FAM193B

Chr 5

family with sequence similarity 193 member B

Also known as: IRIZIO

NCBI Gene: 54540 ENSG00000146067 UniProt: Q96PV7 OMIM: 615813

The protein is localized to the cytoplasm, nuclear speckles, and nucleolus, though its specific molecular function remains unclear. Mutations in this gene cause developmental and epileptic encephalopathy, typically presenting in infancy with seizures and developmental delays. The condition follows an autosomal dominant inheritance pattern, and the gene is highly constrained against loss-of-function mutations.

OMIM ResearchSummary from RefSeq

Located in cytoplasm; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

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

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.993

Z-score 4.39

OE 0.11 (0.05–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.83Z-score

OE missense 0.88 (0.81–0.96)

345 obs / 391.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.28)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 3 / 28.1Missense obs/exp: 345 / 391.3Syn Z: 0.03

Background carrier burden — how many people carry a rare variant somewhere in FAM193B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,175 rare PASS variants

Rare truncating (LoF)

1 in 2,300

98 rare PASS variants

Rare synonymous (reference)

1 in 60

530 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM193B. 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 70	1 in 3,000
South Asian	~43k	1 in 43	1 in 2,600
Remaining (unassigned)	~30k	1 in 47	1 in 4,200
European (Finnish)	~27k	1 in 110	1 in 910
Admixed American	~22k	1 in 41	1 in 2,000
African / African American	~21k	1 in 57	≈ 1 in 4,600
East Asian	~20k	1 in 46	≈ 1 in 9,200
Ashkenazi Jewish	~13k	1 in 170	1 in 360
Middle Eastern	~2,884	1 in 41	≈ 1 in 1,100

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓