FMR1

Chr XXLDX-linked

fragile X messenger ribonucleoprotein 1

Also known as: FMRP, FRAXA, POF, POF1

NCBI Gene: 2332 ENSG00000102081 UniProt: Q06787 OMIM: 309550

FMR1 disease is a repeat disease: what matters is the number of CGG repeats in the gene’s 5′ untranslated region. More than 200 (a full mutation) causes fragile X syndrome; 55–200 (a premutation) carries the risk of fragile X-associated tremor/ataxia syndrome (FXTAS) and primary ovarian insufficiency (FXPOI), and can expand to a full mutation in the next generation; 45–54 is the grey zone.

AGG interruptions inside the repeat make it more stable when passed on. Exome or panel sequencing cannot size the repeat, so testing is by repeat-primed PCR, Southern blot or long-read sequencing.

GeneReviews OMIM ResearchCurated summary · ACMG technical standard 2021, open-access 2025–26 papers

Primary Disease Associations & Inheritance

Fragile X syndromeMIM #300624

XLD

Fragile X tremor/ataxia syndromeMIM #300623

XLD

Premature ovarian failure 1MIM #311360

X-linked

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · fragile X syndrome · XL · ClinGen 2019
Definitive · fragile X-associated tremor/ataxia syndrome · XL · G2P
Definitive · premature ovarian failure 1 · XL · G2P

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

373

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF · n/a

Multiple*

Mechanism· G2P

📖

GeneReview available — FMR1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

FMR1 is a repeat-expansion gene

CGG repeat in the 5′ untranslated region — the cause of fragile X syndrome and the premutation disorders. What matters is the number of repeats.

Normal

Premutation

Full mutation

4555201CGG repeats →

Normal · ≤44
Intermediate · 45–54 — the grey zone
Premutation · 55–200 — FXTAS and FXPOI risk; can expand to a full mutation in the next generation
Full mutation · >200 — fragile X syndrome

AGG interruptions inside the repeat stabilise it and lower the chance of expansion, most clearly below about 70 repeats.

Testing: Exome or panel sequencing cannot size this repeat. Order the dedicated test (repeat-primed PCR with methylation analysis, Southern blot or long-read sequencing); a normal sequencing report does not exclude it.

Sources: ACMG technical standard 2021 (ranges as quoted in open-access papers); AGG: Nolin, Eichler (as cited 2026).