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; nuclear speck; and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— FAM193B

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

137 VUS of 162 total submissions

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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

This gene — mechanism propensity

0.3395th %ile

GOF

0.3887th %ile

LOF

0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

VUS137

Likely Benign5

137

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	137	0	137
Likely Benign	4	1	5
Benign	0	0	0
Total	141	1	142

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

58 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap FAM193B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →