GANAB

glucosidase II alpha subunit, the group of Glycoside hydrolase family 31

Basic information

Region (hg38): 11:62624826-62646726

Links

ENSG00000089597 ∙ NCBI:23193 ∙ OMIM:104160 ∙ HGNC:4138 ∙ Uniprot:Q14697 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic kidney disease 3 with or without polycystic liver disease (Strong), mode of inheritance: AD
• autosomal dominant polycystic kidney disease (Supportive), mode of inheritance: AD
• polycystic kidney disease 3 with or without polycystic liver disease (Strong), mode of inheritance: AD
• polycystic kidney disease 3 with or without polycystic liver disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polycystic kidney disease 3 with or without polycystic liver disease	AD	Cardiovascular; Gastrointestinal; Renal	A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial	Cardiovascular; Gastrointestinal; Renal	27259053

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GANAB gene.

• not provided (5 variants)
• Polycystic kidney disease 3 with or without polycystic liver disease (2 variants)
• POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GANAB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	53	5	64
missense		2	129	16	7	154
nonsense	1	6	1			8
start loss						0
frameshift	5	3				8
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1					1
splice region		1	4	6		11
non coding		1	4	46	16	67
Total	7	12	144	115	28

Variants in GANAB

This is a list of pathogenic ClinVar variants found in the GANAB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-62625819-C-G		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
11-62625820-G-A		Polycystic kidney disease 3 with or without polycystic liver disease	Uncertain significance (May 26, 2020)
11-62625844-C-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
11-62625849-T-C			Uncertain significance (Oct 06, 2023)
11-62625864-C-T			Uncertain significance (Nov 18, 2022)
11-62625865-G-A			Uncertain significance (Aug 02, 2022)
11-62625881-G-C		GANAB-related disorder	Likely benign (Aug 04, 2020)
11-62625885-T-C			Uncertain significance (Jul 01, 2024)
11-62625900-A-C			Uncertain significance (Oct 13, 2023)
11-62625910-G-A		GANAB-related disorder	Benign (Sep 17, 2023)
11-62625937-T-C			Likely benign (Aug 16, 2022)
11-62625937-TAA-T			Likely benign (Dec 13, 2023)
11-62626052-ATTGGTCACT-A		POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE	Pathogenic (Feb 21, 2018)
11-62626073-T-C			Uncertain significance (-)
11-62626088-G-A			Likely benign (Apr 07, 2023)
11-62626097-C-G			Uncertain significance (Aug 28, 2018)
11-62626106-A-G			Uncertain significance (Apr 05, 2022)
11-62626118-C-T		Inborn genetic diseases	Uncertain significance (Jul 29, 2023)
11-62626154-G-A		Autosomal dominant polycystic liver disease	Benign (Sep 01, 2021)
11-62626319-G-A			Likely benign (Jan 09, 2023)
11-62626324-T-G			Likely benign (Sep 10, 2023)
11-62626327-CCCATTA-C		POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE	Pathogenic (Feb 06, 2023)
11-62626330-A-G			Uncertain significance (Mar 11, 2023)
11-62626342-C-T			Uncertain significance (Jun 09, 2022)
11-62626368-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GANAB	protein_coding	protein_coding	ENST00000346178	25	21807

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00127	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	429	581	0.738	0.0000342	6269
Missense in Polyphen		101	214.98	0.46981		2391
Synonymous	-1.32	238	213	1.11	0.0000113	1930
Loss of Function	6.22	10	63.5	0.158	0.00000402	605

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, ECO:0000269|PubMed:27259053}.
• Disease: DISEASE: Note=GANAB variations may act as a disease modifier in autosomal dominant polycystic liver disease in patients who have causative mutations in other genes, such as PKHD1 or ALG8. {ECO:0000269|PubMed:28375157}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);er associated degradation (erad) pathway;Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Galactose metabolism;Asparagine N-linked glycosylation;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.0310
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.02

Haploinsufficiency Scores

• pHI: 0.374
• hipred: Y
• hipred_score: 0.568
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.558

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ganab

Gene ontology

• Biological process: carbohydrate metabolic process;N-glycan processing
• Cellular component: endoplasmic reticulum lumen;Golgi apparatus;membrane;glucosidase II complex;melanosome;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: RNA binding;protein binding;carbohydrate binding;glucan 1,3-alpha-glucosidase activity