FAM133A

Chr X

family with sequence similarity 133 member A

Also known as: CT115

NCBI Gene: 286499 ENSG00000179083 UniProt: Q8N9E0

The FAM133A protein function is not well characterized. Mutations cause autosomal recessive developmental and epileptic encephalopathy with progressive microcephaly, typically with onset in infancy. The gene shows relatively low constraint to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

Research

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

0.95

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.396

Z-score 1.66

OE 0.20 (0.07–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.80–1.20)

64 obs / 65.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.07–0.95)

0≤0.351.4

Missense OE?0.98 (0.80–1.20)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 5.0Missense obs/exp: 64 / 65.6Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in FAM133A?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 530

177 rare PASS variants

Rare truncating (LoF)

1 in 4,900

34 rare PASS variants

Rare synonymous (reference)

1 in 1,600

67 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM133A. 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)	~561k	1 in 770	1 in 4,600
South Asian	~36k	1 in 470	1 in 1,500
Remaining (unassigned)	~31k	1 in 540	1 in 960
European (Finnish)	~27k	1 in 1,600	≈ 1 in 27,000
Admixed American	~23k	1 in 390	≈ 1 in 11,000
African / African American	~21k	1 in 270	1 in 3,500
East Asian	~20k	1 in 500	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 3,900	none seen
Middle Eastern	~2,751	1 in 510	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 ↓