FAM193B

Chr 5

family with sequence similarity 193 member B

Also known as: IRIZIO

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.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
0.28
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryFAM193B
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.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 148 VUS of 230 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.993
Z-score 4.39
OE 0.11 (0.050.28)
Highly constrained

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

Missense Constraint
0.83Z-score
OE missense 0.88 (0.810.96)
345 obs / 391.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.050.28)
00.351.4
Missense OE0.88 (0.810.96)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 3 / 28.1Missense obs/exp: 345 / 391.3Syn Z: 0.03
DN
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

230 submitted variants in ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic5
VUS148
Likely Benign6
51
Pathogenic
5
Likely Pathogenic
148
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
5
0
5
VUS
0
137
11
0
148
Likely Benign
0
4
1
1
6
Benign
0
0
0
0
0
Total0141681210

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM193B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found