ATOSB

Chr 9

atos homolog B

Also known as: FAM214B, KIAA1539

NCBI Gene: 80256 ENSG00000005238 UniProt: Q7L5A3 OMIM: 620169

This nuclear transcription regulator synchronizes transcriptional and translational programs and is highly constrained against loss-of-function variants (pLI=0.80, LOEUF=0.42). Mutations in ATOSB cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.802

Z-score 3.34

OE 0.16 (0.07–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.22Z-score

OE missense 0.81 (0.73–0.90)

253 obs / 313.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.07–0.42)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 3 / 18.5Missense obs/exp: 253 / 313.6Syn Z: 0.89

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

671 rare PASS variants

Rare truncating (LoF)

1 in 2,800

58 rare PASS variants

Rare synonymous (reference)

1 in 200

284 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATOSB. 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 92	1 in 3,400
South Asian	~43k	1 in 71	1 in 2,100
Remaining (unassigned)	~30k	1 in 64	1 in 4,900
European (Finnish)	~27k	1 in 240	1 in 1,200
Admixed American	~22k	1 in 84	1 in 900
African / African American	~21k	1 in 67	1 in 2,800
East Asian	~20k	1 in 82	1 in 3,300
Ashkenazi Jewish	~13k	1 in 250	none seen
Middle Eastern	~2,884	1 in 110	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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓