TPRG1L

Summary

TPRG1L (tumor protein p63 regulated 1 like, HGNC:27007) is a protein-coding gene on chromosome 1p36.32, encoding Tumor protein p63-regulated gene 1-like protein (Q5T0D9). Presynaptic protein involved in the synaptic transmission tuning.

Predicted to enable calmodulin binding activity and identical protein binding activity. Predicted to be involved in presynaptic modulation of chemical synaptic transmission; regulation of glutamatergic synaptic transmission; and regulation of synaptic vesicle exocytosis. Predicted to act upstream of or within calcineurin-NFAT signaling cascade; negative regulation of synaptic transmission; and synaptic vesicle docking. Located in extracellular exosome.

Source: NCBI Gene 127262 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total — 1 pathogenic
• MANE Select transcript: NM_182752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27007
Approved symbol	TPRG1L
Name	tumor protein p63 regulated 1 like
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	RP11-46F15.3, FLJ21811, TPRGL, SVAP30, h-Mover
Ensembl gene	ENSG00000158109
Ensembl biotype	protein_coding
OMIM	611460
Entrez	127262

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000344579, ENST00000378344, ENST00000888361

RefSeq mRNA: 1 — MANE Select: NM_182752 NM_182752

CCDS: CCDS47

Canonical transcript exons

ENST00000378344 — 5 exons

Exon	Start	End
ENSE00001037055	3625424	3625515
ENSE00001037059	3627500	3627653
ENSE00001367613	3625713	3625889
ENSE00001904186	3628409	3630127
ENSE00001913075	3625015	3625273

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6560 / max 136.2087, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
300	20.6560	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.98	gold quality
kidney epithelium	UBERON:0004819	97.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.22	gold quality
right frontal lobe	UBERON:0002810	96.87	gold quality
anterior cingulate cortex	UBERON:0009835	96.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.47	gold quality
prefrontal cortex	UBERON:0000451	96.42	gold quality
nucleus accumbens	UBERON:0001882	96.08	gold quality
frontal cortex	UBERON:0001870	96.03	gold quality
tibialis anterior	UBERON:0001385	95.91	gold quality
caudate nucleus	UBERON:0001873	95.60	gold quality
neocortex	UBERON:0001950	95.57	gold quality
putamen	UBERON:0001874	95.39	gold quality
islet of Langerhans	UBERON:0000006	95.37	gold quality
hypothalamus	UBERON:0001898	95.35	gold quality
upper arm skin	UBERON:0004263	95.31	gold quality
mucosa of transverse colon	UBERON:0004991	95.16	gold quality
amygdala	UBERON:0001876	95.15	gold quality
cerebral cortex	UBERON:0000956	94.94	gold quality
superior frontal gyrus	UBERON:0002661	94.77	gold quality
right lobe of liver	UBERON:0001114	94.69	gold quality
forebrain	UBERON:0001890	94.61	gold quality
Ammon’s horn	UBERON:0001954	94.37	gold quality
rectum	UBERON:0001052	94.29	gold quality
gingiva	UBERON:0001828	94.14	gold quality
stromal cell of endometrium	CL:0002255	94.11	gold quality
temporal lobe	UBERON:0001871	94.09	gold quality
gingival epithelium	UBERON:0001949	94.08	gold quality
popliteal artery	UBERON:0002250	94.08	gold quality
tibial artery	UBERON:0007610	94.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting TPRG1L, 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-6778-3P	99.96	67.29	2693
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6715B-5P	99.64	69.63	1420

Literature-anchored findings (GeneRIF, showing 1)

• mover may act in concert with generally expressed scaffolding proteins in distinct sets of presynaptic terminals (PMID:17869247)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tprg1l	ENSDARG00000068149
mus_musculus	Tprg1l	ENSMUSG00000029030
rattus_norvegicus	Tprg1l	ENSRNOG00000046227

Paralogs (1): TPRG1 (ENSG00000188001)

Protein

Protein identifiers

Tumor protein p63-regulated gene 1-like protein — Q5T0D9 (reviewed: Q5T0D9)

Alternative names: Mossy fiber terminal-associated vertebrate-specific presynaptic protein, Protein FAM79A

All UniProt accessions (2): B4DPH8, Q5T0D9

UniProt curated annotations — full annotation on UniProt →

Function. Presynaptic protein involved in the synaptic transmission tuning. Regulates synaptic release probability by decreasing the calcium sensitivity of release.

Subunit / interactions. Forms homomultimers. Multimerization appears to be important for presynaptic targeting. Interacts with BSN.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Presynaptic active zone.

Post-translational modifications. Phosphorylated. Phosphorylation promotes association with synaptic vesicle membranes.

Similarity. Belongs to the TPRG1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T0D9-1	1	yes
Q5T0D9-2	2

RefSeq proteins (1): NP_877429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022158	Inositol_phosphatase	Domain
IPR034753	hSac2	Domain
IPR040242	TPRG1-like	Family

Pfam: PF12456

UniProt features (8 total): modified residue 3, region of interest 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T0D9-F1	71.89	0.24

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 (3): 10, 14, 40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_EXOCYTOSIS, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_SYNAPTIC_SIGNALING, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (4): obsolete synaptic vesicle docking (GO:0016081), calcineurin-NFAT signaling cascade (GO:0033173), negative regulation of synaptic transmission (GO:0050805), regulation of synaptic transmission, glutamatergic (GO:0051966)

GO Molecular Function (2): calmodulin binding (GO:0005516), identical protein binding (GO:0042802)

GO Cellular Component (11): cytoplasm (GO:0005737), synaptic vesicle (GO:0008021), synaptic vesicle membrane (GO:0030672), calyx of Held (GO:0044305), presynaptic active zone (GO:0048786), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
modulation of chemical synaptic transmission	2
protein binding	2
presynapse	2
calcineurin-mediated signaling	1
chemical synaptic transmission	1
negative regulation of cell communication	1
negative regulation of signaling	1
synaptic transmission, glutamatergic	1
intracellular anatomical structure	1
exocytic vesicle	1
synaptic vesicle	1
exocytic vesicle membrane	1
axon terminus	1
extracellular vesicle	1
cytoplasm	1
intracellular vesicle	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPRG1L	SYP	P08247	548
TPRG1L	WRAP73	Q9P2S5	541
TPRG1L	SEC23B	Q15437	504
TPRG1L	LIN37	Q96GY3	490
TPRG1L	ARHGEF16	Q5VV41	471
TPRG1L	ABCF1	Q8NE71	445
TPRG1L	DDX51	Q8N8A6	428
TPRG1L	CCDC27	Q2M243	419
TPRG1L	HAPLN4	Q86UW8	418
TPRG1L	DDX5	P17844	398
TPRG1L	SLC26A1	Q9H2B4	388
TPRG1L	GPR153	Q6NV75	377
TPRG1L	C1orf174	Q8IYL3	370
TPRG1L	TRAPPC13	A5PLN9	361
TPRG1L	ST7	Q9NRC1	359

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MLH1	TPRG1L	psi-mi:“MI:0915”(physical association)	0.370
TPRG1L	CCT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): TPRG1L (Affinity Capture-MS), CCT2 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), TPRG1L (Reconstituted Complex), TPRG1L (Two-hybrid), TPRG1L (Affinity Capture-RNA)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A1A535, A2BID5, A8E7C5, A8WCF8, B3MJV4, B4JE52, D3YVL2, F1QJX5, G3X9J0, O43147, Q08DX0, Q0VA04, Q12769, Q14D04, Q23658, Q2HJE1, Q2NKQ1, Q32LJ4, Q3V0G7, Q4G017, Q5JWR5, Q5PQS3, Q5T0D9, Q5U430, Q60PC0, Q61QK6, Q6NLL1, Q6TNU3, Q6ZT12, Q6ZUI0, Q7Z3E5, Q80TM9, Q80U12, Q8BL99, Q8BMQ2, Q8BPQ7, Q8CB49, Q8CDA1

Diamond homologs: A8WCF8, Q32LJ4, Q5T0D9, Q6ZUI0, Q8CB49, Q9DBS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
150566	GRCh38/hg38 1p36.33-36.31(chr1:844353-6477474)x1	Pathogenic

SpliceAI

560 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3625255:G:GT	donor_gain	1.0000
1:3625406:A:AG	acceptor_gain	1.0000
1:3625406:ACCCC:A	acceptor_gain	1.0000
1:3625407:C:G	acceptor_gain	1.0000
1:3625410:C:A	acceptor_gain	1.0000
1:3625413:A:AG	acceptor_gain	1.0000
1:3625413:AACCC:A	acceptor_gain	1.0000
1:3625414:A:G	acceptor_gain	1.0000
1:3625496:G:GT	donor_gain	1.0000
1:3625514:GA:G	donor_gain	1.0000
1:3625516:G:GG	donor_gain	1.0000
1:3625707:CTACA:C	acceptor_loss	1.0000
1:3625708:TACA:T	acceptor_loss	1.0000
1:3625710:CA:C	acceptor_loss	1.0000
1:3625711:A:AG	acceptor_gain	1.0000
1:3625711:A:AT	acceptor_loss	1.0000
1:3625711:AG:A	acceptor_gain	1.0000
1:3625712:G:C	acceptor_loss	1.0000
1:3625712:G:GG	acceptor_gain	1.0000
1:3625712:GG:G	acceptor_gain	1.0000
1:3625886:ACAA:A	donor_gain	1.0000
1:3625887:CAAG:C	donor_loss	1.0000
1:3625889:AG:A	donor_loss	1.0000
1:3625890:G:GG	donor_gain	1.0000
1:3625891:T:G	donor_loss	1.0000
1:3627489:T:TA	acceptor_gain	1.0000
1:3627498:A:AG	acceptor_gain	1.0000
1:3627499:G:GG	acceptor_gain	1.0000
1:3627499:GGC:G	acceptor_gain	1.0000
1:3627654:G:GA	donor_loss	1.0000

AlphaMissense

1758 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3625723:T:A	W102R	0.999
1:3625723:T:C	W102R	0.999
1:3625728:C:A	N103K	0.999
1:3625728:C:G	N103K	0.999
1:3627520:G:C	R164P	0.999
1:3627564:T:A	W179R	0.999
1:3627564:T:C	W179R	0.999
1:3625509:T:C	L96P	0.998
1:3625725:G:C	W102C	0.998
1:3625725:G:T	W102C	0.998
1:3625742:G:C	R108P	0.998
1:3625769:T:C	L117P	0.998
1:3625772:T:C	L118P	0.998
1:3625862:T:C	F148S	0.998
1:3625502:T:A	W94R	0.997
1:3625502:T:C	W94R	0.997
1:3625506:T:C	L95P	0.997
1:3625745:T:C	L109P	0.997
1:3625783:T:G	Y122D	0.997
1:3627514:G:A	G162E	0.997
1:3627601:T:C	F191S	0.997
1:3627610:A:G	H194R	0.997
1:3628532:G:A	G250R	0.997
1:3628532:G:C	G250R	0.997
1:3628533:G:A	G250E	0.997
1:3625442:G:C	A74P	0.996
1:3625727:A:T	N103I	0.996
1:3625739:A:T	E107V	0.996
1:3625748:T:A	V110E	0.996
1:3625751:T:C	L111P	0.996

dbSNP variants (sampled 300 via entrez): RS1000532298 (1:3623899 C>G), RS1000762719 (1:3629185 G>A), RS1001342346 (1:3627926 G>A), RS1001880513 (1:3628096 C>A), RS1002069619 (1:3623675 C>T), RS1002100658 (1:3623519 T>C), RS1002747531 (1:3626918 C>T), RS1003069386 (1:3624973 G>A,C,T), RS1003838958 (1:3628080 A>G), RS1004233840 (1:3626975 G>A), RS1004371184 (1:3627178 T>C), RS1004826460 (1:3629671 T>C), RS1005030098 (1:3624770 G>A), RS1005279766 (1:3625599 C>A,G,T), RS1005301267 (1:3626184 G>T)

Disease associations

OMIM: gene MIM:611460 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
Resveratrol	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Coumestrol	affects cotreatment, decreases expression	1
Demecolcine	increases expression	1
Diazinon	increases methylation	1
Diethylstilbestrol	decreases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
Vincristine	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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