PRND

Summary

PRND (prion like protein doppel, HGNC:15748) is a protein-coding gene on chromosome 20p13, encoding Prion-like protein doppel (Q9UKY0). Required for normal acrosome reaction and for normal male fertility.

This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders.

Source: NCBI Gene 23627 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_012409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15748
Approved symbol	PRND
Name	prion like protein doppel
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	DPL, dJ1068H6.4, DOPPEL, PrPLP
Ensembl gene	ENSG00000171864
Ensembl biotype	protein_coding
OMIM	604263
Entrez	23627

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000305817

RefSeq mRNA: 1 — MANE Select: NM_012409 NM_012409

CCDS: CCDS13081

Canonical transcript exons

ENST00000305817 — 2 exons

Exon	Start	End
ENSE00001161332	4724541	4728460
ENSE00001333363	4721909	4721969

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 95.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5838 / max 265.1029, expressed in 58 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183305	0.5838	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	95.04	gold quality
left testis	UBERON:0004533	94.19	gold quality
adult organism	UBERON:0007023	93.08	gold quality
testis	UBERON:0000473	93.03	gold quality
choroid plexus epithelium	UBERON:0003911	91.98	gold quality
visceral pleura	UBERON:0002401	81.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.35	gold quality
buccal mucosa cell	CL:0002336	72.01	gold quality
pleura	UBERON:0000977	71.41	gold quality
skin of hip	UBERON:0001554	66.65	gold quality
parietal pleura	UBERON:0002400	65.51	silver quality
body of uterus	UBERON:0009853	61.74	gold quality
gall bladder	UBERON:0002110	61.00	gold quality
myometrium	UBERON:0001296	60.59	gold quality
smooth muscle tissue	UBERON:0001135	59.76	gold quality
ganglionic eminence	UBERON:0004023	59.04	gold quality
tibialis anterior	UBERON:0001385	58.72	silver quality
cerebellar vermis	UBERON:0004720	58.36	gold quality
ileal mucosa	UBERON:0000331	57.08	silver quality
upper leg skin	UBERON:0004262	56.97	silver quality
pancreatic ductal cell	CL:0002079	56.71	silver quality
hair follicle	UBERON:0002073	56.68	gold quality
decidua	UBERON:0002450	56.55	gold quality
deltoid	UBERON:0001476	55.36	gold quality
uterus	UBERON:0000995	55.03	gold quality
embryo	UBERON:0000922	54.47	gold quality
cranial nerve II	UBERON:0000941	53.28	silver quality
endometrium	UBERON:0001295	52.51	gold quality
epithelial cell of pancreas	CL:0000083	52.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	51.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU4F1, SP1, SP3, USF1

miRNA regulators (miRDB)

121 targeting PRND, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-5696	99.98	72.36	4487
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-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6780A-5P	99.88	66.69	2776

Literature-anchored findings (GeneRIF, showing 16)

• expression pattern and biochemical characteristics in human tissues and in Chinese hamster ovary cells transfected with wild-type or variant human Dpl gene constructs (PMID:12200435)
• Doppel expression is not modified in the brains of patients with Creutzfeldt-Jakob disease. (PMID:12586339)
• human Doppel fails to interact with itself; Dpl and PrP are not related or are only marginally related with respect to their ligand binding behaviour (PMID:15158907)
• results demonstrate that Doppel and PrPc co-patch extensively at the plasma membrane (PMID:15203115)
• Doppel interacts with the full-length laminin receptor precursor protein (PMID:15246873)
• Doppel is expressed early during ontogenesis, and is found in both germ cells and Sertoli cells. Doppel may play a physiological role in acrosome biogenesis. (PMID:16421231)
• Dpl interacts with RACK1 by means of its structured globular carboxyl-terminal region (PMID:17201176)
• Extensive differences in PRND gene expression were also found within each grade of malignancy, suggesting that PRND mRNA quantitation might be useful to distinguish astrocytoma subtypes. (PMID:17390034)
• Study provides the foundation for further study of Dpl biological functions in vitro and in vivo. (PMID:17894227)
• Results might suggest a potential and functional role for Dpl in tumor cells migratory and morphological behaviours and address to future gene-targeted therapeutic interventions. (PMID:18936526)
• results suggested that the function of Dpl is antagonistic to PrP rather than synergistic (PMID:19129949)
• From the logistic regression ananlsis of this stidy showed that the highest risk for was found for Alzheimer’s disease individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. (PMID:19363267)
• Cytotoxicity induced by the expression of Dpl and truncated PrP in neural derived cells are closely related with the apoptosis process. (PMID:19728151)
• in astrocytomas, Dpl undergoes different molecular processes that might constitute additional helpful tools to characterize the glial tumor progression (PMID:20981146)
• The association between the APOE, CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with Alzheimer’s disease and mild cognitive impairment, was evaluated. (PMID:22453181)
• results demonstrate that blocking doppel can control VEGF signaling in TECs and selectively inhibit tumor angiogenesis. (PMID:26950422)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prnd	ENSMUSG00000027338
rattus_norvegicus	Prnd	ENSRNOG00000021260

Protein

Protein identifiers

Prion-like protein doppel — Q9UKY0 (reviewed: Q9UKY0)

Alternative names: PrPLP, Prion protein 2

All UniProt accessions (1): Q9UKY0

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal acrosome reaction and for normal male fertility. Can bind Cu(2+).

Subcellular location. Cell membrane.

Tissue specificity. Expressed in testis, in Sertoli cells, ejaculated spermatozoa and in seminal fluid (at protein level).

Post-translational modifications. N-glycosylated. N-glycosylated at two distinct sites. O-glycosylated.

Domain organisation. A short helical region is required and sufficient for Cu(2+) binding.

Similarity. Belongs to the prion family.

RefSeq proteins (1): NP_036541* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021566	Doppel	Family
IPR022416	Prion/Doppel_prot_b-ribbon_dom	Domain
IPR036924	Prion/Doppel_b-ribbon_dom_sf	Homologous_superfamily

Pfam: PF00377, PF11466

UniProt features (27 total): sequence variant 8, helix 4, region of interest 3, glycosylation site 3, disulfide bond 2, signal peptide 1, chain 1, propeptide 1, sequence conflict 1, turn 1, strand 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1LG4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKY0-F1	77.10	0.39

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): 152

Disulfide bonds (2): 94–145, 108–140

Glycosylation sites (3): 43, 98, 110

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 98 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_CELL_SURFACE, GOBP_RESPONSE_TO_COPPER_ION, CHX10_01, GOBP_RESPONSE_TO_METAL_ION, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_ACROSOME_REACTION, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_COPPER_ION_HOMEOSTASIS, GOBP_FERTILIZATION, DELASERNA_MYOD_TARGETS_UP, GOBP_HOMEOSTATIC_PROCESS, GOCC_SIDE_OF_MEMBRANE, GOBP_CHEMICAL_HOMEOSTASIS

GO Biological Process (4): intracellular copper ion homeostasis (GO:0006878), acrosome reaction (GO:0007340), protein homooligomerization (GO:0051260), single fertilization (GO:0007338)

GO Molecular Function (3): copper ion binding (GO:0005507), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
intracellular monoatomic cation homeostasis	1
copper ion homeostasis	1
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
protein complex oligomerization	1
fertilization	1
transition metal ion binding	1
binding	1
cation binding	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRND	PRNP	P04156	951
PRND	SPRN	Q5BIV9	881
PRND	TRIB3	Q96RU7	769
PRND	PDYN	P01213	657
PRND	PRR4	Q16378	608
PRND	MSMB	P08118	507
PRND	PACC1	Q9H813	460
PRND	RASSF2	P50749	438
PRND	MTG1	Q9BT17	429
PRND	PDIA3	P30101	423
PRND	SUOX	P51687	393
PRND	KDR	P35968	390
PRND	MAPK15	Q8TD08	386
PRND	KIAA1210	Q9ULL0	377
PRND	CCER2	I3L3R5	365

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TREX1	PRND	psi-mi:“MI:0915”(physical association)	0.560
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
PRND	ATP1A3	psi-mi:“MI:0914”(association)	0.350
TREX1	PRND	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): PRND (Affinity Capture-MS), TREX1 (Two-hybrid), RSPRY1 (Affinity Capture-MS), CALHM2 (Affinity Capture-MS), AGPAT5 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D9SF12, A0A1B0GTR0, A0JNN2, A6H7F9, D3ZKM3, E1C7U0, E9PXB6, F5HCP3, F5HFJ7, P01586, P03212, P04823, P06740, P08700, P09728, P14355, P14683, P16772, P28907, P35771, P51748, P68980, P68981, Q1HVF6, Q1JQE1, Q1ZYL8, Q28809, Q29118, Q2TAV2, Q3KSS3, Q5BK38, Q5JX69, Q5RBQ2, Q5U2R2, Q5VAN0, Q60481, Q68FB2, Q6P4J6, Q6UW10, Q6UWF9

Diamond homologs: Q9GJY2, Q9GK16, Q9QUG3, Q9UKY0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

133 predictions. Top by Δscore:

Variant	Effect	Δscore
20:4724536:GGCA:G	acceptor_loss	1.0000
20:4724537:GCA:G	acceptor_loss	1.0000
20:4724538:CAGGT:C	acceptor_loss	1.0000
20:4724539:AGGT:A	acceptor_loss	1.0000
20:4724540:G:GA	acceptor_loss	1.0000
20:4721968:AGG:A	donor_loss	0.9900
20:4721970:GTAC:G	donor_loss	0.9900
20:4724539:A:AG	acceptor_gain	0.9900
20:4724540:G:GG	acceptor_gain	0.9900
20:4721971:T:G	donor_loss	0.9800
20:4724535:T:TA	acceptor_gain	0.9800
20:4724539:AG:A	acceptor_gain	0.9800
20:4724540:GG:G	acceptor_gain	0.9800
20:4724540:GGTT:G	acceptor_gain	0.9800
20:4724540:GGTTC:G	acceptor_gain	0.9800
20:4724536:G:A	acceptor_gain	0.9700
20:4724540:GGT:G	acceptor_gain	0.9700
20:4721970:G:GG	donor_gain	0.9500
20:4724233:GTAT:G	acceptor_gain	0.9500
20:4724234:TATT:T	acceptor_gain	0.9500
20:4724235:ATTA:A	acceptor_gain	0.9500
20:4724236:T:TG	acceptor_gain	0.9100
20:4721968:AG:A	donor_gain	0.9000
20:4721969:GG:G	donor_gain	0.9000
20:4721965:CCAAG:C	donor_gain	0.8300
20:4721967:AAG:A	donor_gain	0.8300
20:4724236:T:G	donor_gain	0.8200
20:4724945:C:CG	donor_gain	0.7700
20:4721966:CAAG:C	donor_gain	0.7500
20:4724232:T:G	acceptor_gain	0.7300

AlphaMissense

1163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:4724873:T:A	C108S	0.979
20:4724874:G:C	C108S	0.979
20:4724727:T:G	F59C	0.978
20:4724727:T:C	F59S	0.974
20:4724808:C:A	P86H	0.974
20:4724971:C:G	C140W	0.974
20:4724726:T:C	F59L	0.970
20:4724728:C:A	F59L	0.970
20:4724728:C:G	F59L	0.970
20:4724805:T:C	F85S	0.967
20:4724817:T:C	I89T	0.966
20:4724873:T:C	C108R	0.966
20:4724875:C:G	C108W	0.965
20:4724955:T:C	L135P	0.964
20:4724970:G:A	C140Y	0.964
20:4724969:T:C	C140R	0.961
20:4724874:G:A	C108Y	0.958
20:4724969:T:A	C140S	0.957
20:4724970:G:C	C140S	0.957
20:4724817:T:G	I89S	0.955
20:4724808:C:G	P86R	0.953
20:4724783:T:G	Y78D	0.952
20:4724817:T:A	I89N	0.946
20:4724800:G:C	W83C	0.942
20:4724800:G:T	W83C	0.942
20:4724760:T:C	F70S	0.941
20:4724882:G:C	A111P	0.939
20:4724967:T:C	L139P	0.938
20:4724720:G:A	G57R	0.936
20:4724720:G:C	G57R	0.936

dbSNP variants (sampled 300 via entrez): RS1000452062 (20:4722105 A>T), RS1000514564 (20:4721946 A>C), RS1000759653 (20:4726928 G>A), RS1001139187 (20:4723955 T>G), RS1001379302 (20:4724281 A>G), RS1002199675 (20:4723332 T>C), RS1002536157 (20:4723064 C>T), RS1002856713 (20:4725367 A>C,G), RS1002922295 (20:4720938 C>T), RS1002994508 (20:4721191 T>A,C), RS1003236339 (20:4725222 C>T), RS1003728564 (20:4728935 T>A), RS1004140605 (20:4720559 A>G), RS1004381319 (20:4722529 T>C), RS1004427072 (20:4728667 A>C,G)

Disease associations

OMIM: gene MIM:604263 | 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
GCST007897_2	Liver injury in anti-tuberculosis drug treatment	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007918	response to anti-tuberculosis drug

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Valproic Acid	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Silicon Dioxide	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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