PRRG1

Summary

PRRG1 (proline rich and Gla domain 1, HGNC:9469) is a protein-coding gene on chromosome Xp21.1, encoding Transmembrane gamma-carboxyglutamic acid protein 1 (O14668).

This gene encodes a vitamin K-dependent, gamma-carboxyglutamic acid (Gla)-containing, single-pass transmembrane protein. This protein contains a Gla domain at the N-terminus, preceded by a propeptide sequence required for post-translational gamma-carboxylation of specific glutamic acid residues by a vitamin K-dependent gamma-carboxylase. The C-terminus is proline-rich containing PPXY and PXXP motifs found in a variety of signaling and cytoskeletal proteins. This gene is highly expressed in the spinal cord. Several alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5638 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001142395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9469
Approved symbol	PRRG1
Name	proline rich and Gla domain 1
Location	Xp21.1
Locus type	gene with protein product
Status	Approved
Aliases	PRGP1
Ensembl gene	ENSG00000130962
Ensembl biotype	protein_coding
OMIM	300935
Entrez	5638

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000378628, ENST00000449135, ENST00000463135, ENST00000466533, ENST00000470290, ENST00000484460, ENST00000491253, ENST00000850644, ENST00000850645, ENST00000868170, ENST00000868171, ENST00000868172, ENST00000868173, ENST00000868174, ENST00000868175, ENST00000868176, ENST00000868177, ENST00000868178, ENST00000960027, ENST00000960028, ENST00000960029

RefSeq mRNA: 5 — MANE Select: NM_001142395 NM_000950, NM_001142395, NM_001173486, NM_001173489, NM_001173490

CCDS: CCDS14239, CCDS55397

Canonical transcript exons

ENST00000378628 — 4 exons

Exon	Start	End
ENSE00001478146	37349364	37349395
ENSE00001926280	37453136	37457291
ENSE00003481103	37425840	37426000
ENSE00003481684	37406209	37406259

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2715 / max 488.4674, expressed in 1565 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195890	15.8762	1560
195889	1.3952	798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	96.60	gold quality
corpus callosum	UBERON:0002336	96.17	gold quality
middle frontal gyrus	UBERON:0002702	94.85	gold quality
medial globus pallidus	UBERON:0002477	93.70	gold quality
spinal cord	UBERON:0002240	93.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.40	gold quality
medulla oblongata	UBERON:0001896	93.38	gold quality
endothelial cell	CL:0000115	93.07	gold quality
cranial nerve II	UBERON:0000941	92.86	gold quality
globus pallidus	UBERON:0001875	92.75	gold quality
subthalamic nucleus	UBERON:0001906	92.75	gold quality
CA1 field of hippocampus	UBERON:0003881	92.69	gold quality
pons	UBERON:0000988	92.39	gold quality
superior vestibular nucleus	UBERON:0007227	92.16	gold quality
inferior olivary complex	UBERON:0002127	92.11	gold quality
vastus lateralis	UBERON:0001379	91.17	gold quality
choroid plexus epithelium	UBERON:0003911	90.86	gold quality
ventral tegmental area	UBERON:0002691	90.61	gold quality
quadriceps femoris	UBERON:0001377	90.32	gold quality
midbrain	UBERON:0001891	89.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.98	gold quality
substantia nigra	UBERON:0002038	88.97	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.63	gold quality
biceps brachii	UBERON:0001507	88.07	gold quality
skeletal muscle tissue	UBERON:0001134	87.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.80	gold quality
calcaneal tendon	UBERON:0003701	87.43	gold quality
deltoid	UBERON:0001476	87.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

190 targeting PRRG1, 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-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prrg1	ENSDARG00000043283
mus_musculus	Prrg1	ENSMUSG00000047996
rattus_norvegicus	Prrg1	ENSRNOG00000089620

Paralogs (3): PRRG3 (ENSG00000130032), PRRG4 (ENSG00000135378), OVCH2 (ENSG00000183378)

Protein

Protein identifiers

Transmembrane gamma-carboxyglutamic acid protein 1 — O14668 (reviewed: O14668)

Alternative names: Proline-rich gamma-carboxyglutamic acid protein 1

All UniProt accessions (3): O14668, C9J6P5, C9JNY5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Highly expressed in the spinal cord.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O14668-1	1	yes
O14668-2	2

RefSeq proteins (5): NP_000941, NP_001135867, NP_001166957, NP_001166960, NP_001166961 (=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 (12 total): topological domain 2, splice variant 2, propeptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9WFL	ELECTRON MICROSCOPY	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14668-F1	69.20	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 37–42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_WOUND_HEALING, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, CCCNNNNNNAAGWT_UNKNOWN, IVANOVA_HEMATOPOIESIS_STEM_CELL_SHORT_TERM, P300_01, GOBP_HEMOSTASIS, GCM_MAPK10, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, ATGTTTC_MIR494, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, KIM_MYCN_AMPLIFICATION_TARGETS_UP, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, GCM_DLG1

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

GO Molecular Function (3): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576), membrane (GO:0016020)

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
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRRG1	GGCX	P38435	932
PRRG1	UCMA	Q8WVF2	595
PRRG1	LANCL3	Q6ZV70	539
PRRG1	MGP	P08493	479
PRRG1	RFFL	Q8WZ73	432
PRRG1	YAP1	P46937	427
PRRG1	SLC44A1	Q8WWI5	420
PRRG1	CMTM3	Q96MX0	410
PRRG1	DYNLT3	P51808	409
PRRG1	ABHD4	Q8TB40	408
PRRG1	TMEM47	Q9BQJ4	407
PRRG1	MAGEB16	A2A368	403
PRRG1	FAM47B	Q8NA70	393
PRRG1	FA2H	Q7L5A8	387
PRRG1	OR2AE1	Q8NHA4	369

IntAct

7 interactions, top by confidence:

A	B	Type	Score
PRRG1	UQCRH	psi-mi:“MI:0915”(physical association)	0.560
NEDD4	PRRG1	psi-mi:“MI:0914”(association)	0.350
PRRG1	YAP1	psi-mi:“MI:0914”(association)	0.350
PRRG1	GGCX	psi-mi:“MI:0914”(association)	0.350
UQCRH	PRRG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): UQCRH (Two-hybrid), DCAF10 (Affinity Capture-MS), STXBP4 (Affinity Capture-MS), ITCH (Affinity Capture-MS), WWP1 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), YAP1 (Affinity Capture-MS), PRRG1 (Affinity Capture-MS), HECW2 (Affinity Capture-MS), NEDD4L (Affinity Capture-MS), HECW1 (Affinity Capture-MS), GGCX (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), PRRG1 (Proximity Label-MS), PRRG1 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSN8, A0A1B0GSZ0, A0A1B0GVQ0, A0A1B0GVT2, A0A1B0GWG4, A2A2V5, A2A9G7, A2APA5, A2VE22, A6NFZ4, A6QQ93, A7E1Z1, A7MB05, A9CBA0, B7ZWI3, D3ZR35, E9Q942, F5HAK6, F5HFG3, O14668, O39519, O39920, P09312, P0DJ93, P18345, P86045, Q2KIK3, Q498C7, Q5RCB6, Q5RF07, Q5RF75, Q67593, Q68D42, Q6AXS2, Q6UWT2, Q77NN6, Q7M750, Q80WK2, Q8BGN6

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1679 predictions. Top by Δscore:

Variant	Effect	Δscore
X:37349393:GCT:G	donor_gain	1.0000
X:37349396:G:GG	donor_gain	1.0000
X:37349459:G:GT	donor_gain	1.0000
X:37406255:GAGGG:G	donor_gain	1.0000
X:37406257:GGG:G	donor_gain	1.0000
X:37406258:GG:G	donor_gain	1.0000
X:37406258:GGG:G	donor_gain	1.0000
X:37406259:GG:G	donor_gain	1.0000
X:37425838:A:AG	acceptor_gain	1.0000
X:37425839:G:GG	acceptor_gain	1.0000
X:37425996:AAACT:A	donor_gain	1.0000
X:37425997:AACT:A	donor_gain	1.0000
X:37425998:ACT:A	donor_gain	1.0000
X:37425998:ACTG:A	donor_loss	1.0000
X:37425999:CT:C	donor_gain	1.0000
X:37425999:CTGTA:C	donor_loss	1.0000
X:37426000:TGTA:T	donor_loss	1.0000
X:37426001:G:GG	donor_gain	1.0000
X:37426001:GT:G	donor_loss	1.0000
X:37426002:T:A	donor_loss	1.0000
X:37426003:A:AG	donor_loss	1.0000
X:37426003:AAG:A	donor_loss	1.0000
X:37426004:AG:A	donor_loss	1.0000
X:37349395:TG:T	donor_loss	0.9900
X:37349396:G:GA	donor_loss	0.9900
X:37349397:TGAG:T	donor_loss	0.9900
X:37349398:GAGT:G	donor_loss	0.9900
X:37349460:A:T	donor_gain	0.9900
X:37406205:ACAG:A	acceptor_gain	0.9900
X:37406207:AG:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000061244 (X:37445462 T>C), RS1000148804 (X:37406246 A>G), RS1000175688 (X:37444907 C>T), RS1000297137 (X:37455356 C>T), RS1000361008 (X:37398323 G>A), RS1000400309 (X:37454264 C>T), RS1000404529 (X:37388882 C>T), RS1000408888 (X:37434599 G>A,T), RS1000485790 (X:37411775 C>G,T), RS1000539184 (X:37411311 C>A), RS1000641087 (X:37379386 C>T), RS1000686182 (X:37354537 C>T), RS1000812657 (X:37419675 T>C), RS1000821974 (X:37354300 G>A), RS1000826761 (X:37428939 C>A)

Disease associations

OMIM: gene MIM:300935 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	increases expression, affects binding, increases reaction, increases abundance	2
mercuric bromide	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
resorcinol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1

Clinical trials (associated diseases)

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