Human Gene Module / Chromosome 9 / MAN1B1

MAN1B1mannosidase alpha class 1B member 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
27 / 0
Aliases
-
Associated Syndromes
Rafiq syndrome, Rafiq syndrome, DD, ID
Chromosome Band
9q34.3
Associated Disorders
-
Relevance to Autism

Whole-exome sequencing of a Turkish cohort of 62 children diagnosed with ASD or at risk for ASD in Eser et al., 2025 identified a homozygous missense variant in the MAN1B1 gene (p.Arg334Cys) in a 7-year-old male born to consanguineous parents; this variant has previously been shown to cause reduced protein expression and other functional deficits in both HEK293 cells and patient-derived fibroblasts (Rafiq et al., 2011; Rymen et al., 2013). A different homozygous missense variant in MAN1B1 (p.Val633Phe) had previously been reported in a female ASD proband from Saudi Arabia (Al-Mubarak et al., 2017). A diagnosis of ASD was made in one of seven individuals presenting with Rafiq syndrome in Rymen et al., 2013, while behavioral abnormalities (including autistic features) were observed in a subset of 12 individuals with Rafiq syndrome described in Van Scherpenzeel et al., 2014. De novo and inherited heterozygous variants in this gene have also been observed in ASD probands from the MSSNG cohort, the SPARK cohort, and the mAGRE cohort (Yuen et al., 2017; Trost et al., 2022; Cirnigliaro et al., 2023).

Molecular Function

This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause a form of autosomal-recessive intellectual disability (Rafiq syndrome, OMIM 614202) (Rafiq et al., 2011).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
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Reports related to MAN1B1 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Muhammad Arshad Rafiq et al. (2011) No -
2 Support - et al. () No ASD, epilepsy/seizures
3 Support - Monique Van Scherpenzeel et al. (2014) No Autistic features, epilepsy/seizures
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
5 Support Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families Al-Mubarak B , et al. (2017) Yes -
6 Support - Trost B et al. (2022) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
8 Primary - Metin Eser et al. (2025) Yes -
Rare Variants   (27)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.465+1460_620+527del - copy_number_loss De novo - Simplex 24348268 et al. ()
c.172G>T p.Glu58Ter stop_gained Familial Maternal Simplex 24348268 et al. ()
c.1225T>C p.Ser409Pro missense_variant Familial Paternal Simplex 24348268 et al. ()
c.1445+2_1445+5del - splice_site_variant Familial Maternal Simplex 24348268 et al. ()
c.1833_1834delAG - frameshift_variant Familial Both parents Simplex 24348268 et al. ()
c.2053G>T p.Val685Leu missense_variant De novo - Simplex 36368308 Trost B et al. (2022)
c.1000C>T p.Arg334Cys missense_variant Familial Both parents Simplex 24348268 et al. ()
c.1225T>C p.Ser409Pro missense_variant Familial Both parents Simplex 24348268 et al. ()
c.2099A>G p.Ter700TrpextTer38 stop_lost De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1000C>T p.Arg334Cys missense_variant Familial Both parents Multiplex 24348268 et al. ()
c.621-2A>G - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1849C>T p.Gln617Ter stop_gained Unknown - Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1001G>C p.Arg334Pro missense_variant Unknown - Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1000C>T p.Arg334Cys missense_variant Familial Both parents Multiplex 41420732 Metin Eser et al. (2025)
c.1897G>T p.Val633Phe missense_variant Familial Both parents Simplex 28720891 Al-Mubarak B , et al. (2017)
c.621-2A>G - splice_site_variant Familial Paternal Multiplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.224G>A p.Trp75Ter stop_gained Familial Both parents Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.2065G>T p.Glu689Ter stop_gained Familial Both parents Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1225T>C p.Ser409Pro missense_variant Familial Paternal Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1863G>A p.Trp621Ter stop_gained Familial Both parents Multiplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1789C>T p.Arg597Trp missense_variant Familial Maternal Multiplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.2065G>A p.Glu689Lys missense_variant Familial Paternal Multiplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.719_720del p.Gln240ArgfsTer15 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1000C>T p.Arg334Cys missense_variant Familial Both parents Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1976T>G p.Phe659Cys missense_variant Familial Both parents Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.1282delA p.Ile428fsTer43 frameshift_variant Familial Maternal Simplex 24566669 Monique Van Scherpenzeel et al. (2014)
c.530_542del p.Leu177ProfsTer32 frameshift_variant Familial Maternal Multiplex 24566669 Monique Van Scherpenzeel et al. (2014)
Common Variants  

No common variants reported.

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