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.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 224 VUS of 308 total submissions

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

308 submitted variants in ClinVar

Classification Summary

Pathogenic35
VUS224
Likely Benign19
Benign4
35
Pathogenic
224
VUS
19
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
208
16
0
224
Likely Benign
0
13
0
6
19
Benign
0
2
0
2
4
Total0223518282

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

View 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC