GPATCH3

Summary

GPATCH3 (G-patch domain containing 3, HGNC:25720) is a protein-coding gene on chromosome 1p36.11, encoding G patch domain-containing protein 3 (Q96I76). Involved in transcriptional regulation.

Predicted to enable nucleic acid binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and positive regulation of DNA-templated transcription. Located in cytosol and nucleoplasm.

Source: NCBI Gene 63906 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital glaucoma (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_022078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25720
Approved symbol	GPATCH3
Name	G-patch domain containing 3
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12455
Ensembl gene	ENSG00000198746
Ensembl biotype	protein_coding
OMIM	617486
Entrez	63906

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000361720, ENST00000445019, ENST00000450844, ENST00000945224

RefSeq mRNA: 1 — MANE Select: NM_022078 NM_022078

CCDS: CCDS290

Canonical transcript exons

ENST00000361720 — 7 exons

Exon	Start	End
ENSE00000956138	26894236	26894410
ENSE00000956139	26893389	26893448
ENSE00000956140	26892670	26892791
ENSE00000956141	26892411	26892538
ENSE00001224291	26890488	26891226
ENSE00001649845	26897301	26897725
ENSE00001866288	26899992	26900467

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 89.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4370 / max 108.3331, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11200	10.2295	1804
11199	0.2075	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.85	gold quality
granulocyte	CL:0000094	87.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.28	gold quality
gastrocnemius	UBERON:0001388	85.12	gold quality
muscle of leg	UBERON:0001383	84.67	gold quality
monocyte	CL:0000576	84.35	gold quality
leukocyte	CL:0000738	84.15	gold quality
mononuclear cell	CL:0000842	84.03	gold quality
lower esophagus mucosa	UBERON:0035834	83.06	gold quality
apex of heart	UBERON:0002098	82.93	gold quality
right adrenal gland cortex	UBERON:0035827	82.88	gold quality
mucosa of transverse colon	UBERON:0004991	82.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.69	gold quality
right adrenal gland	UBERON:0001233	82.25	gold quality
left adrenal gland	UBERON:0001234	81.71	gold quality
skin of leg	UBERON:0001511	81.49	gold quality
left adrenal gland cortex	UBERON:0035825	81.40	gold quality
stromal cell of endometrium	CL:0002255	80.89	gold quality
skin of abdomen	UBERON:0001416	80.88	gold quality
right lobe of liver	UBERON:0001114	80.82	gold quality
body of stomach	UBERON:0001161	80.48	gold quality
prefrontal cortex	UBERON:0000451	80.46	gold quality
ventricular zone	UBERON:0003053	80.45	gold quality
adrenal cortex	UBERON:0001235	80.05	gold quality
adrenal gland	UBERON:0002369	79.70	gold quality
right frontal lobe	UBERON:0002810	79.65	gold quality
lower esophagus	UBERON:0013473	79.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting GPATCH3, 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-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-5195-5P	90.84	65.09	287

Literature-anchored findings (GeneRIF, showing 2)

• The results show the existence of high genetic heterogeneity in congenital glaucoma and the role of GPATCH3 in this disease. GPATCH3 is a new gene involved in ocular and craniofacial development. (PMID:28397860)
• GPATCH3 interacts with VISA and disrupts the assembly of virus-induced VISA signalosome therefore acts as a negative regulator of RLR-mediated innate antiviral immune responses. (PMID:28414768)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpatch3	ENSDARG00000052747
mus_musculus	Gpatch3	ENSMUSG00000028850
rattus_norvegicus	Gpatch3	ENSRNOG00000007097
caenorhabditis_elegans		WBGENE00019467

Protein

Protein identifiers

G patch domain-containing protein 3 — Q96I76 (reviewed: Q96I76)

All UniProt accessions (3): Q96I76, H0Y5H5, Q5JYG5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcriptional regulation. It is able to activate transcription from the CXCR4 promoter and therefore it might control neural crest cell migration involved in ocular and craniofacial development. Is a negative regulator of immune antiviral response, acting via down-regulation of RIG-I-like receptors signaling and inhibition of type I interferon production. The control mechanism involves interaction with mitochondrial MAVS and inhibition of MAVS assembly with downstream proteins implicated in antiviral response, such as TBK1 and TRAF6.

Subunit / interactions. Interacts with mitochondrial MAVS; the interaction is markedly increased upon viral infection.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in ocular tissues including retinal pigment epithelium, cornea, ciliary muscle and non-pigmented ciliary epithelium. Also expressed in optic nerve, cartilage, skin and lymph node.

Disease relevance. GPATCH3 variants may be involved in the pathogenesis of congenital glaucoma, an ocular disease characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.

RefSeq proteins (1): NP_071361* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000467	G_patch_dom	Domain
IPR040341	GPATCH3	Family

Pfam: PF01585

UniProt features (11 total): sequence variant 4, sequence conflict 2, compositionally biased region 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96I76-F1	68.01	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): MODULE_255, MODULE_317, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (3): negative regulation of type I interferon production (GO:0032480), negative regulation of RIG-I signaling pathway (GO:0039536), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
RIG-I signaling pathway	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
regulation of RIG-I signaling pathway	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPATCH3	AMMECR1L	Q6DCA0	571
GPATCH3	CC2D1B	Q5T0F9	570
GPATCH3	RSPRY1	Q96DX4	570
GPATCH3	EAF1	Q96JC9	550
GPATCH3	CLXN	Q9HAE3	532
GPATCH3	ZNRF2	Q8NHG8	488
GPATCH3	TMUB2	Q71RG4	485
GPATCH3	METTL6	Q8TCB7	474
GPATCH3	COG7	P83436	464
GPATCH3	NOL7	Q9UMY1	463
GPATCH3	PRPF38A	Q8NAV1	454
GPATCH3	FKBP14	Q9NWM8	452
GPATCH3	PLEKHA8	Q96JA3	448
GPATCH3	CNOT10	Q9H9A5	446
GPATCH3	SNX20	Q7Z614	444

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GPATCH3	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
GPATCH3	DHX15	psi-mi:“MI:0914”(association)	0.350
	GPATCH3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): GPATCH3 (Proximity Label-MS), DHX15 (Affinity Capture-MS), PAXBP1 (Affinity Capture-MS), GPATCH3 (Affinity Capture-MS), GPATCH3 (Proximity Label-MS), GPATCH3 (Proximity Label-MS), GPATCH3 (Proximity Label-MS), GPATCH3 (Proximity Label-MS)

ESM2 similar proteins: A0A8I6ASZ5, A0JN53, A1L1L2, A4FV45, D3Z8X7, D3ZND0, E1C760, E7EXT2, F1MX48, F7AEX0, O75800, P78316, Q0VBD2, Q1RM35, Q2YD98, Q3SYU1, Q3T1I9, Q3TYL0, Q5PPF5, Q5R8S0, Q61249, Q66HA5, Q80TE0, Q80V31, Q80XC6, Q8BIW9, Q8BM55, Q8BRN9, Q8C2K1, Q8C3S2, Q8K1A6, Q8K2Z4, Q8N163, Q8R3N1, Q8VDM1, Q8VDP4, Q91WR3, Q96I76, Q99PL6, Q9BWH6

Diamond homologs: Q8BIY1, Q96I76

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

999 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26892665:CTCA:C	donor_loss	1.0000
1:26892667:CAC:C	donor_loss	1.0000
1:26892668:A:AC	donor_gain	1.0000
1:26892669:C:CA	donor_loss	1.0000
1:26892669:C:CC	donor_gain	1.0000
1:26892787:ACCAT:A	acceptor_gain	1.0000
1:26892788:CCAT:C	acceptor_gain	1.0000
1:26892788:CCATC:C	acceptor_gain	1.0000
1:26892789:CAT:C	acceptor_gain	1.0000
1:26892789:CATC:C	acceptor_gain	1.0000
1:26892790:AT:A	acceptor_gain	1.0000
1:26892791:TCTG:T	acceptor_loss	1.0000
1:26892792:C:CC	acceptor_gain	1.0000
1:26892792:C:CG	acceptor_loss	1.0000
1:26892793:T:A	acceptor_loss	1.0000
1:26893306:AG:A	donor_gain	1.0000
1:26894230:CATTA:C	donor_loss	1.0000
1:26894232:TTA:T	donor_loss	1.0000
1:26894233:TAC:T	donor_loss	1.0000
1:26894234:ACCT:A	donor_gain	1.0000
1:26894235:CCTC:C	donor_gain	1.0000
1:26894237:T:TA	donor_gain	1.0000
1:26894244:T:TA	donor_gain	1.0000
1:26894247:T:TA	donor_gain	1.0000
1:26894302:A:AC	donor_gain	1.0000
1:26894303:C:CC	donor_gain	1.0000
1:26894312:AATCT:A	donor_gain	1.0000
1:26894316:T:TA	donor_gain	1.0000
1:26894319:T:TA	donor_gain	1.0000
1:26894407:CGTC:C	acceptor_gain	1.0000

AlphaMissense

3387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26894300:C:A	W329C	0.996
1:26894300:C:G	W329C	0.996
1:26900067:A:G	W126R	0.995
1:26900067:A:T	W126R	0.995
1:26894302:A:G	W329R	0.994
1:26894302:A:T	W329R	0.994
1:26900065:C:A	W126C	0.994
1:26900065:C:G	W126C	0.994
1:26894273:A:C	F338L	0.993
1:26894273:A:T	F338L	0.993
1:26894275:A:G	F338L	0.993
1:26900298:A:C	Y49D	0.988
1:26892503:C:A	W423C	0.987
1:26892503:C:G	W423C	0.987
1:26892505:A:G	W423R	0.987
1:26892505:A:T	W423R	0.987
1:26897599:C:A	G193V	0.987
1:26900131:G:C	C104W	0.987
1:26900301:G:C	H48D	0.986
1:26900357:A:G	L29S	0.986
1:26900066:C:G	W126S	0.985
1:26900345:A:G	F33S	0.985
1:26897626:A:G	L184P	0.984
1:26900029:A:C	C138W	0.984
1:26900302:G:C	F47L	0.984
1:26900302:G:T	F47L	0.984
1:26900304:A:G	F47L	0.984
1:26900384:A:G	I20T	0.983
1:26900133:A:G	C104R	0.982
1:26897599:C:T	G193E	0.981

dbSNP variants (sampled 300 via entrez): RS1000217807 (1:26897915 T>C), RS1000321399 (1:26897359 C>G,T), RS1000324343 (1:26898924 C>G), RS1000378599 (1:26898641 C>A), RS1000431171 (1:26891842 G>A), RS1000523785 (1:26890670 T>C), RS1000572318 (1:26891146 T>A,C), RS1000593739 (1:26892034 G>C), RS1000713473 (1:26897150 A>G), RS1001105105 (1:26902238 T>A), RS1001223568 (1:26896540 A>AAAT), RS1001490205 (1:26890244 G>A,C), RS1001716532 (1:26901845 G>A), RS1001858851 (1:26890373 G>A,C,T), RS1002280044 (1:26894807 GT>G)

Disease associations

OMIM: gene MIM:617486 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital glaucoma	Limited	Autosomal recessive

Mondo (1): congenital glaucoma (MONDO:0020366)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007611_16	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	6.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006871	Hydrophthalmos	C11.250.480; C11.525.381.407.480; C16.131.384.480; C16.614.438

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Atrazine	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04947124	PHASE2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT01460017	PHASE1	UNKNOWN	Comparison Between Deep Sclerectomy and Traditional Trabeculotomy & Trabeculectomy in Congenital Glaucoma
NCT02121171	PHASE1	UNKNOWN	Combined Trab+Trab Versus Combined Trab+Trab With Subconjunctival Implantation of Ologen for Primary Congenital Glaucoma
NCT01020721	Not specified	UNKNOWN	The Genetic Characteristics in South Korean Patients With Primary Congenital Glaucoma
NCT01136460	Not specified	UNKNOWN	Genetic Testing in Primary Congenital Glaucoma Patients
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03077789	Not specified	COMPLETED	Prospective Study of the Diagnostic and Therapeutic Management of Congenital Glaucoma in France
NCT03541551	Not specified	COMPLETED	Ologen® Collagen Matrix in Patients With Primary Congenital Glaucoma Undergoing Trabeculectomy
NCT04079725	Not specified	UNKNOWN	Iris Tissue in Primary Congenital Glaucoma
NCT04116450	Not specified	COMPLETED	MicrocatheterTrabeculotomy in Primary Congenital Glaucoma
NCT04381611	Not specified	ENROLLING_BY_INVITATION	INTEGRAL Study: A Longitudinal Study of Surgeries and Lasers in Glaucoma: Long-term Results and Success Predictors Analysed From a Large-scale Retrospective and Prospective Glaucoma Register
NCT04647929	Not specified	WITHDRAWN	Comparison of Surgical Treatment Options for Primary Congenital and Developmental Glaucomas
NCT04683289	Not specified	COMPLETED	Visco-Circumferential-Suture-Trabeculotomy Versus Trabeculotomy
NCT04709497	Not specified	UNKNOWN	Surgery for Primary Congenital Glaucoma in Neonates
NCT04949555	Not specified	UNKNOWN	Long Term Evaluation of Primary Congenital Glaucoma Management in Sohag University Hospital
NCT05011747	Not specified	UNKNOWN	Viscotrabeculotomy in Pediatric Glaucoma Following Cataract Surgery
NCT05115708	Not specified	UNKNOWN	Kahook Dual Blade Ab-interno Trabeculotomy Versus ab Externo Viscotrabeculotomy in Primary Congenital Glaucoma
NCT05205122	Not specified	UNKNOWN	Evaluation of Primary Congenital Glaucoma at Asyut University Hospital
NCT05943184	Not specified	COMPLETED	Cognitive Behavioral Nursing Model
NCT06189326	Not specified	UNKNOWN	Non-penetrating Deep Sclerectomy Versus Trabeculotomy- Trabeculectomy Operation in Treatment of Primary Congenital Glaucoma
NCT07012252	Not specified	COMPLETED	Optical Coherence Tomography of the Irido-Corneal Angle Before and After Goniotomy and Trabeculotomy in Primary Congenital Glaucoma
NCT07504315	Not specified	NOT_YET_RECRUITING	Study Aim to Compare the Effect of Different Technique of Airway Managment During Anaesthesia on the Haemodynamics and Intraocular Pressure. Patients Were Divided Into Three Groups of 25 Patients Each. (Group A); Patients Who Were Subjected to LMA Insertion (Group B ).
NCT07550868	Not specified	NOT_YET_RECRUITING	Goniotomy in Primary Congenital Glaucoma