FAM227A

Chr 22

family with sequence similarity 227 member A

The FAM227A protein function is not well characterized, but mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and brain atrophy. Affected children present with early-onset seizures, severe developmental delay, and progressive microcephaly with neuroimaging showing cerebral and cerebellar atrophy.

GOFmechanismLOEUF 1.17
Clinical SummaryFAM227A
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
1.17LOEUF
pLI 0.000
Z-score 0.79
OE 0.85 (0.631.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.10Z-score
OE missense 0.83 (0.750.92)
267 obs / 322.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.85 (0.631.17)
00.351.4
Missense OE0.83 (0.750.92)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 27 / 31.8Missense obs/exp: 267 / 322.6Syn Z: 1.07
DN
0.5869th %ile
GOF
0.6442th %ile
LOF
0.4234th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FAM227A · 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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