MAN1B1

mannosidase alpha class 1B member 1, the group of Mannosidases alpha class 1

Basic information

Region (hg38): 9:137086856-137109189

Links

ENSG00000177239 ∙ NCBI:11253 ∙ OMIM:604346 ∙ HGNC:6823 ∙ Uniprot:Q9UKM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Rafiq syndrome (Strong), mode of inheritance: AR
• Rafiq syndrome (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• MAN1B1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• Rafiq syndrome (Strong), mode of inheritance: AR
• MAN1B1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rafiq syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	20345473; 21763484; 21063731

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAN1B1 gene.

• Rafiq syndrome (335 variants)
• Inborn genetic diseases (150 variants)
• not provided (111 variants)
• not specified (43 variants)
• Intellectual Disability, Recessive (4 variants)
• Intellectual disability (2 variants)
• Seizure (2 variants)
• MAN1B1-congenital disorder of glycosylation (1 variants)
• Global developmental delay (1 variants)
• MAN1B1-Related Disorders (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAN1B1 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			15	70	5	90
missense	1	4	170	8	5	188
nonsense	8	3				11
start loss						0
frameshift	4	4				8
inframe indel			3	4		7
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	8	10	4	23
non coding			19	45	36	100
Total	14	13	207	127	46

Highest pathogenic variant AF is 0.0000593

Variants in MAN1B1

This is a list of pathogenic ClinVar variants found in the MAN1B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-137086979-C-A		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
9-137087006-G-T		Rafiq syndrome • Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
9-137087008-C-G		Inborn genetic diseases • Rafiq syndrome	Likely benign (Dec 01, 2023)
9-137087008-C-T		Rafiq syndrome	Likely benign (Feb 15, 2023)
9-137087014-G-A		Rafiq syndrome	Likely benign (Jun 20, 2022)
9-137087018-A-G		Inborn genetic diseases	Uncertain significance (Jul 31, 2017)
9-137087025-G-C		Rafiq syndrome • Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
9-137087027-G-C		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
9-137087030-G-A		Rafiq syndrome	Benign (Dec 13, 2023)
9-137087032-T-C		Inborn genetic diseases	Likely benign (Oct 23, 2019)
9-137087035-C-G		Rafiq syndrome	Likely benign (Dec 18, 2023)
9-137087035-C-T		Inborn genetic diseases • Rafiq syndrome	Likely benign (Aug 17, 2023)
9-137087037-G-C		Rafiq syndrome	Uncertain significance (Nov 24, 2022)
9-137087040-C-T		Rafiq syndrome	Uncertain significance (Jan 12, 2018)
9-137087041-C-T		Rafiq syndrome	Likely benign (Nov 19, 2023)
9-137087048-T-C		Rafiq syndrome	Uncertain significance (Apr 19, 2022)
9-137087064-C-T		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
9-137087074-C-CG		Rafiq syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 13, 2018)
9-137087077-G-C		Rafiq syndrome	Likely benign (Oct 13, 2023)
9-137087087-G-C		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
9-137087089-C-G			Likely benign (Oct 05, 2017)
9-137087100-C-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
9-137087101-T-C		Rafiq syndrome	Likely benign (Dec 03, 2023)
9-137087110-G-C		Inborn genetic diseases	Uncertain significance (Jun 27, 2023)
9-137087113-CCCA-C		Inborn genetic diseases	Likely benign (Jul 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAN1B1	protein_coding	protein_coding	ENST00000371589	13	22257

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.18e-8	0.986	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.726	448	407	1.10	0.0000258	4534
Missense in Polyphen		107	129.38	0.82705		1480
Synonymous	-3.25	237	181	1.31	0.0000125	1393
Loss of Function	2.31	18	32.1	0.560	0.00000149	367

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000866	0.000865
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.000232	0.000229
Middle Eastern	0.000218	0.000217
South Asian	0.000137	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2). {ECO:0000269|PubMed:12090241, ECO:0000269|PubMed:18003979}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);er associated degradation (erad) pathway;ER Quality Control Compartment (ERQC);Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;N-Glycan biosynthesis (Consensus)

Intolerance Scores

• loftool: 0.409
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.29

Haploinsufficiency Scores

• pHI: 0.317
• hipred: N
• hipred_score: 0.206
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.194

Mouse Genome Informatics

• Gene name: Man1b1

Gene ontology

• Biological process: protein glycosylation;N-glycan processing;oligosaccharide metabolic process;ubiquitin-dependent ERAD pathway;protein alpha-1,2-demannosylation;trimming of terminal mannose on B branch;trimming of terminal mannose on C branch;trimming of first mannose on A branch;trimming of second mannose on A branch;endoplasmic reticulum mannose trimming;mannose trimming involved in glycoprotein ERAD pathway
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;membrane;integral component of membrane;endoplasmic reticulum quality control compartment;extracellular vesicle
• Molecular function: mannosyl-oligosaccharide 1,2-alpha-mannosidase activity;calcium ion binding