MAB21L1

Chr 13

mab-21 like 1

Also known as: CAGR1, COFG, Nbla00126

NCBI Gene: 4081 ENSG00000180660 UniProt: Q13394

MAB21L1 encodes a putative nucleotidyltransferase that binds single-stranded RNA and is required for normal embryonic development of the eye and other structures. Biallelic mutations cause cerebellar, ocular, craniofacial, and genital syndrome, which follows autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.628), consistent with its role in multiple developmental processes.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCerebellar, ocular, craniofacial, and genital syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Strong · cerebellar, ocular, craniofacial, and genital syndrome · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

LOF

Mechanism· G2P

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?

0.63LOEUF

pLI 0.286

Z-score 2.47

OE 0.24 (0.11–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.10Z-score

OE missense 0.78 (0.68–0.89)

150 obs / 193.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.11–0.63)

0≤0.351.4

Missense OE?0.78 (0.68–0.89)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 3 / 12.4Missense obs/exp: 150 / 193.2Syn Z: -2.02

Background carrier burden — how many people carry a rare variant somewhere in MAB21L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

427 rare PASS variants

Rare truncating (LoF)

1 in 16,000

25 rare PASS variants

Rare synonymous (reference)

1 in 370

227 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAB21L1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 13,000
South Asian	~43k	1 in 200	1 in 7,200
Remaining (unassigned)	~30k	1 in 270	none seen
European (Finnish)	~27k	1 in 260	≈ 1 in 8,800
Admixed American	~22k	1 in 180	≈ 1 in 22,000
African / African American	~21k	1 in 220	none seen
East Asian	~20k	1 in 180	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 4,400	none seen
Middle Eastern	~2,884	1 in 180	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓