SPRN

Summary

SPRN (shadow of prion protein, HGNC:16871) is a protein-coding gene on chromosome 10q26.3, encoding Shadow of prion protein (Q5BIV9). Prion-like protein that has PrP(C)-like neuroprotective activity.

Predicted to enable nucleic acid binding activity. Predicted to be involved in protein import into nucleus. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in nucleus.

Source: NCBI Gene 503542 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_001391974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16871
Approved symbol	SPRN
Name	shadow of prion protein
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	Shadoo, bA108K14.1, FLJ41197
Ensembl gene	ENSG00000203772
Ensembl biotype	protein_coding
OMIM	610447
Entrez	503542

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000414069, ENST00000685335, ENST00000949115

RefSeq mRNA: 2 — MANE Select: NM_001391974 NM_001012508, NM_001391974

CCDS: CCDS53589

Canonical transcript exons

ENST00000685335 — 2 exons

Exon	Start	End
ENSE00001741790	133420666	133423697
ENSE00003934024	133424473	133424625

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 92.12.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	92.12	gold quality
cortical plate	UBERON:0005343	83.73	gold quality
right frontal lobe	UBERON:0002810	83.69	gold quality
prefrontal cortex	UBERON:0000451	81.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.47	gold quality
frontal cortex	UBERON:0001870	79.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.72	gold quality
anterior cingulate cortex	UBERON:0009835	78.67	gold quality
neocortex	UBERON:0001950	78.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.92	gold quality
cerebellar hemisphere	UBERON:0002245	77.91	gold quality
cerebellar cortex	UBERON:0002129	77.90	gold quality
buccal mucosa cell	CL:0002336	77.30	silver quality
cerebellum	UBERON:0002037	76.66	gold quality
cerebral cortex	UBERON:0000956	75.46	gold quality
tendon of biceps brachii	UBERON:0008188	75.13	gold quality
epithelial cell of pancreas	CL:0000083	71.40	silver quality
amygdala	UBERON:0001876	70.93	gold quality
forebrain	UBERON:0001890	70.93	gold quality
brain	UBERON:0000955	70.91	gold quality
kidney epithelium	UBERON:0004819	70.54	gold quality
Ammon’s horn	UBERON:0001954	70.10	gold quality
nucleus accumbens	UBERON:0001882	69.76	gold quality
primary visual cortex	UBERON:0002436	69.55	gold quality
superior frontal gyrus	UBERON:0002661	68.58	gold quality
nasal cavity epithelium	UBERON:0005384	68.51	gold quality
myocardium	UBERON:0002349	68.47	gold quality
upper leg skin	UBERON:0004262	68.22	silver quality
ganglionic eminence	UBERON:0004023	68.14	gold quality
caudate nucleus	UBERON:0001873	68.12	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting SPRN, 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-4283	100.00	66.42	2097
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6756-5P	99.82	67.97	2466

Literature-anchored findings (GeneRIF, showing 4)

• A novel solid phase technology for high- throughput synthesis of the SPRN gene is reported. (PMID:18778261)
• Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease (PMID:18805828)
• a conserved physiological activity between PrP(C) and Sho to protect cells from stress-induced toxicity and suggests that Sho and PrP(C) might act on similar signaling pathways. (PMID:21257747)
• Shadoo is degraded in Scrapie-infected rodents and cultured cells mediated by proteasome degradation after modification by ubiquitination. (PMID:24390475)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sprn	ENSMUSG00000045733
rattus_norvegicus	Sprn	ENSRNOG00000067971

Protein

Protein identifiers

Shadow of prion protein — Q5BIV9 (reviewed: Q5BIV9)

All UniProt accessions (1): Q5BIV9

UniProt curated annotations — full annotation on UniProt →

Function. Prion-like protein that has PrP(C)-like neuroprotective activity. May act as a modulator for the biological actions of normal and abnormal PrP.

Subcellular location. Cell membrane.

Tissue specificity. Mainly expressed in brain. In brain, it is expressed in hippocampus.

Post-translational modifications. N-glycosylated.

Miscellaneous. ‘Shadoo’ means ‘shadow’ in Japanese.

Similarity. Belongs to the SPRN family.

RefSeq proteins (2): NP_001012526, NP_001378903* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029238	Shadoo	Family

Pfam: PF14999

UniProt features (7 total): signal peptide 1, chain 1, propeptide 1, region of interest 1, lipid moiety-binding region 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5BIV9-F1	54.62	0.00

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 (1): 126

Glycosylation sites (1): 111

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 52 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOCC_SIDE_OF_MEMBRANE, GOCC_NUCLEOLUS, MORF_CDC2L5, CACTGCC_MIR34A_MIR34C_MIR449, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, GOBP_INTRACELLULAR_TRANSPORT, GOBP_IMPORT_INTO_NUCLEUS, REACTOME_POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS, MIR4492

GO Biological Process (1): protein import into nucleus (GO:0006606)

GO Molecular Function (1): nucleic acid binding (GO:0003676)

GO Cellular Component (8): extracellular region (GO:0005576), nucleus (GO:0005634), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), vesicle (GO:0031982), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
cell periphery	1
membrane-bounded organelle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRN	MTG1	Q9BT17	966
SPRN	PRND	Q9UKY0	881
SPRN	PRNP	P04156	877
SPRN	GTPBP4	Q9BZE4	715
SPRN	SYCE1	Q8N0S2	507
SPRN	AP5S1	Q9NUS5	507
SPRN	CALR	P27797	489
SPRN	ECHS1	P30084	474
SPRN	MSMB	P08118	470
SPRN	CYP2E1	P05181	394
SPRN	PRR4	Q16378	366
SPRN	RASSF2	P50749	357
SPRN	STIP1	P31948	322
SPRN	STK35	Q8TDR2	322
SPRN	CD24	P25063	291

IntAct

2 interactions, top by confidence:

A	B	Type	Score
STRN4	SPRN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): SPRN (Affinity Capture-RNA)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: A0RZB4, A6XN32, Q5BIV7, Q5BIV9, Q8BWU1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

310 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133423693:TAAAC:T	acceptor_gain	1.0000
10:133423699:T:A	acceptor_loss	1.0000
10:133424469:TTACC:T	donor_loss	1.0000
10:133424470:TA:T	donor_loss	1.0000
10:133424471:AC:A	donor_gain	1.0000
10:133424472:C:CA	donor_loss	1.0000
10:133424472:CC:C	donor_gain	1.0000
10:133423698:C:CC	acceptor_gain	0.9900
10:133424471:A:AC	donor_gain	0.9900
10:133424471:ACCCG:A	donor_gain	0.9900
10:133424472:C:CC	donor_gain	0.9900
10:133424472:CCCG:C	donor_gain	0.9900
10:133424472:CCCGC:C	donor_gain	0.9900
10:133423694:AAAC:A	acceptor_gain	0.9800
10:133423695:AAC:A	acceptor_gain	0.9800
10:133423696:AC:A	acceptor_gain	0.9800
10:133423697:CC:C	acceptor_gain	0.9800
10:133423696:ACCT:A	acceptor_gain	0.9700
10:133423697:CCTGC:C	acceptor_gain	0.9700
10:133423694:AAACC:A	acceptor_gain	0.9600
10:133423695:AACC:A	acceptor_gain	0.9600
10:133423698:CTGC:C	acceptor_gain	0.9600
10:133424471:ACC:A	donor_gain	0.9600
10:133424472:CCC:C	donor_gain	0.9600
10:133423702:G:T	acceptor_gain	0.9500
10:133423877:AGG:A	donor_gain	0.9500
10:133423595:T:TA	donor_gain	0.9400
10:133423699:T:G	acceptor_gain	0.9100
10:133424515:C:A	donor_gain	0.9100
10:133424482:G:A	donor_gain	0.9000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000775826 (10:133421134 G>GGTGCTCAGTGGCCCCTC), RS1000959523 (10:133422970 T>C), RS1001560331 (10:133422150 G>A), RS1003431369 (10:133422215 C>T), RS1004163514 (10:133425449 A>G), RS1004484473 (10:133421600 T>C), RS1004616620 (10:133421929 C>T), RS1004788683 (10:133421402 T>G), RS1005331123 (10:133426223 T>C), RS1005798396 (10:133420337 C>T), RS1006744719 (10:133423315 A>G), RS1006746515 (10:133423475 G>A,C,T), RS1007749272 (10:133422688 A>C), RS1007778516 (10:133422883 G>A,C), RS1007835281 (10:133423908 T>G)

Disease associations

OMIM: gene MIM:610447 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST011125_20	Caffeine consumption from coffee	1.000000e-08
GCST011126_21	Caffeine consumption from coffee or tea	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
cobaltous chloride	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	decreases phosphorylation	1
Lead	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Dronabinol	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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