GANAB

Chr 11AD

glucosidase II alpha subunit

Also known as: G2AN, GIIA, GIIalpha, GLUII, PKD3

NCBI Gene: 23193ENSG00000089597UniProt: Q14697

This gene encodes the alpha subunit of glucosidase II and a member of the glycosyl hydrolase 31 family of proteins. The heterodimeric enzyme glucosidase II plays a role in protein folding and quality control by cleaving glucose residues from immature glycoproteins in the endoplasmic reticulum. Expression of the encoded protein is elevated in lung tumor tissue and in response to UV irradiation. Mutations in this gene cause autosomal-dominant polycystic kidney and liver disease. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

Polycystic kidney disease 3MIM #600666
AD
418
ClinVar variants
58
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GANAB
🧬
Gene-Disease Validity (ClinGen)
polycystic kidney disease 3 with or without polycystic liver disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 215 VUS of 418 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.27LOEUF
pLI 0.999
Z-score 6.22
OE 0.16 (0.10–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.24Z-score
OE missense 0.74 (0.68–0.80)
429 obs / 581.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.16 (0.10–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.68–0.80)
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.1.11
0≤1.21.6
LoF obs/exp: 10 / 63.5Missense obs/exp: 429 / 581.0Syn Z: -1.32

ClinVar Variant Classifications

418 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic33
VUS215
Likely Benign114
Benign14
Conflicting17
25
Pathogenic
33
Likely Pathogenic
215
VUS
114
Likely Benign
14
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
3
13
0
25
Likely Pathogenic
16
6
11
0
33
VUS
0
187
19
9
215
Likely Benign
0
10
41
63
114
Benign
0
7
4
3
14
Conflicting
—17
Total252138875418

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

View in ClinVar →

Protein Context — Lollipop Plot

GANAB · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Polycystic kidney disease 3

MIM #600666

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — GANAB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis.
Fu K et al.·EBioMedicine
2024
Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.
Senum SR et al.·Am J Hum Genet
2022
Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
Yang H et al.·Adv Kidney Dis Health
2023Review
Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.
Chang AR et al.·JAMA
2022
Isolated polycystic liver disease genes define effectors of polycystin-1 function.
Besse W et al.·J Clin Invest
2017
Genomic diagnostics in polycystic kidney disease: an assessment of real-world use of whole-genome sequencing.
Mallawaarachchi AC et al.·Eur J Hum Genet
2021
Molecular Diagnosis and Identification of Novel Pathogenic Variants in a Large Cohort of Italian Patients Affected by Polycystic Kidney Diseases.
Nigro E et al.·Genes (Basel)
2023Cohort
Novel mutations of PKD genes in Chinese patients suffering from autosomal dominant polycystic kidney disease and seeking assisted reproduction.
He WB et al.·BMC Med Genet
2018Cohort
GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review.
De Masi R et al.·Int J Mol Sci
2022Review
AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry.
Zhang Y et al.·Autophagy
2024
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