MAN1B1
Chr 9ARmannosidase alpha class 1B member 1
Also known as: ERMAN1, ERManI, MANA-ER, MRT15
This gene encodes an alpha-1,2-mannosidase that trims mannose residues from N-linked glycans in the endoplasmic reticulum, functioning in glycoprotein quality control and targeting misfolded proteins for degradation. Biallelic mutations cause Rafiq syndrome, an autosomal recessive intellectual disability disorder. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.83), suggesting some tolerance to heterozygous disruption.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
652 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 18 | 0 | 80 | 0 | 98 |
Likely Pathogenic | 14 | 4 | 6 | 0 | 24 |
VUS | 0 | 203 | 26 | 6 | 235 |
Likely Benign | 1 | 15 | 81 | 95 | 192 |
Benign | 0 | 5 | 41 | 4 | 50 |
Conflicting | — | 40 | |||
| Total | 33 | 227 | 234 | 105 | 639 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MAN1B1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools