FAM219A

Chr 9

family with sequence similarity 219 member A

Also known as: C9orf25

The protein encoded by FAM219A has unknown function, with only basic structural information available from homologous proteins in other species. Mutations in this gene have not been definitively associated with any recognized human disease or neurological disorder. The gene shows moderate tolerance to loss-of-function variants based on population genetic data.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 0.77
Clinical SummaryFAM219A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.146
Z-score 2.07
OE 0.30 (0.130.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.18Z-score
OE missense 0.42 (0.330.54)
47 obs / 111.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.30 (0.130.77)
00.351.4
Missense OE0.42 (0.330.54)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 3 / 10.1Missense obs/exp: 47 / 111.8Syn Z: 0.86
DN
0.7326th %ile
GOF
0.79top 10%
LOF
0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

FAM219A · 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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