FLYWCH1 encodes a transcription cofactor that negatively regulates gene transcription and participates in DNA damage response signaling. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, seizures, and behavioral abnormalities. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0), indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.35
Clinical SummaryFLYWCH1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.000
Z-score 0.08
OE 0.98 (0.731.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.61Z-score
OE missense 1.35 (1.261.44)
606 obs / 450.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.98 (0.731.35)
00.351.4
Missense OE1.35 (1.261.44)
00.61.4
Synonymous OE1.48
01.21.6
LoF obs/exp: 28 / 28.4Missense obs/exp: 606 / 450.0Syn Z: -5.20

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FLYWCH1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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