ALG9

ALG9 alpha-1,2-mannosyltransferase, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases

Basic information

Region (hg38): 11:111782195-111871581

Previous symbols: [ "DIBD1" ]

Links

ENSG00000086848 ∙ NCBI:79796 ∙ OMIM:606941 ∙ HGNC:15672 ∙ Uniprot:Q9H6U8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant polycystic kidney disease (Moderate), mode of inheritance: AD
• ALG9-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG9-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• Gillessen-Kaesbach-Nishimura syndrome (Moderate), mode of inheritance: AR
• ALG9-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• autosomal dominant polycystic kidney disease (Supportive), mode of inheritance: AD
• ALG9-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• ALG9-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG9-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• ALG9-associated autosomal dominant polycystic kidney disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Il	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal	15148656; 15945070; 19451548; 25966638
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG9 gene.

• ALG9_congenital_disorder_of_glycosylation (210 variants)
• Gillessen-Kaesbach-Nishimura_syndrome (72 variants)
• not_provided (59 variants)
• ALG9-related_disorder (33 variants)
• not_specified (28 variants)
• Inborn_genetic_diseases (18 variants)
• Autosomal_dominant_polycystic_liver_disease (5 variants)
• ALG9-associated_autosomal_dominant_polycystic_kidney_disease (3 variants)
• Familial_cystic_renal_disease (2 variants)
• Polycystic_kidney_disease,_adult_type (2 variants)
• Congenital_disorder_of_glycosylation (1 variants)
• Gillessen-Kaesbach-Nishimura_dysplasia (1 variants)
• See_cases (1 variants)
• Autosomal_dominant_polycystic_kidney_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024740.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	49		53
missense	2	1	101	12	3	119
nonsense	5	6	2			13
start loss						0
frameshift	5	6				11
splice donor/acceptor (+/-2bp)		8	1			9
Total	12	21	108	61	3

Highest pathogenic variant AF is 0.0000712557

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG9	protein_coding	protein_coding	ENST00000531154	11	89387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000640	0.999	124776	0	20	124796	0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	190	233	0.814	0.0000120	2901
Missense in Polyphen		64	89.251	0.71708		1112
Synonymous	0.366	81	85.3	0.950	0.00000433	863
Loss of Function	2.91	10	26.0	0.385	0.00000137	308

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000209
Ashkenazi Jewish	0.0000997	0.0000993
East Asian	0.0000556	0.0000556
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.0000796	0.0000794
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosaccharides. {ECO:0000269|PubMed:15148656, ECO:0000269|PubMed:15945070}.
• Disease: DISEASE: Congenital disorder of glycosylation 1L (CDG1L) [MIM:608776]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:15148656, ECO:0000269|PubMed:15945070}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gillessen-Kaesbach-Nishimura syndrome (GIKANIS) [MIM:263210]: A rare autosomal recessive syndrome characterized by severe skeletal dysplasia, facial dysmorphic features, polycystic kidney disease and other visceral malformations. It may be lethal in utero or early in life. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. {ECO:0000269|PubMed:25966638}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.216

Intolerance Scores

• loftool: 0.881
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.1

Haploinsufficiency Scores

• pHI: 0.504
• hipred: N
• hipred_score: 0.488
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg9

Gene ontology

• Biological process: dolichol-linked oligosaccharide biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: alpha-1,2-mannosyltransferase activity;mannosyltransferase activity;dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity;dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity