PRRG3

Summary

PRRG3 (proline rich and Gla domain 3, HGNC:30798) is a protein-coding gene on chromosome Xq28, encoding Transmembrane gamma-carboxyglutamic acid protein 3 (Q9BZD7).

This gene encodes a protein which contains a vitamin K-dependent carboxylation/gamma-carboxyglutamic domain. The encoded protein is a member of a family of vitamin K-dependent transmembrane proteins which contain a glutamate-rich extracellular domain.

Source: NCBI Gene 79057 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001372163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30798
Approved symbol	PRRG3
Name	proline rich and Gla domain 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	TMG3
Ensembl gene	ENSG00000130032
Ensembl biotype	protein_coding
OMIM	300685
Entrez	79057

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000370353, ENST00000370354, ENST00000448324, ENST00000448726, ENST00000538575, ENST00000652529, ENST00000674374, ENST00000674441, ENST00000674457, ENST00000884468, ENST00000913985

RefSeq mRNA: 3 — MANE Select: NM_001372163 NM_001372163, NM_001372165, NM_024082

CCDS: CCDS14699, CCDS94688

Canonical transcript exons

ENST00000674457 — 4 exons

Exon	Start	End
ENSE00001310099	151699996	151700156
ENSE00001452450	151700506	151705924
ENSE00001452454	151698784	151698821
ENSE00003898222	151695458	151695544

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 97.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1202 / max 8.4983, expressed in 55 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209865	0.1202	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.31	gold quality
trigeminal ganglion	UBERON:0001675	83.69	gold quality
prefrontal cortex	UBERON:0000451	81.53	gold quality
tibial nerve	UBERON:0001323	81.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.62	gold quality
superior frontal gyrus	UBERON:0002661	80.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.26	gold quality
cortical plate	UBERON:0005343	80.04	gold quality
frontal cortex	UBERON:0001870	79.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.77	gold quality
hypothalamus	UBERON:0001898	79.72	gold quality
neocortex	UBERON:0001950	79.58	gold quality
anterior cingulate cortex	UBERON:0009835	79.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.75	gold quality
ganglionic eminence	UBERON:0004023	78.73	gold quality
right frontal lobe	UBERON:0002810	78.71	gold quality
dorsal root ganglion	UBERON:0000044	78.48	gold quality
primary visual cortex	UBERON:0002436	78.35	gold quality
nucleus accumbens	UBERON:0001882	78.30	gold quality
cerebral cortex	UBERON:0000956	78.26	gold quality
middle temporal gyrus	UBERON:0002771	78.05	gold quality
entorhinal cortex	UBERON:0002728	77.81	gold quality
postcentral gyrus	UBERON:0002581	76.41	gold quality
temporal lobe	UBERON:0001871	75.13	gold quality
parietal lobe	UBERON:0001872	74.84	gold quality
forebrain	UBERON:0001890	74.82	gold quality
occipital lobe	UBERON:0002021	74.45	gold quality
skin of hip	UBERON:0001554	74.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	74.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.36
E-MTAB-6678	no	2.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting PRRG3, 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-12118	100.00	65.88	1270
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3936	97.64	64.47	732

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	PRRG3	ENSDARG00000079102
mus_musculus	Prrg3	ENSMUSG00000033361
rattus_norvegicus	Prrg3	ENSRNOG00000066176

Paralogs (3): PRRG1 (ENSG00000130962), PRRG4 (ENSG00000135378), OVCH2 (ENSG00000183378)

Protein

Protein identifiers

Transmembrane gamma-carboxyglutamic acid protein 3 — Q9BZD7 (reviewed: Q9BZD7)

Alternative names: Proline-rich gamma-carboxyglutamic acid protein 3

All UniProt accessions (6): Q9BZD7, A0A494BZY9, A0A6I8PL69, A6NDZ7, C9J7E6, H7C0C2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Expressed in brain, lung, kidney and heart.

Post-translational modifications. Gla residues are produced after subsequent post-translational modifications of glutamate by a vitamin K-dependent gamma-carboxylase.

RefSeq proteins (3): NP_001359092, NP_001359094, NP_076987 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000294	GLA_domain	Domain
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00594

UniProt features (25 total): modified residue 13, topological domain 2, region of interest 2, propeptide 1, chain 1, disulfide bond 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZD7-F1	64.48	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 (13): 25, 26, 33, 35, 38, 39, 44, 45, 48, 51, 54, 58, 22

Disulfide bonds (1): 36–41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_WOUND_HEALING, RYTTCCTG_ETS2_B, GOBP_HEMOSTASIS, MODULE_48, MODULE_95, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, chrXq28, PILON_KLF1_TARGETS_UP, MODULE_163, P53_DN.V2_UP, LMTK3_TARGET_GENES

GO Biological Process (2): proteolysis (GO:0006508), blood coagulation (GO:0007596)

GO Molecular Function (2): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), membrane (GO:0016020), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1

Protein interactions and networks

STRING

246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRRG3	UCMA	Q8WVF2	571
PRRG3	SSX3	Q99909	541
PRRG3	GGCX	P38435	528
PRRG3	CCDC116	Q8IYX3	469
PRRG3	AGFG2	O95081	447
PRRG3	RFX7	Q2KHR2	432
PRRG3	ZNF3	P13683	419
PRRG3	MGP	P08493	418
PRRG3	LRRC52	Q8N7C0	406
PRRG3	KANK3	Q6NY19	405
PRRG3	RNASE10	Q5GAN6	398
PRRG3	TCF23	Q7RTU1	360
PRRG3	VMAC	Q2NL98	360
PRRG3	CLIC5	Q9NZA1	354
PRRG3	TGM3	Q08188	350

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PRRG3	NEDD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): NEDD4L (Affinity Capture-MS), RNF149 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NEDD4L (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), NEDD4L (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS)

ESM2 similar proteins: A2AR95, A4GWX9, A4IHY6, B9F4Q9, D2KUZ7, D3Z1Q2, O15165, O35181, P0C1G7, P0C6T3, P56975, Q0VA20, Q0VBF2, Q0VFM5, Q3B7T3, Q3UH99, Q3V0I2, Q4KL18, Q4KMG9, Q58DS4, Q5FWP4, Q5R8E0, Q5XG16, Q68FU0, Q6A098, Q6K0P5, Q6PAQ9, Q6UXU6, Q6ZSJ9, Q86YD5, Q8AVJ1, Q8BGE4, Q8BGW2, Q8BWJ4, Q8TB68, Q8WUU8, Q8WVE6, Q90VY2, Q92537, Q93YV5

Diamond homologs: A6MFK7, A6MFK8, A7Z070, B5G6G5, O14668, O14669, O19045, O88947, P00734, P00735, P00740, P00741, P00742, P00743, P00744, P00745, P04070, P07224, P07225, P08709, P16293, P16294, P16296, P18292, P19221, P19540, P22457, P22891, P25155, P31394, P33587, P53813, P70375, P81428, P82807, P83370, P98118, P98139, Q08761, Q14393

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

999 predictions. Top by Δscore:

Variant	Effect	Δscore
X:151698782:A:AG	acceptor_gain	1.0000
X:151698783:G:GG	acceptor_gain	1.0000
X:151698783:GAGAA:G	acceptor_gain	1.0000
X:151700114:C:G	donor_gain	1.0000
X:151700121:G:GT	donor_gain	1.0000
X:151700130:G:GT	donor_gain	1.0000
X:151700130:G:T	donor_gain	1.0000
X:151700131:A:T	donor_gain	1.0000
X:151700503:CAGAT:C	acceptor_loss	1.0000
X:151700504:A:AG	acceptor_gain	1.0000
X:151700504:AG:A	acceptor_loss	1.0000
X:151700505:G:GA	acceptor_gain	1.0000
X:151698777:A:AG	acceptor_gain	0.9900
X:151698781:CA:C	acceptor_loss	0.9900
X:151698782:A:AT	acceptor_loss	0.9900
X:151698783:G:GC	acceptor_loss	0.9900
X:151698783:GA:G	acceptor_gain	0.9900
X:151698783:GAGA:G	acceptor_gain	0.9900
X:151698821:GGTG:G	donor_loss	0.9900
X:151698822:G:T	donor_loss	0.9900
X:151698822:GTGA:G	acceptor_loss	0.9900
X:151698823:T:A	donor_loss	0.9900
X:151699994:A:AG	acceptor_gain	0.9900
X:151699995:G:GG	acceptor_gain	0.9900
X:151699995:GT:G	acceptor_gain	0.9900
X:151700184:G:GT	donor_gain	0.9900
X:151700504:AGAT:A	acceptor_gain	0.9900
X:151700504:AGATG:A	acceptor_gain	0.9900
X:151700505:GA:G	acceptor_gain	0.9900
X:151700505:GAT:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000043866 (X:151694804 G>A), RS1000197478 (X:151698163 T>C), RS1000420762 (X:151704482 G>C), RS1000448446 (X:151695786 C>G), RS1000526477 (X:151699765 T>C), RS1000575145 (X:151706381 G>A), RS1001159363 (X:151697695 C>T), RS1001771979 (X:151699045 C>G,T), RS1001966257 (X:151698338 T>G), RS1002758865 (X:151698698 G>A), RS1002965100 (X:151702377 A>G), RS1003160062 (X:151693453 A>T), RS1003318860 (X:151693263 T>C), RS1003854454 (X:151702894 C>A,T), RS1004002310 (X:151694042 G>A,C)

Disease associations

OMIM: gene MIM:300685 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment	4
bisphenol F	decreases expression, affects cotreatment	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	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
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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