GCNT2

Summary

GCNT2 (glucosaminyl (N-acetyl) transferase 2 (I blood group), HGNC:4204) is a protein-coding gene on chromosome 6p24.3-p24.2, encoding N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase (Q8N0V5). Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans.

This gene encodes the enzyme responsible for formation of the blood group I antigen. The i and I antigens are distinguished by linear and branched poly-N-acetyllactosaminoglycans, respectively. The encoded protein is the I-branching enzyme, a beta-1,6-N-acetylglucosaminyltransferase responsible for the conversion of fetal i antigen to adult I antigen in erythrocytes during embryonic development. Mutations in this gene have been associated with adult i blood group phenotype. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 2651 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 13 with adult I phenotype (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 215 total — 21 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_145649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4204
Approved symbol	GCNT2
Name	glucosaminyl (N-acetyl) transferase 2 (I blood group)
Location	6p24.3-p24.2
Locus type	gene with protein product
Status	Approved
Aliases	IGNT, NAGCT1, bA421M1.1, bA360O19.2, ULG3
Ensembl gene	ENSG00000111846
Ensembl biotype	protein_coding
OMIM	600429
Entrez	2651

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 10 protein_coding, 8 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000265012, ENST00000316170, ENST00000379597, ENST00000397423, ENST00000410107, ENST00000459872, ENST00000461400, ENST00000474518, ENST00000474983, ENST00000475577, ENST00000483204, ENST00000485764, ENST00000488742, ENST00000489225, ENST00000489819, ENST00000495262, ENST00000910531, ENST00000910532, ENST00000942490, ENST00000942491, ENST00000942492

RefSeq mRNA: 4 — MANE Select: NM_145649 NM_001374747, NM_001491, NM_145649, NM_145655

CCDS: CCDS34338, CCDS4512, CCDS4513

Canonical transcript exons

ENST00000495262 — 5 exons

Exon	Start	End
ENSE00001576718	10528631	10529836
ENSE00001578377	10527474	10527660
ENSE00003471594	10621351	10621443
ENSE00003901161	10626417	10629368
ENSE00003902460	10521351	10521417

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 85.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2563 / max 172.5324, expressed in 1040 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65749	1.1884	424
65755	0.9455	418
65752	0.8341	315
65770	0.7345	153
65754	0.6158	293
65751	0.5576	318
65763	0.4616	219
65760	0.3776	75
65756	0.2832	138
65758	0.2255	96

Top tissues by expression

136 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	85.05	gold quality
heart left ventricle	UBERON:0002084	84.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.73	gold quality
apex of heart	UBERON:0002098	84.27	gold quality
duodenum	UBERON:0002114	82.52	gold quality
mucosa of transverse colon	UBERON:0004991	82.45	gold quality
prostate gland	UBERON:0002367	81.92	gold quality
stomach	UBERON:0000945	81.91	gold quality
adult mammalian kidney	UBERON:0000082	81.65	gold quality
body of stomach	UBERON:0001161	81.54	gold quality
kidney	UBERON:0002113	81.32	gold quality
monocyte	CL:0000576	80.52	gold quality
leukocyte	CL:0000738	80.04	gold quality
endometrium	UBERON:0001295	79.88	gold quality
tonsil	UBERON:0002372	79.83	gold quality
liver	UBERON:0002107	79.42	gold quality
ganglionic eminence	UBERON:0004023	79.33	gold quality
bone marrow cell	CL:0002092	78.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.52	gold quality
lung	UBERON:0002048	78.50	gold quality
fundus of stomach	UBERON:0001160	78.21	gold quality
bone marrow	UBERON:0002371	78.20	gold quality
heart	UBERON:0000948	77.32	gold quality
ventricular zone	UBERON:0003053	77.28	gold quality
right lung	UBERON:0002167	77.05	gold quality
right lobe of liver	UBERON:0001114	76.98	gold quality
cortex of kidney	UBERON:0001225	76.83	gold quality
minor salivary gland	UBERON:0001830	76.83	gold quality
upper lobe of left lung	UBERON:0008952	76.68	gold quality
saliva-secreting gland	UBERON:0001044	76.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	39.54
E-ANND-3	no	2.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting GCNT2, 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-3120-5P	100.00	65.56	965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
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-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-9902	99.89	69.15	2250

Literature-anchored findings (GeneRIF, showing 13)

• The I carbohydrate antigen interacts simultaneously with the entire hydrophobic patch in framework region 1 and with the outside surface of Ig heavy chain complementarity-determining region 3, leaving most of the site available for binding other antigens. (PMID:12244172)
• A nonsense mutation in the GCNT2 gene isoforms is associated with autosomal recessive congenital cataract in four distantly related Arab families from Israel. (PMID:15161861)
• role of C/EBPalpha in the induction of the IGnTC gene as well as in I antigen expression (PMID:17855628)
• In the family with the “ii” blood group a novel GCNT2 mutation was found in the cataract patients. (PMID:21541272)
• Results show involvement of GCNT2 in EMT and TGF-beta signaling, and further glycosylation modification of E-cadherin by GCNT2, are the underlying integrative mechanisms for breast cancer metastasis. (PMID:21750175)
• An Alu repeat-mediated genomic GCNT2 deletion underlies congenital cataracts and adult i blood group (PMID:21761136)
• Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of colorectal cancer in the tumor and normal tissues. (PMID:25750292)
• GCNT2 expression is closely associated with invasive potential of prostate cancer. (PMID:26678556)
• This study reports a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family. (PMID:27936067)
• miR-199a/b-5p regulates GCNT2 and I antigen expression in colon cancer cells undergoing EMT (PMID:28542779)
• study suggested that GCNT2 was highly expressed in patients with esophageal squamous cell carcinoma and predicted adverse outcome; overexpression of GCNT2 induces epithelial-mesenchymal transition and promotes migration and invasion in ESCC cells; therefore, GCNT2 may act as a candidate prognostic indicator of outcome and a novel target in ESCC patients (PMID:30575058)
• I-branched glycans catalyzed principally by the I-branching enzyme GCNT2 are now indicated in several malignancies. (PMID:31213534)
• Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target. (PMID:33660254)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Gcnt2	ENSRNOG00000023778
drosophila_melanogaster	oxt	FBGN0015360
drosophila_melanogaster	CG9164	FBGN0030634
caenorhabditis_elegans	gly-15	WBGENE00001640
caenorhabditis_elegans	gly-16	WBGENE00001641
caenorhabditis_elegans	gly-17	WBGENE00001642
caenorhabditis_elegans	gly-18	WBGENE00001643
caenorhabditis_elegans	gly-19	WBGENE00001644
caenorhabditis_elegans		WBGENE00005024
caenorhabditis_elegans		WBGENE00009148
caenorhabditis_elegans	F30A10.4	WBGENE00009263
caenorhabditis_elegans		WBGENE00011090
caenorhabditis_elegans	T09E11.6	WBGENE00011655
caenorhabditis_elegans	T09E11.9	WBGENE00011658
caenorhabditis_elegans	T27F6.1	WBGENE00012102
caenorhabditis_elegans		WBGENE00012135
caenorhabditis_elegans		WBGENE00013119
caenorhabditis_elegans	ZK1225.2	WBGENE00014236
caenorhabditis_elegans		WBGENE00019270
caenorhabditis_elegans		WBGENE00019919

Paralogs (8): XYLT2 (ENSG00000015532), WSCD2 (ENSG00000075035), XYLT1 (ENSG00000103489), GCNT7 (ENSG00000124091), GCNT3 (ENSG00000140297), GCNT4 (ENSG00000176928), WSCD1 (ENSG00000179314), GCNT1 (ENSG00000187210)

Protein

Protein identifiers

N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase — Q8N0V5 (reviewed: Q8N0V5)

Alternative names: I-branching enzyme, IGNT

All UniProt accessions (2): Q8N0V5, B7ZBL3

UniProt curated annotations — full annotation on UniProt →

Function. Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans. Introduces the blood group I antigen during embryonic development. It is closely associated with the development and maturation of erythroid cells. Determines the expression of the blood group I antigen in erythrocytes.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed in lens epithelium cells. Expressed in reticulocytes.

Disease relevance. Cataract 13, with adult i phenotype (CTRCT13) [MIM:116700] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT13 is associated with the rare adult i phenotype, in which adult red blood cells are rich in i antigen and contain low levels of I antigen. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Polymorphism. GCNT2 is involved in determining the blood group I system (Ii) [MIM:110800]. The i (fetal) and I (adult) antigens are determined by linear and branched poly-N-acetyllactosaminoglycans, respectively. A replacement during development of i by I is dependent on the appearance of a beta-1,6-N-acetylglucosaminyltransferase, the I-branching enzyme. The expression of the blood group I antigen in erythrocytes is determined by isoform C of GCNT2.

Similarity. Belongs to the glycosyltransferase 14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N0V5-1	A, IGnTA, IGNT1	yes
Q8N0V5-2	B, IGnTB, IGNT2
Q8N0V5-3	C, IGnTC, IGNT3

RefSeq proteins (4): NP_001361676, NP_001482, NP_663624, NP_663630 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003406	Glyco_trans_14	Family

Pfam: PF02485

Enzyme classification (BRENDA):

• EC 2.4.1.150 — N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase (BRENDA: 14 organisms, 65 substrates, 15 inhibitors, 5 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GALBETA(1-4)GLCNACBETA(1-3)GALBETA(1-4)GLC	0.44	1
GALBETA(1-4)GLCNACBETA(1-3)GALBETA(1-4)GLCNACBET	0.55	1
NEUACALPHA(2-6)GALBETA(1-4)GLCNACBETA(1-3)GALBET	0.52	1
PYRIDYLAMINATED LACTO-N-NEOTETRAOSE	0.96	1
UDP-N-ACETYL-D-GLUCOSAMINE	2.59	1

Catalyzed reactions (Rhea), 1 shown:

• a beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + UDP-N-acetyl-alpha-D-glucosamine = a beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-[beta-D-GlcNAc-(1->6)]-beta-D-Gal-(1->4)-N-acetyl-beta-D-GlcNAc derivative + UDP + H(+) (RHEA:54820)

UniProt features (13 total): sequence variant 5, topological domain 2, splice variant 2, chain 1, sequence conflict 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0V5-F1	91.66	0.80

Functional residue map

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

Glycosylation sites (1): 41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, chr6p24, GOBP_REGULATION_OF_HETEROTYPIC_CELL_CELL_ADHESION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_CELL_SUBSTRATE_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (14): glycosaminoglycan biosynthetic process (GO:0006024), transforming growth factor beta receptor signaling pathway (GO:0007179), multicellular organism development (GO:0007275), positive regulation of cell population proliferation (GO:0008284), glycoprotein biosynthetic process (GO:0009101), post-transcriptional regulation of gene expression (GO:0010608), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of cell-substrate adhesion (GO:0010812), positive regulation of cell migration (GO:0030335), positive regulation of heterotypic cell-cell adhesion (GO:0034116), maintenance of lens transparency (GO:0036438), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase activity (GO:0008109), acetylglucosaminyltransferase activity (GO:0008375), protein binding (GO:0005515), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
multicellular organismal process	1
anatomical structure development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
regulation of gene expression	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
negative regulation of cell adhesion	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of cell-cell adhesion	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
tissue homeostasis	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
acetylglucosaminyltransferase activity	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
binding	1
glycosyltransferase activity	1
catalytic activity	1
transferase activity	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCNT2	B3GNT2	Q9NY97	876
GCNT2	GYPC	P04921	843
GCNT2	CRYBB3	P26998	815
GCNT2	TRNT1	Q96Q11	779
GCNT2	NHS	Q6T4R5	768
GCNT2	CRYGD	P07320	748
GCNT2	MGAT5	Q09328	685
GCNT2	CRYBB2	P43320	684
GCNT2	MGAT5B	Q3V5L5	667
GCNT2	MGAT2	Q10469	646
GCNT2	HSF4	Q9ULV5	636
GCNT2	MGAT4A	Q9UM21	616
GCNT2	ADGRL2	O95490	613
GCNT2	BFSP1	Q12934	607
GCNT2	MGAT4B	Q9UQ53	606

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TMEM79	GCNT2	psi-mi:“MI:0915”(physical association)	0.590
GCNT2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
GCNT2	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): ATP2A1 (Affinity Capture-MS), METTL9 (Affinity Capture-MS), GHITM (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), FAM3C (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), GCNT2 (Affinity Capture-MS), GCNT2 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), GHITM (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), FAM3C (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2C9JXL4, E9Q649, O95395, P0DN25, P97402, Q08BL3, Q0VC84, Q18515, Q24342, Q3SX46, Q499P3, Q5F3G7, Q5HZL5, Q5U258, Q5XJP0, Q5YB40, Q66GS2, Q6A1G2, Q6DE15, Q6DJR8, Q6GNL1, Q6P3P5, Q6P6V1, Q6WV16, Q6Y288, Q7K237, Q7SYI5, Q7T3S5, Q7Z1Z1, Q864U8, Q866Z5, Q8BGY6, Q8BHT6, Q8L7M1, Q8LPF8, Q8N0V5, Q8NCW6, Q96EU7, Q99NB2, Q9BYG0

Diamond homologs: A5GFW8, E9Q649, O95395, P97402, Q02742, Q09324, Q1M0V6, Q3V3K7, Q5JCT0, Q5U258, Q6ZNI0, Q71SG7, Q7YQE1, Q805R1, Q80RC7, Q866Z4, Q866Z5, Q866Z6, Q8CH87, Q8N0V5, Q92180, Q99CW3, Q9IZK2, Q9P109, Q5QQ53, Q7KVA1, Q5QQ54, Q5QQ55, A0A1U9VX91, A2BGL3, D4AUF1, D4AUF4, P54867, P83097, P84675, Q0IIY2, Q505J3, Q5QQ49, Q5QQ50, Q5QQ51

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	3
Uncertain significance	108
Likely benign	33
Benign	39

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1065633	NM_145649.5(GCNT2):c.14G>A (p.Trp5Ter)	Pathogenic
1437805	NM_145649.5(GCNT2):c.1000A>T (p.Arg334Ter)	Pathogenic
2424190	NC_000006.11:g.(?10556657)(10626840_?)del	Pathogenic
252954	NM_145649.5(GCNT2):c.1091T>C (p.Phe364Ser)	Pathogenic
2685194	GRCh37/hg19 6p24.3(chr6:10099993-10564232)x1	Pathogenic
2918140	NM_001491.3(GCNT2):c.760del (p.His254fs)	Pathogenic
4028900	NM_001491.3(GCNT2):c.760dup (p.His254fs)	Pathogenic
4279311	GRCh37/hg19 6p24.3-24.2(chr6:10535030-10630002)x1	Pathogenic
571035	NM_001491.3(GCNT2):c.60del (p.Ile20fs)	Pathogenic
571381	NM_001491.3(GCNT2):c.710_711insT (p.Lys237fs)	Pathogenic
685194	GRCh37/hg19 6p24.3-24.2(chr6:10541521-10645806)x1	Pathogenic
686169	GRCh37/hg19 6p24.3(chr6:10467100-10530991)x1	Pathogenic
686306	GRCh37/hg19 6p24.3(chr6:10528333-10575149)x1	Pathogenic
687321	GRCh37/hg19 6p24.3-24.2(chr6:10546386-10640180)x1	Pathogenic
687866	GRCh37/hg19 6p24.3(chr6:10483812-10560100)x1	Pathogenic
830705	NC_000006.12:g.(?10528892)(10557362_?)del	Pathogenic
830756	NC_000006.12:g.(?10556404)(10626627_?)del	Pathogenic
9128	NM_145649.5(GCNT2):c.1049G>A (p.Gly350Glu)	Pathogenic
9130	NM_001491.2(GCNT2):c.-117_*41del	Pathogenic
9131	NM_145649.5(GCNT2):c.505G>A (p.Ala169Thr)	Pathogenic
9132	NM_145649.5(GCNT2):c.683G>A (p.Arg228Gln)	Pathogenic
252955	NM_145649.5(GCNT2):c.1169_1172del (p.Asn390fs)	Likely pathogenic
4849340	NM_145649.5(GCNT2):c.651dup (p.Gly218fs)	Likely pathogenic
4849446	NM_001491.3(GCNT2):c.707_708dup (p.Lys237fs)	Likely pathogenic

SpliceAI

616 predictions. Top by Δscore:

Variant	Effect	Δscore
6:10586857:TCAA:T	donor_gain	0.9900
6:10586912:CAG:C	donor_loss	0.9900
6:10586913:AGGT:A	donor_loss	0.9900
6:10586915:G:GA	donor_loss	0.9900
6:10586916:T:A	donor_loss	0.9900
6:10621350:GGT:G	acceptor_gain	0.9900
6:10621439:CCACG:C	donor_loss	0.9900
6:10621440:CACGG:C	donor_loss	0.9900
6:10621441:ACGGT:A	donor_loss	0.9900
6:10621442:CGGTG:C	donor_loss	0.9900
6:10621443:GGTGA:G	donor_loss	0.9900
6:10621444:G:GA	donor_loss	0.9900
6:10621445:T:C	donor_loss	0.9900
6:10626411:TTGCA:T	acceptor_loss	0.9900
6:10626412:TGCA:T	acceptor_loss	0.9900
6:10626413:GCAG:G	acceptor_loss	0.9900
6:10626414:CAGGC:C	acceptor_loss	0.9900
6:10626415:A:AG	acceptor_gain	0.9900
6:10626415:AGGCC:A	acceptor_loss	0.9900
6:10626416:G:GA	acceptor_gain	0.9900
6:10626416:G:GT	acceptor_loss	0.9900
6:10626416:GGC:G	acceptor_gain	0.9900
6:10626416:GGCC:G	acceptor_gain	0.9900
6:10626416:GGCCA:G	acceptor_gain	0.9900
6:10586915:G:GG	donor_gain	0.9800
6:10621344:A:AG	acceptor_gain	0.9800
6:10621344:ATT:A	acceptor_gain	0.9800
6:10621345:TTGCA:T	acceptor_loss	0.9800
6:10621346:TGCA:T	acceptor_loss	0.9800
6:10621347:GCA:G	acceptor_loss	0.9800

AlphaMissense

2654 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:10621409:G:C	W328C	0.997
6:10621409:G:T	W328C	0.997
6:10621437:T:A	C338S	0.997
6:10621438:G:C	C338S	0.997
6:10626437:T:A	C347S	0.997
6:10626438:G:A	C347Y	0.997
6:10626438:G:C	C347S	0.997
6:10626439:T:G	C347W	0.997
6:10626499:G:C	K367N	0.997
6:10626499:G:T	K367N	0.997
6:10621407:T:A	W328R	0.996
6:10621407:T:C	W328R	0.996
6:10626437:T:C	C347R	0.996
6:10626438:G:T	C347F	0.996
6:10621437:T:C	C338R	0.994
6:10621438:G:A	C338Y	0.994
6:10626552:G:C	R385P	0.994
6:10529553:T:A	N214K	0.993
6:10529553:T:G	N214K	0.993
6:10529812:T:A	W301R	0.993
6:10529812:T:C	W301R	0.993
6:10621439:C:G	C338W	0.993
6:10626492:C:A	A365D	0.993
6:10626497:A:G	K367E	0.993
6:10621406:G:C	K327N	0.992
6:10621406:G:T	K327N	0.992
6:10626498:A:T	K367M	0.992
6:10621438:G:T	C338F	0.991
6:10626466:G:C	W356C	0.991
6:10626466:G:T	W356C	0.991

dbSNP variants (sampled 300 via entrez): RS1000000606 (6:10619883 A>G,T), RS1000030889 (6:10626003 T>A,C), RS1000031283 (6:10563253 T>G), RS1000092113 (6:10557499 T>G), RS1000106410 (6:10620105 A>G), RS1000121216 (6:10597762 A>G), RS1000121624 (6:10593389 G>A), RS1000123339 (6:10557680 A>T), RS1000185654 (6:10561514 T>C), RS1000186442 (6:10528084 G>C,T), RS1000194516 (6:10594751 C>T), RS1000210542 (6:10533094 G>A), RS1000239291 (6:10598021 A>C,G,T), RS1000245419 (6:10598693 T>C), RS1000285372 (6:10609535 G>A,T)

Disease associations

OMIM: gene MIM:600429 | disease phenotypes: MIM:116700

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 13 with adult I phenotype	Definitive	Autosomal recessive
total early-onset cataract	Supportive	Autosomal dominant

Mondo (2): cataract 13 with adult I phenotype (MONDO:0007289), total early-onset cataract (MONDO:0021548)

Orphanet (1): Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000519	Developmental cataract

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004609_60	Monocyte percentage of white cells	8.000000e-10
GCST004625_22	Monocyte count	4.000000e-18
GCST008153_65	Lean body mass	8.000000e-07
GCST008769_5	Perceived intensity of glucose	8.000000e-06
GCST009172_2	Response to (pegylated) interferon in HBeAg-negative hepatitis B	3.000000e-06
GCST90002388_108	Lymphocyte count	2.000000e-10
GCST90002393_8	Monocyte count	3.000000e-44
GCST90002394_37	Monocyte percentage of white cells	2.000000e-23
GCST90002407_233	White blood cell count	5.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004995	lean body mass
EFO:0007859	response to interferon
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
potassium chromate(VI)	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Formaldehyde	decreases expression	2
Smoke	decreases expression, increases expression	2
arsenite	increases methylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	increases expression	1
vanadyl sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	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
PCI 5002	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Azacitidine	decreases expression	1
Cisplatin	affects response to substance	1
Cytarabine	decreases expression	1
Diazinon	increases methylation	1
Bucladesine	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study