Structural eye disease

Gene: MAB21L1

Green List (high evidence)

Comment on list classification: Biallelic variants in MAB21L1 are associated with a syndromic phenotype including ophthalmological presentations such as horizontal nystagmus, bilateral corneal opacities/ corneal dystrophy, strabismus and retinal degeneration. These phenotypes are not relevant for this panel.

However, there is sufficient evidence available for the association of monoallelic MAB21L1 variants with phenotypes relevant to this panel such as microphthalmia and aniridia. Hence, this gene should be promoted to green rating with MOI set as 'MONOALLELIC' in the next GMS update.

Created: 12 May 2026, 6:02 p.m. | Last Modified: 12 May 2026, 6:02 p.m.

Panel Version: 5.5

PMID:27103078 (2017) reported the identification of a homozygous frameshift variant in MAB21L1 gene (p.Cys246Leufs*18) in a boy with scrotum agensis, ophthalmological anomalies, cerebellar malformation, facial dysmorphism and global developmental delay. Ocular anomalies included nystagmus, convergent strabismus and corneal dystrophy. There is also functional evidence available from knockout mice which presented a similar malformative association of ophthalmological malformations of the anterior chamber and preputial glands hypoplasia.

PMID:30487245 (2019) reported the identification of four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Ocular features included horizontal nystagmus, bilateral corneal opacities/ corneal dystrophy, strabismus and retinal degeneration.

PMID:33973683 (2021) reported a heterozygous novel variant in MAB21L1 gene (c.152G>T/ p.Arg51Leu), in two family members with microphthalmia and aniridia, as well as novel or rare compound heterozygous variants of uncertain significance (c.184C>T/ p.Arg62Cys; c.-68T>C and c.658G>C/ p.Gly220Arg; c.*529A>G) in two additional probands with microphthalmia, coloboma and/or cataracts. There is also function evidence available from in vitro studies of coding variants and in vivo complementation assays using the zebrafish mab21l2 Q48Sfs*5 loss-of-function line.

PMID:36413568 (2022) reported nine patients from five families with severe aniridia and/or microphthalmia with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. The detected variants are c.152G>A/ p.Arg51Gln, c.152G>T/ p.Arg51Leu, c.152G>C/ p.Arg51Pro and c.155T>G/ p.Phe52Cys. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes.

PMID:36446583 (2023) reported the identification of a novel missense variant (p.Phe52Leu) in a three-generation pedigree with autosomal dominant microphthalmia.

PMID:36892533 (2023) reported the identification of three heterozygous missense variants in MAB21L1 gene in five unrelated families, including c.152G>T/ p.Arg51Leu in two, c.152G>A/ p.Arg51Gln in two, and c.155T>G/ p.Phe52Cys in one. All patients presented with similar blepharophimosis plus anterior segment and macular dysgenesis (BAMD) phenotype.

PMID:39016008 (2024) reported an additional family with four individuals diagnosed with microphthalmia and with Arg51 variant in MAB21L1 gene.

Only biallelic variants in this gene are associated with relevant phenotypes in OMIM (MIM #618479, last accessed 12 May 2026), Gene2Phenotype (with 'definitive' rating on the DD and Eye panels) and ClinGen (Strong rating by Syndromic disorders Expert panel - https://search.clinicalgenome.org/CCID:008388) However, only monoallelic variants are associated with phenotypes relevant to this panel.
Sources: Literature

Created: 12 May 2026, 5:28 p.m. | Last Modified: 12 May 2026, 5:55 p.m.

Panel Version: 5.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
microphthalmia, MONDO:0021129; aniridia, MONDO:0019172

Publications

• 27103078
• 30487245
• 33973683
• 36413568
• 36446583
• 36892533
• 39016008