PRR7

Summary

PRR7 (proline rich 7, synaptic, HGNC:28130) is a protein-coding gene on chromosome 5q35.3, encoding Proline-rich protein 7 (Q8TB68). Acts as a synapse-to-nucleus messenger to promote NMDA receptor-mediated excitotoxicity in neurons in a JUN-dependent manner.

Enables long-chain fatty acid binding activity; protein tyrosine kinase binding activity; and ubiquitin-like protein ligase binding activity. Involved in positive regulation of apoptotic process and regulation of transcription by RNA polymerase I. Located in several cellular components, including cytosol; nucleoplasm; and perinuclear region of cytoplasm.

Source: NCBI Gene 80758 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_030567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28130
Approved symbol	PRR7
Name	proline rich 7, synaptic
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10772
Ensembl gene	ENSG00000131188
Ensembl biotype	protein_coding
OMIM	618306
Entrez	80758

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000323249, ENST00000502922, ENST00000507881, ENST00000510492, ENST00000861634, ENST00000861635, ENST00000861636, ENST00000961862

RefSeq mRNA: 5 — MANE Select: NM_030567 NM_001174101, NM_001174102, NM_001375593, NM_001375594, NM_030567

CCDS: CCDS4419

Canonical transcript exons

ENST00000323249 — 4 exons

Exon	Start	End
ENSE00001157409	177455724	177456286
ENSE00001225687	177453956	177454040
ENSE00001225745	177454829	177455494
ENSE00001316328	177446814	177446960

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 86.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2499 / max 195.3414, expressed in 1665 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60487	13.0591	1565
60495	1.4983	545
60491	0.9698	158
60489	0.8784	324
60485	0.8035	448
60493	0.6292	244
60486	0.4867	262
60492	0.2592	84
60488	0.2390	101
60484	0.1951	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	86.07	gold quality
caudate nucleus	UBERON:0001873	85.41	gold quality
putamen	UBERON:0001874	84.90	gold quality
cortical plate	UBERON:0005343	84.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.35	gold quality
right uterine tube	UBERON:0001302	83.25	gold quality
anterior cingulate cortex	UBERON:0009835	82.91	gold quality
cingulate cortex	UBERON:0003027	82.77	gold quality
right frontal lobe	UBERON:0002810	82.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.27	gold quality
amygdala	UBERON:0001876	82.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.47	gold quality
granulocyte	CL:0000094	79.43	gold quality
monocyte	CL:0000576	79.22	gold quality
mononuclear cell	CL:0000842	78.95	gold quality
Ammon’s horn	UBERON:0001954	78.86	gold quality
leukocyte	CL:0000738	78.74	gold quality
adenohypophysis	UBERON:0002196	78.51	gold quality
telencephalon	UBERON:0001893	77.96	gold quality
ventricular zone	UBERON:0003053	77.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.34	gold quality
forebrain	UBERON:0001890	77.33	gold quality
pituitary gland	UBERON:0000007	76.76	gold quality
cerebral cortex	UBERON:0000956	76.34	gold quality
neocortex	UBERON:0001950	75.77	gold quality
temporal lobe	UBERON:0001871	75.70	gold quality
brain	UBERON:0000955	75.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.63	gold quality
oocyte	CL:0000023	75.37	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting PRR7, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1972	97.67	67.38	1172

Literature-anchored findings (GeneRIF, showing 2)

• PRR7 is a potential regulator of signaling and apoptosis in activated T cells. (PMID:21460222)
• The authors find that PRR7 inhibits the ubiquitination of c-Jun by E3 ligase SCF(FBW) (7) (FBW7), increases c-Jun-dependent transcriptional activity, and promotes neuronal death. (PMID:27458189)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prr7	ENSMUSG00000034686
rattus_norvegicus	Prr7	ENSRNOG00000021447

Paralogs (2): WBP1L (ENSG00000166272), WBP1 (ENSG00000239779)

Protein

Protein identifiers

Proline-rich protein 7 — Q8TB68 (reviewed: Q8TB68)

Alternative names: Synaptic proline-rich membrane protein

All UniProt accessions (2): D6RFJ4, Q8TB68

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a synapse-to-nucleus messenger to promote NMDA receptor-mediated excitotoxicity in neurons in a JUN-dependent manner. Inhibits ubiquitination-mediated degradation and promotes phosphorylation and transcriptional activity of transcription factor JUN. Might play a redundant role in the regulation of T cell receptor signaling. Might promote apoptosis in T cells.

Subunit / interactions. Forms a complex with NMDA receptor zeta subunit GRIN1 and epsilon subunit GRIN2B. Interacts with GRIN1 and GRIN2B. The interaction with GRIN1 is reduced upon NMDA receptor activity. Found in a postsynaptic membrane complex with DLG4 and GRIN1. Interacts with DLG4 (via PDZ3 domain and to lesser degree via PDZ2 domain). Found in a complex with JUN and FBXW7. Interacts with JUN and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity. Interacts with SRC.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Postsynaptic density membrane. Cytoplasm. Perinuclear region. Synapse. Cell projection. Dendrite. Nucleus.

Tissue specificity. Strongly expressed in brain tissue including the hippocampus, and moderately expressed in esophagus, trachea, lung, ovary, cervix, prostate, testes, thyroid, thymus, lymph nodes and peripheral blood lymphocytes.

Post-translational modifications. Palmitoylated. Tyrosine phosphorylated, possibly by SRC.

Induction. Up-regulated in peripheral blood leukocytes in response to T-cell receptor stimulation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TB68-1	1	yes
Q8TB68-2	2

RefSeq proteins (5): NP_001167572, NP_001167573, NP_001362522, NP_001362523, NP_085044* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051994	WW_domain-binding	Family

UniProt features (22 total): mutagenesis site 6, region of interest 5, compositionally biased region 3, topological domain 2, chain 1, modified residue 1, splice variant 1, sequence variant 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB68-F1	56.84	0.10

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): 64

Mutagenesis-validated functional residues (6):

Position	Phenotype
139	reduced induction of apoptosis; when associated with f-153; f-166; f-177; f-201 and f-210.
153	reduced induction of apoptosis; when associated with f-139; f-166; f-177; f-201 and f-210.
166	reduced induction of apoptosis; when associated with f-139; f-153; f-177; f-201 and f-210.
177	reduced induction of apoptosis; when associated with f-139; f-153; f-166; f-201 and f-210.
201	reduced induction of apoptosis; when associated with f-139; f-153; f-166; f-177 and f-210.
210	reduced induction of apoptosis; when associated with f-139; f-153; f-166; f-177 and f-201.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GGTGTGT_MIR329, GCANCTGNY_MYOD_Q6, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, COUP_01, AP1_Q4_01, MYCMAX_01, TGTGTGA_MIR377, HNF4_DR1_Q3, TGANTCA_AP1_C, GOBP_ADAPTIVE_IMMUNE_RESPONSE, PPAR_DR1_Q2, GOBP_SYNAPTIC_SIGNALING, IRF_Q6

GO Biological Process (7): adaptive immune response (GO:0002250), regulation of transcription by RNA polymerase I (GO:0006356), T cell differentiation in thymus (GO:0033077), positive regulation of apoptotic process (GO:0043065), alpha-beta T cell differentiation (GO:0046632), postsynapse to nucleus signaling pathway (GO:0099527), immune system process (GO:0002376)

GO Molecular Function (5): long-chain fatty acid binding (GO:0036041), ubiquitin-like protein ligase binding (GO:0044389), protein-containing complex binding (GO:0044877), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), dendrite (GO:0030425), perinuclear region of cytoplasm (GO:0048471), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), cytoplasm (GO:0005737), postsynaptic density (GO:0014069), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
T cell differentiation	2
binding	2
cytoplasm	2
postsynaptic density	2
immune response	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase I	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
alpha-beta T cell activation	1
postsynaptic signal transduction	1
biological_process	1
fatty acid binding	1
enzyme binding	1
protein kinase binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
synapse	1
postsynaptic specialization, intracellular component	1
intracellular anatomical structure	1
asymmetric synapse	1
postsynaptic specialization	1
plasma membrane bounded cell projection	1
cell junction	1
synaptic membrane	1
postsynapse	1

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRR7	PRR9	Q5T870	871
PRR7	PRR5	P85299	671
PRR7	ELF4	Q99607	622
PRR7	TRNT1	Q96Q11	582
PRR7	FAM193B	Q96PV7	498
PRR7	LMAN2	Q12907	462
PRR7	LTC4S	Q16873	455
PRR7	TRIM52	Q96A61	449
PRR7	POLR3E	Q9NVU0	444
PRR7	B4GALT7	Q9UBV7	435
PRR7	CHPT1	Q8WUD6	424
PRR7	ELF3	P78545	418
PRR7	TMED9	Q9BVK6	410
PRR7	FAF2	Q96CS3	408
PRR7	NYAP2	Q9P242	407

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NEDD4	PRR7	psi-mi:“MI:0407”(direct interaction)	0.590
YAP1	PRR7	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF785	PRR7	psi-mi:“MI:0915”(physical association)	0.370
NEDD4	PRRG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): PRR7 (Affinity Capture-RNA), PRR7 (Affinity Capture-MS), PRR7 (Protein-peptide), PRR7 (Protein-peptide), PRR7 (Affinity Capture-RNA), ZNF785 (Two-hybrid)

ESM2 similar proteins: A0A8I3QA39, A2A699, A2A9T0, A2AEV7, A2AHG0, A2AJA9, A5PKL7, A6NKL6, A6NL88, A6QPA0, A7MCY6, A8MVW0, B8ZZ34, C9J069, E9Q1P8, F1MRK3, J3QNX5, O60299, P0C7U0, Q02779, Q15742, Q2M3V2, Q3LUD4, Q3UH99, Q3V0I2, Q5BJT1, Q5BJU3, Q5HZI2, Q61127, Q66L44, Q69YU3, Q6DG50, Q6ZRV2, Q6ZSJ9, Q7Z5L9, Q8BLS7, Q8C3Q5, Q8C8T7, Q8IX07, Q8IZD0

Diamond homologs: P0C6T3, Q3V0I2, Q8TB68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

660 predictions. Top by Δscore:

Variant	Effect	Δscore
5:177446956:GGCCC:G	donor_gain	1.0000
5:177446957:GCCC:G	donor_gain	1.0000
5:177446957:GCCCG:G	donor_gain	1.0000
5:177446961:G:GG	donor_gain	1.0000
5:177446945:G:GT	donor_gain	0.9900
5:177446958:CCC:C	donor_gain	0.9900
5:177446959:CC:C	donor_gain	0.9900
5:177446959:CCGT:C	donor_loss	0.9900
5:177446960:CG:C	donor_loss	0.9900
5:177446961:G:T	donor_loss	0.9900
5:177446962:T:G	donor_loss	0.9900
5:177446963:GAG:G	donor_loss	0.9900
5:177446964:AGT:A	donor_loss	0.9900
5:177455722:A:AG	acceptor_gain	0.9800
5:177455722:AGC:A	acceptor_gain	0.9800
5:177455723:G:GG	acceptor_gain	0.9800
5:177455723:GCG:G	acceptor_gain	0.9800
5:177446948:G:GT	donor_gain	0.9700
5:177446965:G:C	donor_loss	0.9700
5:177455722:AGCG:A	acceptor_gain	0.9700
5:177455723:GCGG:G	acceptor_gain	0.9700
5:177446964:A:AG	donor_gain	0.9600
5:177446965:G:GG	donor_gain	0.9600
5:177455723:GC:G	acceptor_gain	0.9600
5:177455723:GCGGA:G	acceptor_gain	0.9600
5:177455755:CGAAG:C	acceptor_gain	0.9200
5:177455492:AAGGT:A	donor_loss	0.9000
5:177455493:AGGTG:A	donor_loss	0.9000
5:177455494:GGTG:G	donor_loss	0.9000
5:177455495:G:T	donor_loss	0.9000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000411522 (5:177446552 T>C), RS1000698031 (5:177447773 C>G), RS1000986634 (5:177454742 C>A,T), RS1001025642 (5:177447663 T>C), RS1001563063 (5:177448026 C>A), RS1001826343 (5:177444716 C>G,T), RS1001927966 (5:177453688 C>T), RS1001959095 (5:177453431 C>T), RS1002227560 (5:177451248 T>C), RS1002258811 (5:177450963 G>C), RS1002900547 (5:177448682 C>T), RS1002921709 (5:177448248 G>T), RS1002960789 (5:177451343 G>A), RS1003090015 (5:177446022 T>C), RS1003239010 (5:177450020 C>T)

Disease associations

OMIM: gene MIM:618306 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000649_23	Chronic kidney disease	1.000000e-14
GCST001574_7	Activated partial thromboplastin time	6.000000e-88
GCST005956_15	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-07
GCST005962_42	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST007044_13	Extremely high intelligence	3.000000e-08
GCST007576_172	Chronotype	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004337	intelligence
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	5
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases 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
picoxystrobin	decreases expression	1
MT19c compound	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	1
Quercetin	increases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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