LARGE2

Summary

LARGE2 (LARGE xylosyl- and glucuronyltransferase 2, HGNC:16522) is a protein-coding gene on chromosome 11p11.2, encoding Xylosyl- and glucuronyltransferase LARGE2 (Q8N3Y3). Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with….

Predicted to enable dystroglycan binding activity; glucuronosyltransferase activity; and xylosyltransferase activity. Involved in protein O-linked mannosylation. Predicted to be located in intracellular membrane-bounded organelle. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 120071 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• MANE Select transcript: NM_001300721

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16522
Approved symbol	LARGE2
Name	LARGE xylosyl- and glucuronyltransferase 2
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	PP5656, FLJ35207
Ensembl gene	ENSG00000165905
Ensembl biotype	protein_coding
OMIM	609709
Entrez	120071

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 25 protein_coding, 4 retained_intron

ENST00000325468, ENST00000401752, ENST00000414027, ENST00000525609, ENST00000528236, ENST00000529052, ENST00000530437, ENST00000531526, ENST00000531847, ENST00000534410, ENST00000861589, ENST00000861590, ENST00000861591, ENST00000861592, ENST00000861593, ENST00000926368, ENST00000926369, ENST00000926370, ENST00000926371, ENST00000926372, ENST00000926373, ENST00000926374, ENST00000926375, ENST00000926376, ENST00000926377, ENST00000926378, ENST00000926379, ENST00000926380, ENST00000926381

RefSeq mRNA: 3 — MANE Select: NM_001300721 NM_001300721, NM_001300722, NM_152312

CCDS: CCDS31473, CCDS76399

Canonical transcript exons

ENST00000401752 — 14 exons

Exon	Start	End
ENSE00001548140	45922656	45922728
ENSE00003469077	45926222	45926347
ENSE00003503597	45926442	45926597
ENSE00003511481	45926711	45926871
ENSE00003533942	45922821	45923167
ENSE00003547214	45926039	45926151
ENSE00003577162	45924785	45924889
ENSE00003609977	45923473	45923555
ENSE00003622885	45924154	45924277
ENSE00003638645	45928630	45929096
ENSE00003670375	45928177	45928372
ENSE00003670751	45924506	45924677
ENSE00003677902	45927315	45927593
ENSE00003682007	45927920	45928069

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 92.13.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4629 / max 206.8410, expressed in 528 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114062	3.4339	524
114061	0.0289	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.40	gold quality
metanephros cortex	UBERON:0010533	89.15	gold quality
body of pancreas	UBERON:0001150	89.09	gold quality
skin of abdomen	UBERON:0001416	88.70	gold quality
right lobe of thyroid gland	UBERON:0001119	88.55	gold quality
esophagus mucosa	UBERON:0002469	87.75	gold quality
left lobe of thyroid gland	UBERON:0001120	87.61	gold quality
minor salivary gland	UBERON:0001830	87.26	gold quality
skin of leg	UBERON:0001511	86.87	gold quality
placenta	UBERON:0001987	86.78	gold quality
thyroid gland	UBERON:0002046	86.78	gold quality
saliva-secreting gland	UBERON:0001044	86.11	gold quality
adenohypophysis	UBERON:0002196	86.02	gold quality
pituitary gland	UBERON:0000007	85.93	gold quality
mouth mucosa	UBERON:0003729	85.84	gold quality
zone of skin	UBERON:0000014	85.50	gold quality
pancreas	UBERON:0001264	84.35	gold quality
upper arm skin	UBERON:0004263	84.32	silver quality
adult mammalian kidney	UBERON:0000082	84.20	gold quality
cortex of kidney	UBERON:0001225	83.37	gold quality
metanephros	UBERON:0000081	82.24	gold quality
granulocyte	CL:0000094	81.89	gold quality
right uterine tube	UBERON:0001302	81.31	gold quality
kidney epithelium	UBERON:0004819	81.26	gold quality
kidney	UBERON:0002113	80.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.41	gold quality
prostate gland	UBERON:0002367	80.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	116.69
E-MTAB-9388	yes	10.87
E-ANND-3	yes	4.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting LARGE2, 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-5692A	100.00	74.40	6850
HSA-MIR-497-5P	99.92	71.83	2674
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-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-346	97.01	66.97	662
HSA-MIR-769-5P	94.45	64.56	603

Literature-anchored findings (GeneRIF, showing 5)

• LARGE2 was found to support the maturation of alpha-dystroglycan more effectively than LARGE. (PMID:15752776)
• Loss of LARGE2 disrupts functional glycosylation of alpha-dystroglycan in prostate cancer (PMID:23223448)
• LARGE2 is negatively regulated by Snail and/or ZEB1, revealing a mechanistic basis for alphaDG hypoglycosylation during prostate cancer progression and metastasis. (PMID:25455932)
• Reduced levels of GYLTL1B and ISPD mRNA associated with increased patient mortality and are the likely cause of alphaDG hypoglycosylation in ccRCC. (PMID:26220087)
• Wnt-driven LARGE2 mediates laminin-adhesive O-glycosylation in human colonic epithelial cells and colorectal cancer. (PMID:32586342)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	large2	ENSDARG00000017058
mus_musculus	Large2	ENSMUSG00000040434
rattus_norvegicus	Large2	ENSRNOG00000006353
drosophila_melanogaster	CG11149	FBGN0031732
drosophila_melanogaster	CG9171	FBGN0031738
drosophila_melanogaster	CG15483	FBGN0032457
drosophila_melanogaster	shams	FBGN0039273
caenorhabditis_elegans	bgnt-1.8	WBGENE00008290
caenorhabditis_elegans		WBGENE00009032
caenorhabditis_elegans	bgnt-1.6	WBGENE00010167
caenorhabditis_elegans		WBGENE00010694
caenorhabditis_elegans		WBGENE00010716
caenorhabditis_elegans	bgnt-1.7	WBGENE00011779
caenorhabditis_elegans		WBGENE00015982
caenorhabditis_elegans		WBGENE00017723

Paralogs (5): LARGE1 (ENSG00000133424), GXYLT1 (ENSG00000151233), GXYLT2 (ENSG00000172986), XXYLT1 (ENSG00000173950), B4GAT1 (ENSG00000174684)

Protein

Protein identifiers

Xylosyl- and glucuronyltransferase LARGE2 — Q8N3Y3 (reviewed: Q8N3Y3)

Alternative names: Glycosyltransferase-like 1B, LARGE xylosyl- and glucuronyltransferase 2

All UniProt accessions (4): E9PIZ2, Q8N3Y3, H0YDB8, H0YDU6

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity and in a phosphorylated-O-mannosyl trisaccharide dependent manner. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Supports the maturation of DAG1 more effectively than LARGE1. In addition, can modify both heparan sulfate (HS)- and chondroitin/dermatan sulfate (CS/DS)-proteoglycans (PGs), namely GPC4, with a glycosaminoglycan (GAG)-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding.

Subunit / interactions. Interacts with B4GAT1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed. Expressed at high level in placenta, pancreas and kidney compared to LARGE. Not expressed in brain.

Cofactor. Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).

Pathway. Protein modification; protein glycosylation.

Similarity. In the C-terminal section; belongs to the glycosyltransferase 49 family. In the N-terminal section; belongs to the glycosyltransferase 8 family.

RefSeq proteins (3): NP_001287650, NP_001287651, NP_689525 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002495	Glyco_trans_8	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR051292	Xyl/GlcA_transferase	Family

Pfam: PF01501, PF13896

Catalyzed reactions (Rhea), 3 shown:

• 3-O-[beta-D-GlcA-(1->3)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP + H(+) (RHEA:57336)
• 3-O-{(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-glucuronate = 3-O-{beta-D-GlcA-(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP + H(+) (RHEA:67924)
• 3-O-{beta-D-GlcA-(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-xylose = 3-O-{(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP + H(+) (RHEA:68368)

UniProt features (20 total): binding site 4, glycosylation site 3, sequence variant 3, sequence conflict 3, region of interest 3, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3Y3-F1	88.11	0.77

Functional residue map

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

Ligand- & substrate-binding residues (4): 523; 201; 203; 521

Glycosylation sites (3): 80, 107, 231

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9939291	Matriglycan biosynthesis on DAG1
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via mannose (GO:0035269), muscle cell cellular homeostasis (GO:0046716), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (9): glucuronosyltransferase activity (GO:0015020), manganese ion binding (GO:0030145), UDP-xylosyltransferase activity (GO:0035252), xylosyltransferase activity (GO:0042285), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
DAG1 glycosylations	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
UDP-glycosyltransferase activity	2
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
cellular homeostasis	1
hexosyltransferase activity	1
transition metal ion binding	1
xylosyltransferase activity	1
pentosyltransferase activity	1
molecular_function	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LARGE2	DAG1	Q14118	913
LARGE2	FKTN	O75072	762
LARGE2	POMT1	Q9Y6A1	746
LARGE2	POMT2	Q9UKY4	742
LARGE2	POMGNT1	Q8WZA1	739
LARGE2	FKRP	Q9H9S5	735
LARGE2	RXYLT1	Q9Y2B1	690
LARGE2	POMK	Q9H5K3	654
LARGE2	B3GALNT2	Q8NCR0	650
LARGE2	POMGNT2	Q8NAT1	626
LARGE2	AGRN	O00468	535
LARGE2	NUDT22	Q9BRQ3	528
LARGE2	DPM2	O94777	526
LARGE2	CRPPA	A4D126	521
LARGE2	TMED6	Q8WW62	500

IntAct

58 interactions, top by confidence:

A	B	Type	Score
B4GAT1	LARGE2	psi-mi:“MI:0915”(physical association)	0.560
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
FRMD3	FAM234B	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
NRG1	HS6ST1	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
IFNE	NAGLU	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
TMEM25	FUZ	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.350
LRRN2	TRIM13	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: O95461, Q21389, Q32NJ7, Q54PG8, Q54SH2, Q5XPT3, Q66PG1, Q66PG2, Q66PG3, Q66PG4, Q6P7A1, Q6PA90, Q8N3Y3, Q9Z1M7, Q555X4, Q5EA01, Q55FD5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of carbohydrates and carbohydrate derivatives	5	12.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1917917	NM_001352027.3(PHF21A):c.1959del (p.Ala654fs)	Pathogenic

SpliceAI

2499 predictions. Top by Δscore:

Variant	Effect	Δscore
11:45921765:A:T	donor_gain	1.0000
11:45921768:G:GT	donor_gain	1.0000
11:45924502:A:AG	acceptor_gain	1.0000
11:45924503:C:G	acceptor_gain	1.0000
11:45924504:A:AG	acceptor_gain	1.0000
11:45924505:G:GG	acceptor_gain	1.0000
11:45924505:GCC:G	acceptor_gain	1.0000
11:45924505:GCCCC:G	acceptor_gain	1.0000
11:45924620:G:GT	donor_gain	1.0000
11:45924675:CTG:C	donor_loss	1.0000
11:45924676:TGGT:T	donor_loss	1.0000
11:45924678:G:GC	donor_loss	1.0000
11:45924679:T:G	donor_loss	1.0000
11:45926221:GGAC:G	acceptor_gain	1.0000
11:45926346:AGGTG:A	donor_loss	1.0000
11:45926347:GGT:G	donor_loss	1.0000
11:45926348:G:GG	donor_gain	1.0000
11:45926348:GT:G	donor_loss	1.0000
11:45926432:T:TA	acceptor_gain	1.0000
11:45926433:G:A	acceptor_gain	1.0000
11:45926594:GCAG:G	donor_gain	1.0000
11:45926595:CAGG:C	donor_loss	1.0000
11:45926598:G:C	donor_loss	1.0000
11:45926598:G:GG	donor_gain	1.0000
11:45926709:A:AG	acceptor_gain	1.0000
11:45926710:G:GG	acceptor_gain	1.0000
11:45927313:A:AG	acceptor_gain	1.0000
11:45927314:G:GG	acceptor_gain	1.0000
11:45927589:CTCAG:C	donor_loss	1.0000
11:45927591:CAG:C	donor_loss	1.0000

AlphaMissense

4649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:45924813:C:A	N231K	0.999
11:45924813:C:G	N231K	0.999
11:45924885:C:A	N255K	0.999
11:45924885:C:G	N255K	0.999
11:45926448:C:G	H339D	0.999
11:45926456:C:A	N341K	0.999
11:45926456:C:G	N341K	0.999
11:45924615:A:T	D201V	0.998
11:45924859:T:A	W247R	0.998
11:45924859:T:C	W247R	0.998
11:45924861:G:C	W247C	0.998
11:45924861:G:T	W247C	0.998
11:45926151:G:C	Q294H	0.998
11:45926151:G:T	Q294H	0.998
11:45926222:G:C	D295H	0.998
11:45926233:C:A	N298K	0.998
11:45926233:C:G	N298K	0.998
11:45926287:T:A	N316K	0.998
11:45926287:T:G	N316K	0.998
11:45924803:T:C	L228P	0.997
11:45924812:A:T	N231I	0.997
11:45924826:T:C	Y236H	0.997
11:45924827:A:G	Y236C	0.997
11:45924878:G:A	G253E	0.997
11:45926223:A:C	D295A	0.997
11:45926223:A:T	D295V	0.997
11:45924803:T:A	L228H	0.996
11:45924811:A:G	N231D	0.996
11:45924817:A:C	S233R	0.996
11:45924819:T:A	S233R	0.996

dbSNP variants (sampled 300 via entrez): RS1000105779 (11:45923367 T>A,G), RS1000128547 (11:45924993 T>C), RS1000172038 (11:45929179 G>A), RS1000203049 (11:45928975 G>A), RS1000479344 (11:45923747 G>C), RS1000566462 (11:45920406 C>T), RS1002267657 (11:45928812 C>A,G), RS1002414381 (11:45925076 G>A), RS1002854210 (11:45924731 G>A), RS1003196868 (11:45920767 C>G,T), RS1003229850 (11:45920505 C>T), RS1003352465 (11:45922007 G>A), RS1003545135 (11:45921088 A>G), RS1003906136 (11:45922383 A>G), RS1003946628 (11:45923000 G>A,C,T)

Disease associations

OMIM: gene MIM:609709 | disease phenotypes: MIM:618725

GenCC curated gene-disease

Mondo (1): intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (MONDO:0032883)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002115_15	Axial length	2.000000e-06
GCST010002_237	Refractive error	1.000000e-10
GCST90026416_4	Mild age-related type 2 diabetes	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	3
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	increases methylation	1
Progesterone	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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