FAM181B

Chr 11

family with sequence similarity 181 member B

The FAM181B protein functions as a component of the mitochondrial ribosome assembly machinery, specifically involved in the biogenesis of the large ribosomal subunit. Mutations cause autosomal recessive mitochondrial complex I deficiency with severe early-onset encephalomyopathy, characterized by developmental delay, seizures, hypotonia, and progressive neurodegeneration. The gene shows relatively low constraint against loss-of-function variants (pLI 0.07, LOEUF 1.49), consistent with its recessive inheritance pattern.

LOEUF 1.49
Clinical SummaryFAM181B
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 93 VUS of 110 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.49LOEUF
pLI 0.069
Z-score 0.93
OE 0.50 (0.201.49)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.09Z-score
OE missense 0.98 (0.861.12)
160 obs / 163.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.201.49)
00.351.4
Missense OE0.98 (0.861.12)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 2 / 4.0Missense obs/exp: 160 / 163.4Syn Z: -1.28

ClinVar Variant Classifications

110 submitted variants in ClinVar

Classification Summary

Pathogenic15
VUS93
Likely Benign2
15
Pathogenic
93
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
91
2
0
93
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total093170110

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM181B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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