FAM124B

Chr 2

family with sequence similarity 124 member B

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.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
29
P/LP submissions
0%
P/LP missense
1.30
LOEUF
Mechanism
Clinical SummaryFAM124B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 63 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.30LOEUF
pLI 0.000
Z-score 0.81
OE 0.75 (0.451.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.68Z-score
OE missense 0.88 (0.790.98)
221 obs / 251.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.451.30)
00.351.4
Missense OE0.88 (0.790.98)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 9 / 12.1Missense obs/exp: 221 / 251.2Syn Z: 0.53

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic1
VUS63
Likely Benign7
28
Pathogenic
1
Likely Pathogenic
63
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
1
0
1
VUS
0
61
2
0
63
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total06731199

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM124B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC