FAM124B

Chr 2

family with sequence similarity 124 member B

NCBI Gene: 79843 ENSG00000124019 UniProt: Q9H5Z6 OMIM: 618403

FAM124B encodes a protein that localizes to mitochondria and the nucleoplasm, though its specific function remains unclear. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive brain atrophy. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq

Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.81

OE 0.75 (0.45–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.68Z-score

OE missense 0.88 (0.79–0.98)

221 obs / 251.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.45–1.30)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 9 / 12.1Missense obs/exp: 221 / 251.2Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in FAM124B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 99

619 rare PASS variants

Rare truncating (LoF)

1 in 970

99 rare PASS variants

Rare synonymous (reference)

1 in 260

249 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM124B. 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 170	1 in 930
South Asian	~43k	1 in 100	1 in 970
Remaining (unassigned)	~30k	1 in 89	1 in 1,200
European (Finnish)	~27k	1 in 690	≈ 1 in 6,500
Admixed American	~22k	1 in 110	1 in 440
African / African American	~21k	1 in 76	1 in 1,300
East Asian	~20k	1 in 83	1 in 770
Ashkenazi Jewish	~13k	1 in 1,800	≈ 1 in 5,000
Middle Eastern	~2,884	1 in 86	≈ 1 in 1,400

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 ↓