GANAB

Chr 11AD

glucosidase II alpha subunit

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

NCBI Gene: 23193 ENSG00000089597 UniProt: Q14697 OMIM: 104160

This gene encodes the catalytic subunit of glucosidase II, which cleaves glucose residues from immature glycoproteins in the endoplasmic reticulum and is required for proper maturation and localization of polycystin-1 and polycystin-2. Mutations cause autosomal dominant polycystic kidney disease 3, affecting the kidneys and liver. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Polycystic kidney disease 3MIM #600666

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · polycystic kidney disease 3 with or without polycystic liver disease · AD · ClinGen 2020

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

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Mechanism

📖

GeneReview available — GANAB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.16 (0.10–0.27)

0≤0.351.4

Missense OE?0.74 (0.68–0.80)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 10 / 63.5Missense obs/exp: 429 / 581.0Syn Z: -1.32

Background carrier burden — how many people carry a rare variant somewhere in GANAB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,032 rare PASS variants

Rare truncating (LoF)

1 in 3,600

83 rare PASS variants

Rare synonymous (reference)

1 in 100

530 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GANAB. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 4,500
South Asian	~43k	1 in 76	1 in 5,400
Remaining (unassigned)	~30k	1 in 52	1 in 6,000
European (Finnish)	~27k	1 in 330	1 in 4,400
Admixed American	~22k	1 in 46	≈ 1 in 7,400
African / African American	~21k	1 in 64	1 in 1,800
East Asian	~20k	1 in 96	1 in 3,300
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 58	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 22 of 24 coding exons well covered in gnomAD exomes; exons 8, 18 marginal. Genomes: all 24.? see exons ↓