FAM222A

Chr 12

family with sequence similarity 222 member A

Also known as: C12orf34

FAM222A encodes a protein of unknown function that is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.45). Biallelic mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and brain malformations.

LOFmechanismLOEUF 0.45
Clinical SummaryFAM222A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.851
Z-score 2.74
OE 0.09 (0.030.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.12Z-score
OE missense 0.82 (0.740.91)
246 obs / 300.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.030.45)
00.351.4
Missense OE0.82 (0.740.91)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 1 / 10.6Missense obs/exp: 246 / 300.8Syn Z: 0.94
DN
0.3693th %ile
GOF
0.4283th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.45

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FAM222A · 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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