FAM50A

Chr XXLR

family with sequence similarity 50 member A

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

NCBI Gene: 9130 ENSG00000071859 UniProt: Q14320 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene belongs to the FAM50 family. The encoded protein is highly conserved in length and sequence across different species. It is a basic protein containing a nuclear localization signal, and may function as a DNA-binding protein or a transcriptional factor. [provided by RefSeq, Sep 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLRLOEUF 0.291 OMIM phenotype

Clinical Summary— FAM50A

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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.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 46 VUS of 131 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 OE?0.06 (0.02–0.29)

0≤0.351.4

Missense OE?0.30 (0.23–0.39)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 1 / 16.3Missense obs/exp: 44 / 146.9Syn Z: 0.27

This gene — mechanism propensity

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

131 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic5

VUS46

Likely Benign14

Benign1

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	5	0	0	5
VUS	2	41	1	2	46
Likely Benign	0	3	5	6	14
Benign	0	0	0	1	1
Conflicting	—				1
Total	2	49	6	9	67

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

View in ClinVar →

59 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap FAM50A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →