MAB21L1
protein-codingmab-21 like 1, the group of MAB21 family
Gene summary
This gene is similar to the MAB-21 cell fate-determining gene found in C. elegans. It may be involved in eye and cerebellum development, and it has been proposed that expansion of a trinucleotide repeat region in the 5' UTR may play a role in a variety of psychiatric disorders. [provided by RefSeq, Oct 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032774
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032774
Submitter: ClinGen
The *MAB21L1* gene, located on chromosome 13 at 13q13.3, encodes the mab-21 like 1 protein which is a putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye. *MAB21L1* was first reported in relation to autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG) in 2017 (Bruel et al., PMID: 27103078). COFG is characterized by cerebellar hypoplasia with ataxia, ocular anomalies, facial dysmorphism, scrotal agenesis, absent or underdeveloped nipples and underdeveloped labioscrotal folds, accompanied by moderate to severe developmental delay and intellectual disability. The mechanism of disease is reported to be loss of function. At least six unique variants (missense, nonsense, frameshift) that have been reported in a homozygous statein 11 individuals from six consanguineous families in two publications (PMIDs: 27103078, 30487245) are included in this curation. Variants in this gene segregated in seven additional family members in two families (PMID: 30487245, 27075597). This gene-disease relationship is also supported by evidence of persistent and restricted expression of *Mab21l1* to the cerebellum and eye in mouse, and a mouse model which displayed eye and preputial gland anomalies (PMIDs: 10349626, 25434003). In summary, there is strong evidence to support the relationship between *MAB21L* and autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome. Three years must elapse from the first proposal of the assertion to reach a definitive classification without any valid contradictory evidence. We will re-evaluate this gene-disease relationship at that time to determine if an upgraded classification of definitive is warranted. This classification was approved by the ClinGen Syndromic GCEP on the meeting date April 19th, 2024 (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0032774
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032774
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0032774
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dermatologic; Genitourinary; Neurologic; Ophthalmologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAB21L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005584.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 7 | ||||
| missense | 2 | 2 | 34 | 1 | 39 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 6 | 3 | 34 | 8 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005575.1 | 1 | MANE Select | |
| Ensembl | ENSP00000369251.4 | 1 | MANE Select | |
| Ensembl | ENSP00000516753.1 | 1 | Standard | |
| Ensembl | ENSP00000621577.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of cell population proliferation
- anatomical structure morphogenesis
- camera-type eye development
Molecular Function
- protein binding
- ATP binding
- GTP binding
- nucleotidyltransferase activity
- metal ion binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379919
- Coding exons
- 1
- Length
- 2907
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 150 | 193 | 0.777 | 0.00000903 | 2342 |
| Missense (PolyPhen) | 33 | 72.763 | 0.45353 | 867 | ||
| Synonymous | -2.02 | 106 | 82.6 | 1.28 | 0.00000410 | 730 |
| Loss of Function | 2.47 | 3 | 12.4 | 0.243 | 5.47e-7 | 135 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye (By similarity). It is unclear whether it displays nucleotidyltransferase activity in vivo (PubMed:27271801). Binds single-stranded RNA (ssRNA) (PubMed:27271801). {ECO:0000250|UniProtKB:O70299, ECO:0000269|PubMed:27271801}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.274
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |