MAB21L4

Chr 2

mab-21 like 4

Also known as: C2orf54

NCBI Gene: 79919 ENSG00000172478 UniProt: Q08AI8

The protein is a transcription factor that regulates early embryonic development and cellular differentiation. Mutations cause autosomal recessive intellectual disability with distinctive facial features, developmental delay, and growth retardation. This gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.53

LOEUF

GOF

Mechanism· predicted

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?

1.53LOEUF

pLI 0.000

Z-score 0.16

OE 0.95 (0.61–1.53)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.08Z-score

OE missense 1.01 (0.92–1.12)

269 obs / 265.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.61–1.53)

0≤0.351.4

Missense OE?1.01 (0.92–1.12)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 12 / 12.6Missense obs/exp: 269 / 265.3Syn Z: 0.84

Background carrier burden — how many people carry a rare variant somewhere in MAB21L4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

703 rare PASS variants

Rare truncating (LoF)

1 in 1,700

86 rare PASS variants

Rare synonymous (reference)

1 in 76

306 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAB21L4. 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 66	1 in 2,500
South Asian	~43k	1 in 53	1 in 710
Remaining (unassigned)	~30k	1 in 54	1 in 2,300
European (Finnish)	~27k	1 in 170	1 in 2,700
Admixed American	~22k	1 in 55	≈ 1 in 8,400
African / African American	~21k	1 in 48	1 in 1,100
East Asian	~20k	1 in 75	≈ 1 in 9,600
Ashkenazi Jewish	~13k	1 in 270	1 in 1,700
Middle Eastern	~2,884	1 in 44	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓