FAM120A

Chr 9

family with sequence similarity 120 member A

Also known as: C9orf10, HBVPTPAP, OSSA

This protein functions as an RNA-binding scaffolding protein that regulates oxidative stress survival signaling, enables SRC family kinase activation of PI3-kinase, and promotes IGF2 protein production by binding IGF2 RNA. Mutations cause autosomal dominant developmental delay with facial dysmorphism and dental anomalies, typically presenting in early childhood. The gene is highly constrained against loss-of-function variation in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.16
Clinical SummaryFAM120A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
80 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.99
OE 0.06 (0.030.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.35Z-score
OE missense 0.63 (0.580.68)
410 obs / 650.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.030.16)
00.351.4
Missense OE0.63 (0.580.68)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 3 / 47.6Missense obs/exp: 410 / 650.3Syn Z: 0.75
DN
0.2798th %ile
GOF
0.3491th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.16

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

100 submitted variants in ClinVar

Classification Summary

VUS80
Likely Benign3
80
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
79
0
0
80
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total1810183

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM120A · 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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