FEM1B

Chr 15

fem-1 homolog B

Also known as: F1A-ALPHA, F1AA, FEM1-beta, NEDBES

NCBI Gene: 10116 ENSG00000169018 UniProt: Q9UK73

This gene encodes an ankyrin repeat protein that belongs to the death receptor-associated family of proteins and plays a role in mediating apoptosis. The encoded protein is also thought to function in the replication stress-induced checkpoint signaling pathway via interaction with checkpoint kinase 1. [provided by RefSeq, Aug 2013]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with behavioral, ear, and skeletal abnormalities

Clinical highlights

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

GOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.52LOEUF

pLI 0.349

Z-score 2.99

OE 0.23 (0.11–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.62Z-score

OE missense 0.46 (0.40–0.52)

160 obs / 350.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.23 (0.11–0.52)

0≤0.351.4

Missense OE?0.46 (0.40–0.52)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 17.5Missense obs/exp: 160 / 350.7Syn Z: -0.41

Background carrier burden — how many people carry a rare variant somewhere in FEM1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

503 rare PASS variants

Rare truncating (LoF)

1 in 5,800

38 rare PASS variants

Rare synonymous (reference)

1 in 140

299 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FEM1B. 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 220	1 in 8,000
South Asian	~43k	1 in 180	1 in 1,200
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 10,000
European (Finnish)	~27k	1 in 480	1 in 5,300
Admixed American	~22k	1 in 290	none seen
African / African American	~21k	1 in 250	≈ 1 in 9,300
East Asian	~20k	1 in 210	1 in 2,300
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	1 in 320	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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓