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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): congenital glaucoma (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• GTEx eGene: eQTL in 3 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_022078
• Notable: 103 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 9 — 5 protein_coding, 4 nonsense_mediated_decay

MANE Select: ENST00000361720

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1

ENST00000361720, ENST00000445019, ENST00000450844, ENST00000945224, ENST00000996817, ENST00000996818, ENST00001046089, ENST00001046090, ENST00001102682

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.

Highest expression (Bgee): primordial germ cell in gonad, granulocyte, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GPATCH3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

3 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.2e-02	+0.44	1:26585890:C:T
Cells Cultured fibroblasts	eqtl	2.3e-02	+0.33	1:26803734:G:C
Whole Blood	eqtl	2.4e-02	+0.33	1:26261856:A:G

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 278 tissues 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
spleen	UBERON:0002106	79.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.12	gold quality
transverse colon	UBERON:0001157	79.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.99	gold quality
islet of Langerhans	UBERON:0000006	78.91	gold quality
esophagus	UBERON:0001043	78.80	gold quality
esophagus mucosa	UBERON:0002469	78.71	gold quality
muscle organ	UBERON:0001630	78.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.60	gold quality
cerebellar hemisphere	UBERON:0002245	78.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.41	gold quality
cerebellar cortex	UBERON:0002129	78.39	gold quality
right lobe of thyroid gland	UBERON:0001119	78.37	gold quality
mucosa of stomach	UBERON:0001199	78.37	gold quality
metanephros cortex	UBERON:0010533	78.30	gold quality
body of uterus	UBERON:0009853	78.29	gold quality
popliteal artery	UBERON:0002250	78.16	gold quality
ganglionic eminence	UBERON:0004023	78.16	gold quality
tibial artery	UBERON:0007610	78.15	gold quality
zone of skin	UBERON:0000014	78.12	gold quality
descending thoracic aorta	UBERON:0002345	78.11	gold quality
stomach	UBERON:0000945	78.05	gold quality
cortical plate	UBERON:0005343	77.89	gold quality
anterior cingulate cortex	UBERON:0009835	77.84	gold quality
cingulate cortex	UBERON:0003027	77.74	gold quality
tibial nerve	UBERON:0001323	77.70	gold quality
upper lobe of left lung	UBERON:0008952	77.70	gold quality
small intestine	UBERON:0002108	77.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.60	gold quality
left coronary artery	UBERON:0001626	77.59	gold quality
aorta	UBERON:0000947	77.53	gold quality
left lobe of thyroid gland	UBERON:0001120	77.51	gold quality
omental fat pad	UBERON:0010414	77.45	gold quality
peritoneum	UBERON:0002358	77.40	gold quality
left uterine tube	UBERON:0001303	77.37	gold quality
minor salivary gland	UBERON:0001830	77.30	gold quality
ectocervix	UBERON:0012249	77.25	gold quality
spinal cord	UBERON:0002240	77.15	gold quality
endocervix	UBERON:0000458	77.14	gold quality
heart left ventricle	UBERON:0002084	77.09	gold quality
thoracic aorta	UBERON:0001515	77.04	gold quality
adenohypophysis	UBERON:0002196	76.91	gold quality
ascending aorta	UBERON:0001496	76.86	gold quality
right ovary	UBERON:0002118	76.85	gold quality
body of pancreas	UBERON:0001150	76.82	gold quality
right testis	UBERON:0004534	76.77	gold quality
cerebellum	UBERON:0002037	76.73	gold quality
left testis	UBERON:0004533	76.73	gold quality
right coronary artery	UBERON:0001625	76.70	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.57	gold quality
pancreas	UBERON:0001264	76.41	gold quality
coronary artery	UBERON:0001621	76.41	gold quality
cardiac ventricle	UBERON:0002082	76.40	gold quality
upper lobe of lung	UBERON:0008948	76.22	gold quality
neocortex	UBERON:0001950	76.16	gold quality
left ovary	UBERON:0002119	76.16	gold quality
blood	UBERON:0000178	76.12	gold quality
ileal mucosa	UBERON:0000331	76.09	gold quality
frontal cortex	UBERON:0001870	76.08	gold quality
thyroid gland	UBERON:0002046	76.04	gold quality
right atrium auricular region	UBERON:0006631	75.95	gold quality
colon	UBERON:0001155	75.92	gold quality
amygdala	UBERON:0001876	75.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.88	gold quality
rectum	UBERON:0001052	75.79	gold quality
pituitary gland	UBERON:0000007	75.76	gold quality
intestine	UBERON:0000160	75.74	gold quality
gall bladder	UBERON:0002110	75.67	gold quality
putamen	UBERON:0001874	75.61	gold quality
lymph node	UBERON:0000029	75.54	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	21.9	high
Skeletal muscle	tissue	13.8	medium
Nucleus accumbens	tissue	13.6
Locus coeruleus	tissue	13.3
Hippocampus	tissue	12.5	not detected
Postcentral gyrus	tissue	12.4
Choroid plexus	tissue	12.1
Tongue	tissue	11.5
Skin 1	tissue	9.2	medium
Thymus	tissue	8.7
Lymph node	tissue	8.4	low
Epididymis	tissue	8.4	not detected
Cerebellum	tissue	8.3	low
Duodenum	tissue	8.0	medium
Corpus callosum	tissue	8.0
Spleen	tissue	7.6	not detected
Parathyroid gland	tissue	7.5	not detected
Placenta	tissue	7.5	medium
Ovary	tissue	7.4	not detected
Pituitary gland	tissue	7.3
Adipose tissue	tissue	7.3	not detected
Pancreas	tissue	7.2	not detected
Vagina	tissue	7.1	medium
Colon	tissue	7.1	low
Spinal cord	tissue	7.1
Tonsil	tissue	7.0	not detected
Small intestine	tissue	6.8	medium
Testis	tissue	6.7	low
Stomach 1	tissue	6.5	low
Endometrium 1	tissue	6.4	not detected
Superior colliculi	tissue	6.3
Substantia nigra	tissue	6.3
Lung	tissue	6.3	low
Adrenal gland	tissue	6.2	medium
Medulla oblongata	tissue	6.1
Heart muscle	tissue	6.0	medium
Smooth muscle	tissue	6.0	medium
Breast	tissue	5.9	medium
Olfactory bulb	tissue	5.9
Fallopian tube	tissue	5.9	medium
Appendix	tissue	5.9	low
Pons	tissue	5.8
Rectum	tissue	5.8	low
Midbrain	tissue	5.8
Thalamus	tissue	5.8
Thyroid gland	tissue	5.8	not detected
Liver	tissue	5.8	medium
Periaqueductal gray	tissue	5.8
Seminal vesicle	tissue	5.7	not detected
Hypothalamus	tissue	5.7
Esophagus	tissue	5.5	medium
Salivary gland	tissue	5.5	low
Septum	tissue	5.5
Hippocampal formation	tissue	5.4
Gallbladder	tissue	5.3	low
Cervix	tissue	5.2	medium
Putamen	tissue	5.2
Kidney	tissue	5.2	not detected
Retina	tissue	5.0
Urinary bladder	tissue	5.0	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Temporal white matter (18.8), Parieto-temporal junction (white matter) (18.5), Globus pallidus, internus (17.3), Parahippocampal cortex (white matter) (17.2), Globus pallidus, externus (17.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GPATCH3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

23 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 6.08e-13, LOEUF 1.01, missense Z 0.67 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000361720 — one region, missense o/e 0.99.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2442492) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
small spleen	1
enlarged lymph nodes	1
microphthalmia	1
abnormal retina morphology	1
abnormal eye morphology	1
hydrometra	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KDF1	protein-coding	126695
GPN2-AS1	ncRNA	139355241
SFN	protein-coding	2810
GPN2	protein-coding	54707
NR0B2	protein-coding	8431
NUDC	protein-coding	10726
ZDHHC18	protein-coding	84243

Protein

Protein identifiers

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

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

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (4): DNA-templated transcription (GO:0006351), 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

17 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
gene expression	1
RNA biosynthetic process	1
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of RIG-I signaling pathway	BP	mutant phenotype
negative regulation of type I interferon production	BP	mutant phenotype
positive regulation of DNA-templated transcription	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 432 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPATCH3	AMMECR1L	Q6DCA0	654
GPATCH3	EDC3	Q96F86	584
GPATCH3	DDX50	Q9BQ39	578
GPATCH3	CC2D1B	Q5T0F9	564
GPATCH3	PRPF38A	Q8NAV1	557
GPATCH3	GUCA1C	O95843	542
GPATCH3	RSPRY1	Q96DX4	537
GPATCH3	MTMR14	Q8NCE2	535
GPATCH3	EAF1	Q96JC9	530
GPATCH3	CNOT10	Q9H9A5	501
GPATCH3	TLK2	Q86UE8	500
GPATCH3	CLXN	Q9HAE3	496
GPATCH3	ZNF346	Q9UL40	494
GPATCH3	ZC3H14	Q6PJT7	478
GPATCH3	COG7	P83436	477

IntAct

Human interaction partners of GPATCH3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
HSPA5	physical association	0.400	1
DHX15	association	0.350	1

BioGRID (7 interactions; top human partners by supporting records): DCAF11 (Proximity Label-MS), DCAF7 (Proximity Label-MS), DHX15 (Affinity Capture-MS), PAXBP1 (Affinity Capture-MS), TOR1AIP2 (Proximity Label-MS), WSB2 (Proximity Label-MS), XPO7 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for GPATCH3: 103 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 555):

Position(s)	Effect	Δscore	Sites
1:26892668–26892669	donor_loss	1.0000	5
1:26892792–26892793	acceptor_loss	1.0000	4
1:26894234–26894235	donor_loss	1.0000	2
1:26894411–26894412	acceptor_loss	1.0000	5
1:26897726–26897727	acceptor_loss	1.0000	4
1:26891227–26891228	acceptor_loss	0.9900	5
1:26894234–26894235	donor_loss	0.9900	3
1:26894238	donor_gain	0.9900
1:26897726–26897727	acceptor_loss	0.9900	2
1:26891227	acceptor_loss	0.9800

AlphaMissense

840 missense substitutions predicted likely pathogenic (of 3,387 scored), across 232 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F33	8	0.933	0.985
F47	8	0.925	0.984
H48	8	0.922	0.986
F338	8	0.920	0.993
N194	8	0.906	0.980
F44	8	0.893	0.975
H51	8	0.881	0.970
F223	8	0.876	0.971
D341	8	0.871	0.933
F202	8	0.869	0.961
D361	8	0.858	0.922
F406	8	0.805	0.968
D376	8	0.788	0.892
W126	7	0.977	0.995
W329	7	0.972	0.996
W423	7	0.966	0.987
E183	7	0.958	0.976
M190	7	0.921	0.979
W360	7	0.899	0.970
C138	7	0.898	0.984

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.08e-05
Glioblastoma Multiforme (validation)	favorable	0.000146
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000163
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000699

Disease associations

OMIM: gene MIM:617486 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital glaucoma	Limited	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	amber

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

GWAS associations

1 associations:

Study	Trait	p-value
GCST007611_2	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	6e-12

MeSH disease descriptors

1 disease descriptors:

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 (CPIC guideline: no)

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)

Via MONDO — disease-level, not drug-specific.

25 trials:

NCT	Phase	Status	Title
NCT04947124	Phase 2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT01460017	Phase 1	UNKNOWN	Comparison Between Deep Sclerectomy and Traditional Trabeculotomy & Trabeculectomy in Congenital Glaucoma
NCT02121171	Phase 1	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
NCT07701278	Not specified	COMPLETED	Subscleral Trabeculectomy With Inverted T-Shaped Deep Sclerectomy for Primary Congenital Glaucoma
NCT07830017	Not specified	COMPLETED	Combined Nasal Goniotomy-Temporal Trabeculotomy Versus Temporal Trabeculotomy for Management of Primary Congenital Glaucoma