FAM124A

Chr 13

family with sequence similarity 124 member A

NCBI Gene: 220108 ENSG00000150510 UniProt: Q86V42

This gene encodes a protein that functions in cellular stress response and protein quality control pathways. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability, seizures, and movement disorders typically presenting in infancy. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

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?

1.43LOEUF

pLI 0.000

Z-score 0.25

OE 0.93 (0.62–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.99Z-score

OE missense 0.85 (0.77–0.94)

292 obs / 343.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.93 (0.62–1.43)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 15 / 16.1Missense obs/exp: 292 / 343.8Syn Z: 1.30

Background carrier burden — how many people carry a rare variant somewhere in FAM124A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

751 rare PASS variants

Rare truncating (LoF)

1 in 730

110 rare PASS variants

Rare synonymous (reference)

1 in 150

321 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM124A. 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 72	1 in 950
South Asian	~43k	1 in 62	1 in 400
Remaining (unassigned)	~30k	1 in 55	1 in 990
European (Finnish)	~27k	1 in 320	1 in 1,300
Admixed American	~22k	1 in 63	1 in 1,100
African / African American	~21k	1 in 46	1 in 690
East Asian	~20k	1 in 140	1 in 880
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 9,900
Middle Eastern	~2,884	1 in 70	≈ 1 in 950

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓