FAM181B

Chr 11

family with sequence similarity 181 member B

NCBI Gene: 220382 ENSG00000182103 UniProt: A6NEQ2

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.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.49

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.49LOEUF

pLI 0.069

Z-score 0.93

OE 0.50 (0.20–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.86–1.12)

160 obs / 163.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.20–1.49)

0≤0.351.4

Missense OE?0.98 (0.86–1.12)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 2 / 4.0Missense obs/exp: 160 / 163.4Syn Z: -1.28

Background carrier burden — how many people carry a rare variant somewhere in FAM181B?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

781 rare PASS variants

Rare truncating (LoF)

1 in 4,700

67 rare PASS variants

Rare synonymous (reference)

1 in 170

365 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM181B. 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 120	1 in 6,200
South Asian	~43k	1 in 68	1 in 5,300
Remaining (unassigned)	~30k	1 in 71	≈ 1 in 12,000
European (Finnish)	~26k	1 in 200	1 in 1,900
Admixed American	~22k	1 in 86	1 in 2,800
African / African American	~21k	1 in 58	≈ 1 in 10,000
East Asian	~20k	1 in 84	1 in 2,500
Ashkenazi Jewish	~13k	1 in 680	≈ 1 in 8,700
Middle Eastern	~2,884	1 in 66	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): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 1.? see exons ↓