FAM50A

Chr XXLR

family with sequence similarity 50 member A

Also known as: 9F, DXS9928E, HXC-26, HXC26, MRXSA, XAP5

NCBI Gene: 9130ENSG00000071859UniProt: Q14320OMIM: 300453

The protein is involved in regulation of pre-mRNA splicing and likely functions as a DNA-binding protein or transcriptional factor. Mutations cause X-linked syndromic intellectual developmental disorder (Armfield type) through an X-linked recessive inheritance pattern. The high constraint scores (pLI 0.98, LOEUF 0.29) indicate the gene is highly intolerant to loss-of-function variants, suggesting pathogenicity occurs predominantly through haploinsufficiency.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLRLOEUF 0.291 OMIM phenotype
Clinical Summary— FAM50A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 57 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.979
Z-score 3.51
OE 0.06 (0.02–0.29)
Highly constrained

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

Missense Constraint
3.02Z-score
OE missense 0.30 (0.23–0.39)
44 obs / 146.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.29)
0≤0.351.4
Missense OE0.30 (0.23–0.39)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 1 / 16.3Missense obs/exp: 44 / 146.9Syn Z: 0.27
DN
0.4983th %ile
GOF
0.4580th %ile
LOF
0.64top 25%

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

LOFprediction above median · LOEUF 0.29

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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic7
VUS57
Likely Benign14
Benign1
Conflicting1
54
Pathogenic
7
Likely Pathogenic
57
VUS
14
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
5
2
0
7
VUS
2
41
12
2
57
Likely Benign
0
3
5
6
14
Benign
0
0
0
1
1
Conflicting
—1
Total249739134

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM50A · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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