MANBA

Chr 4

mannosidase beta

Also known as: MANB1

NCBI Gene: 4126ENSG00000109323UniProt: O00462

This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtMannosidosis, beta A, lysosomal
488
ClinVar variants
83
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MANBA
🧬
Gene-Disease Validity (ClinGen)
beta-mannosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 104 VUS of 488 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.96LOEUF
pLI 0.000
Z-score 1.75
OE 0.73 (0.56–0.96)
Tolerant

Typical tolerance to LoF variation

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.
0.05Z-score
OE missense 0.99 (0.92–1.07)
468 obs / 471.0 exp
Tolerant

Mild missense constraint

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.0.73 (0.56–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.92–1.07)
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.0.96
0≤1.21.6
LoF obs/exp: 35 / 48.1Missense obs/exp: 468 / 471.0Syn Z: 0.36

ClinVar Variant Classifications

488 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic31
VUS104
Likely Benign295
Benign3
Conflicting3
52
Pathogenic
31
Likely Pathogenic
104
VUS
295
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
0
28
0
52
Likely Pathogenic
19
1
11
0
31
VUS
2
96
6
0
104
Likely Benign
0
1
112
182
295
Benign
0
0
3
0
3
Conflicting
—3
Total4598160182488

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

View in ClinVar →

Protein Context — Lollipop Plot

MANBA · protein map & ClinVar variants

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

Gene2Phenotype Curations

MANBA-related lysosomal beta-mannosidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variant c.2158-2A>G in MANBA is an important and frequent cause of hereditary hearing loss and beta-mannosidosis among the Czech and Slovak Roma population- evidence for a new ethnic-specific variant.
Safka Brozkova D et al.·Orphanet J Rare Dis
2020
NFKB1 and MANBA Confer Disease Susceptibility to Primary Biliary Cholangitis via Independent Putative Primary Functional Variants.
Hitomi Y et al.·Cell Mol Gastroenterol Hepatol
2019Functional
Impact of Multiple Sclerosis Risk Polymorphism rs7665090 on MANBA Activity, Lysosomal Endocytosis, and Lymphocyte Activation.
González-Jiménez A et al.·Int J Mol Sci
2022
A novel genetic variant potentially altering the expression of MANBA in the cerebellum associated with attention deficit hyperactivity disorder in Han Chinese children.
Chen X et al.·World J Biol Psychiatry
2022
A meta-analysis of genome-wide association studies of epigenetic age acceleration.
Gibson J et al.·PLoS Genet
2019
Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis.
Han Y et al.·Nat Commun
2023
eQTL colocalization analysis highlights novel susceptibility genes in Autism Spectrum Disorders (ASD).
Dominguez-Alonso S et al.·Transl Psychiatry
2023
β-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA.
Blomqvist M et al.·Cold Spring Harb Mol Case Stud
2019Case report
Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation.
Molho-Pessach V et al.·J Am Acad Dermatol
2007Review
Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics.
Xing J et al.·Front Immunol
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