GCNT2

Chr 6ADAR

glucosaminyl (N-acetyl) transferase 2 (I blood group)

Also known as: CCAT, CTRCT13, GCNT2C, GCNT5, IGNT, II, NACGT1, NAGCT1

NCBI Gene: 2651ENSG00000111846UniProt: Q8N0V5

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]

Primary Disease Associations & Inheritance

[Blood group, Ii]MIM #110800
AD
Adult i phenotype without cataractMIM #110800
AD
Cataract 13 with adult i phenotypeMIM #116700
AR
UniProtCataract 13, with adult i phenotype
247
ClinVar variants
49
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GCNT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 119 VUS of 247 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 1.14
OE 0.67 (0.40–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.10Z-score
OE missense 1.21 (1.09–1.34)
262 obs / 216.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.40–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.21 (1.09–1.34)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 9 / 13.5Missense obs/exp: 262 / 216.5Syn Z: -1.28

ClinVar Variant Classifications

247 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic5
VUS119
Likely Benign36
Benign39
Conflicting4
44
Pathogenic
5
Likely Pathogenic
119
VUS
36
Likely Benign
39
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
4
36
0
44
Likely Pathogenic
1
1
3
0
5
VUS
3
44
69
3
119
Likely Benign
0
5
19
12
36
Benign
0
4
30
5
39
Conflicting
—4
Total85815720247

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GCNT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GCNT2-related cataract with adult i phenotype

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

[Blood group, Ii]

MIM #110800

Molecular basis of disorder known

Autosomal dominant

Adult i phenotype without cataract

MIM #110800

Molecular basis of disorder known

Autosomal dominant

Cataract 13 with adult i phenotype

MIM #116700

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hypomethylation of GCNT2 isoform A correlates with transcriptional expression and is associated with poor survival in acute myeloid leukemia.
Wu DH et al.·Front Immunol
2025
Loss of GCNT2/I-branched glycans enhances melanoma growth and survival.
Sweeney JG et al.·Nat Commun
2018
Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.
Nakamura K et al.·Anticancer Res
2015
Inhibition of miR-199b-5p reduces pathological alterations in osteoarthritis by potentially targeting Fzd6 and Gcnt2.
Feng T et al.·Elife
2024
Gastric Cancer Heterogeneity and Clinical Outcomes.
Sexton RE et al.·Technol Cancer Res Treat
2020
Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts.
Huang Y et al.·Sci Rep
2025
Case report of homozygous deletion involving the first coding exons of GCNT2 isoforms A and B and part of the upstream region of TFAP2A in congenital cataract.
Happ H et al.·BMC Med Genet
2016Case report
Genome-Wide Blood DNA Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen-Specific Immunotherapy.
Lahnsteiner A et al.·Allergy
2025Cohort
Blood biochemical landscape and new insights into clinical decision-making for polycystic ovary syndrome in Chinese women: a prospective cohort study.
Li Y et al.·Front Endocrinol (Lausanne)
2025Cohort
Hematologic biomarkers in childhood cataracts.
Wussuki-Lior O et al.·Mol Vis
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools