GCNT2

protein-coding

glucosaminyl (N-acetyl) transferase 2 (I blood group), the group of Glucosaminyl (N-acetyl) transferases/xylosyltransferases|Blood group antigens

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

NACGT1
II
GCNT5
CCAT

MANE transcript

NM_145649.5

Inheritance

AR, AD, BG

ClinVar variants

P:13U:28B:11

Top phenotype

Blood group, Ii; Adult i phenotype without cataract

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr6:10,492,223-10,629,368

External References & Databases

Ensembl (ENSG00000111846)

Transcript & Mutation Effects

hg38 • Region Span ~137.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 13 with adult I phenotypeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0007289

Submitter: Ambry Genetics

cataract 13 with adult I phenotypeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007289

Submitter: PanelApp Australia

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

cataract 13 with adult I phenotypeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007289

Submitter: G2P

cataract 13 with adult I phenotypeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007289

Submitter: Labcorp Genetics (formerly Invitae)

cataract 13 with adult I phenotypeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0007289

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Blood group, Ii; Adult i phenotype without cataractBG/AR

Manifestation: Hematologic; Ophthalmologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 6858080; 3799539; 11739194; 12424189; 21912254

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GCNT2 variants in ClinVar

9 Conditions Cataloged

Cataract 13 with adult I phenotypeTotal: 39

Blood group, I systemTotal: 34

not providedTotal: 31

GCNT2-related disorderTotal: 30

Inborn genetic diseasesTotal: 20

not specifiedTotal: 6

Developmental cataractTotal: 2

ADULT i BLOOD GROUP PHENOTYPETotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145649.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	5 clinvar		7
missense	4 clinvar	4 clinvar	24 clinvar	6 clinvar		38
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	8	28	11	0	52

Highest pathogenic variant AF is 0.00016058072

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145649.5	RefSeq	NP_663624.1	3	MANE Select
ENST00000495262.7	Ensembl	ENSP00000419411.2	3	MANE Select
NM_001374747.1	RefSeq	NP_001361676.1	3	Standard
NM_001491.3	RefSeq	NP_001482.1	3	MANE Plus Clinical

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosphingolipid biosynthesis - lacto and neolacto series - Homo sapiens (human)
Glycosphingolipid biosynthesis - neolactoseries
terminal <i>O</i>-glycans residues modification

Biological Process

glycosaminoglycan biosynthetic process
protein glycosylation
transforming growth factor beta receptor signaling pathway
multicellular organism development
positive regulation of cell population proliferation

Molecular Function

N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase activity

Cellular Component

Golgi membrane
cellular_component
Golgi apparatus
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379597
Coding exons: 3
Length: 137146
Individuals with no LoFs: 125589
Homozygous LoFs: 0
Heterozygous LoFs: 159
Defined: 125748
p: 0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.10	262	216	1.21	0.0000120	2643
Missense (PolyPhen)		72	64.981	1.108		830
Synonymous	-1.28	105	89.6	1.17	0.00000578	783
Loss of Function	1.14	9	13.5	0.665	6.53e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0026	0.0026	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.0010	0.0010	notable
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:7579796, ECO:0000269|PubMed:8449405}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:11739194}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.159

Intolerance Scores

LoFtool: 0.977
RVIS EVS: -1.3
RVIS percentile EVS: 4.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.414

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium