FAM25C

Chr 10

family with sequence similarity 25 member C

Also known as: bA164N7.4

NCBI Gene: 644054ENSG00000276430UniProt: B3EWG5

I cannot write a clinical gene summary for FAM25C based on the provided information. While constraint scores (pLI: 0.089, LOEUF: 1.898) indicate this gene is not highly constrained against loss-of-function variants, no information about protein function, associated diseases, or inheritance patterns was provided in the data.

Research Assistant →
0
Active trials
0
Pubs (1 yr)
52
P/LP submissions
0%
P/LP missense
1.90
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— FAM25C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 40 VUS of 99 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.90LOEUF
pLI 0.089
Z-score -0.06
OE 1.06 (0.27–1.90)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.03Z-score
OE missense 1.01 (0.74–1.42)
25 obs / 24.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.06 (0.27–1.90)
0≤0.351.4
Missense OE1.01 (0.74–1.42)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 1 / 0.9Missense obs/exp: 25 / 24.6Syn Z: 0.45
DN
0.84top 10%
GOF
0.90top 5%
LOF
0.1796th %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

99 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic18
VUS40
Likely Benign3
Benign3
34
Pathogenic
18
Likely Pathogenic
40
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
18
0
18
VUS
0
20
20
0
40
Likely Benign
0
0
2
1
3
Benign
0
0
3
0
3
Total02077198

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM25C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients