FAM83A

Chr 8

scaffolding CK1 anchoring protein A

Also known as: BJ-TSA-9, FAM83A

NCBI Gene: 84985 ENSG00000147689 UniProt: Q86UY5

FAM83A encodes a protein that binds to phosphatidylinositol 3-kinase regulatory subunits and protein kinases, and is involved in maintaining mitochondrial function during adipogenesis and epidermal growth factor receptor signaling. Mutations cause amelogenesis imperfecta type IIIA, a disorder of tooth enamel formation, with autosomal dominant inheritance. The gene shows low constraint against loss-of-function variants (LOEUF 1.408), suggesting some tolerance to protein-truncating mutations.

ResearchSummary from RefSeq, OMIM, UniProt

Enables identical protein binding activity; phosphatidylinositol 3-kinase regulatory subunit binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.41

Clinical Summary— FAM83A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

66 VUS of 78 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.41LOEUF

pLI 0.000

Z-score 0.49

OE 0.85 (0.54–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.92 (0.83–1.02)

251 obs / 273.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.85 (0.54–1.41)

0≤0.351.4

Missense OE?0.92 (0.83–1.02)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 11 / 12.9Missense obs/exp: 251 / 273.5Syn Z: 0.87

This gene — mechanism propensity

0.6743th %ile

GOF

0.6442th %ile

LOF

0.4037th %ile

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

DNprediction above median

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

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS66

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	66	66
Likely Benign	4	4
Benign	0	0
Total	70	70

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap FAM83A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →