P0CP58, P0CP59, P39730, Q0CQH1, Q10251, Q12460, Q12499, Q1E1Q5, Q21276, Q2UC04, Q3SZ63, Q4PBF2, Q4R779, Q4WYK9, Q54MT2, Q55FI4, Q59S06, Q5B8G3, Q5RA29, Q6BIX6, Q6CG46, Q6CKR8

Diamond homologs: A1CL70, A1D688, A2QE38, A3LUT0, A5DHW0, A5E4V9, A6QYH8, A6RMY5, A6ZPE5, A7F2R6, A7TIF5, O00567, O04656, O04658, O94514, P0CP26, P0CP27, Q0CQH1, Q12460, Q12499, Q1E1Q5, Q21276, Q2UC04, Q3SZ63, Q4PBF2, Q4R779, Q4WYK9, Q54MT2, Q55FI4, Q58105, Q59S06, Q5B8G3, Q5RA29, Q6BIX6, Q6CG46, Q6CKR8, Q6DFW4, Q6FQ21, Q753I4, Q8X066

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NOP56	“form complex”	“U3 snoRNP”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Nonsense-Mediated Decay (NMD)	5	10.7×	3e-03
rRNA modification in the nucleus and cytosol	6	10.3×	1e-03
SARS-CoV-2 modulates host translation machinery	5	10.3×	3e-03
Influenza Viral RNA Transcription and Replication	5	9.9×	4e-03
Formation of the ternary complex, and subsequently, the 43S complex	5	9.9×	4e-03
Influenza Infection	6	9.7×	1e-03
rRNA processing in the nucleus and cytosol	6	8.8×	2e-03
Translation initiation complex formation	5	8.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	9	14.0×	2e-05
cytoplasmic translation	8	10.2×	3e-04
rRNA processing	8	7.8×	2e-03
translation	10	7.0×	4e-04
RNA splicing	10	6.0×	1e-03
regulation of cell cycle	10	5.1×	3e-03
DNA damage response	11	4.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	80
Likely benign	14
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1298312	NM_006392.4(NOP56):c.909G>A (p.Ala303=)	Likely pathogenic

SpliceAI

1765 predictions. Top by Δscore:

Variant	Effect	Δscore
20:2652899:G:GT	donor_gain	1.0000
20:2652932:G:GG	donor_gain	1.0000
20:2652933:T:G	donor_loss	1.0000
20:2653275:CCAG:C	acceptor_loss	1.0000
20:2653276:CAGG:C	acceptor_loss	1.0000
20:2653277:A:AG	acceptor_gain	1.0000
20:2653277:AGGT:A	acceptor_gain	1.0000
20:2653278:G:GG	acceptor_gain	1.0000
20:2653278:G:GT	acceptor_loss	1.0000
20:2653278:GGT:G	acceptor_gain	1.0000
20:2653278:GGTG:G	acceptor_gain	1.0000
20:2653390:GAAG:G	donor_gain	1.0000
20:2653391:AAG:A	donor_gain	1.0000
20:2653391:AAGG:A	donor_loss	1.0000
20:2653392:AG:A	donor_gain	1.0000
20:2653393:GG:G	donor_gain	1.0000
20:2653394:G:GG	donor_gain	1.0000
20:2653395:T:G	donor_loss	1.0000
20:2654410:T:TA	acceptor_gain	1.0000
20:2654746:TAG:T	acceptor_loss	1.0000
20:2654747:A:AG	acceptor_gain	1.0000
20:2654748:G:A	acceptor_loss	1.0000
20:2654748:G:GG	acceptor_gain	1.0000
20:2654748:GGA:G	acceptor_gain	1.0000
20:2654913:GA:G	donor_gain	1.0000
20:2654914:A:G	donor_gain	1.0000
20:2654919:G:GT	donor_gain	1.0000
20:2654945:CAGG:C	donor_loss	1.0000
20:2654946:AGG:A	donor_loss	1.0000
20:2654947:GGTAA:G	donor_loss	1.0000

AlphaMissense

3898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:2654871:G:C	D165H	1.000
20:2654872:A:T	D165V	1.000
20:2654889:T:C	S171P	1.000
20:2654899:T:C	L174P	1.000
20:2654911:T:C	L178P	1.000
20:2654925:A:G	N183D	1.000
20:2654927:T:A	N183K	1.000
20:2654927:T:G	N183K	1.000
20:2654938:T:C	M187T	1.000
20:2654939:G:A	M187I	1.000
20:2654939:G:C	M187I	1.000
20:2654939:G:T	M187I	1.000
20:2654940:C:A	R188S	1.000
20:2654941:G:C	R188P	1.000
20:2654944:T:A	V189D	1.000
20:2655328:G:C	E191D	1.000
20:2655328:G:T	E191D	1.000
20:2655329:T:A	W192R	1.000
20:2655329:T:C	W192R	1.000
20:2655341:C:G	H196D	1.000
20:2655344:T:C	F197L	1.000
20:2655345:T:C	F197S	1.000
20:2655346:T:A	F197L	1.000
20:2655346:T:G	F197L	1.000
20:2655354:T:C	L200P	1.000
20:2655494:G:C	A247P	1.000
20:2655507:C:T	S251F	1.000
20:2655512:G:C	G253R	1.000
20:2655512:G:T	G253C	1.000
20:2655595:G:A	G253D	1.000

dbSNP variants (sampled 300 via entrez): RS1000029440 (20:2652363 G>A,C), RS1000079108 (20:2657682 C>A,G,T), RS1000464675 (20:2652464 G>A,C), RS1000793400 (20:2657799 C>T), RS1001075836 (20:2652839 C>T), RS1002224395 (20:2658623 C>A,G,T), RS1002298295 (20:2653598 G>A), RS1002783952 (20:2653036 G>A,C,T), RS1002947284 (20:2650961 C>A), RS1003826440 (20:2656443 T>C), RS1004017372 (20:2653861 G>A), RS1004885087 (20:2654039 C>G,T), RS1005562615 (20:2652480 C>A,T), RS1006195725 (20:2652089 C>A,G,T), RS1006329746 (20:2650837 A>C,G)

Disease associations

OMIM: gene MIM:614154 | disease phenotypes: MIM:614153

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 36	Definitive	Autosomal dominant

Mondo (2): spinocerebellar ataxia type 36 (MONDO:0013594), cerebellar ataxia (MONDO:0000437)

Orphanet (2): Spinocerebellar ataxia type 36 (Orphanet:276198), Rare ataxia (Orphanet:102002)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000508	Ptosis
HP:0000511	Vertical supranuclear gaze palsy
HP:0000514	Slow saccadic eye movements
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002076	Migraine
HP:0002078	Truncal ataxia
HP:0002080	Intention tremor
HP:0002311	Incoordination
HP:0002321	Vertigo
HP:0002346	Head tremor
HP:0002378	Hand tremor
HP:0002380	Fasciculations
HP:0002607	Bowel incontinence

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066335 (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
5.40	Kd	4002	nM	CHEMBL5653589
5.40	ED50	4002	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148883: Binding affinity to human NOP56 incubated for 45 mins by Kinobead based pull down assay	kd	4.0019	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	increases expression, decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression	2
Estradiol	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression	2
Plant Extracts	increases expression, decreases expression, affects cotreatment	2
Tretinoin	decreases expression	2
Aflatoxin B1	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
bleomycetin	increases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	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	decreases expression	1
bisphenol B	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
LDN 193189	affects cotreatment, decreases 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
CHEMBL5651925	Binding	Binding affinity to human NOP56 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

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3FH	SCD36-1	Induced pluripotent stem cell	Male
CVCL_A3FI	SCD36-2	Induced pluripotent stem cell	Male
CVCL_A3FJ	SCD36-3	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	PHASE2/PHASE3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	PHASE1/PHASE2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	PHASE1/PHASE2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272	Not specified	COMPLETED	Fall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251	Not specified	COMPLETED	Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861	Not specified	COMPLETED	Autoimmunity in Neurologic Complications of Celiac Disease
NCT01037777	Not specified	COMPLETED	RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia