NXF1

Chr 11

nuclear RNA export factor 1

ENSG00000162231 UniProt: Q9UBU9 OMIM: 602647

This highly constrained gene encodes a nuclear RNA export factor that shuttles between the nucleus and cytoplasm to transport mRNA from the nucleus to the cytoplasm through the TAP/NXF1 pathway. Mutations in NXF1 cause X-linked intellectual disability with or without seizures, typically manifesting in early childhood. The gene follows X-linked inheritance, affecting primarily males with potential carrier effects in females.

OMIM ResearchSummary from RefSeq, UniProt

Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244)

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.976

Z-score 5.03

OE 0.17 (0.09–0.31)

Highly constrained

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

Missense Constraint?

2.66Z-score

OE missense 0.61 (0.55–0.69)

231 obs / 376.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.09–0.31)

0≤0.351.4

Missense OE?0.61 (0.55–0.69)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 7 / 42.4Missense obs/exp: 231 / 376.0Syn Z: 0.66

Background carrier burden — how many people carry a rare variant somewhere in NXF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

692 rare PASS variants

Rare truncating (LoF)

1 in 2,500

89 rare PASS variants

Rare synonymous (reference)

1 in 140

345 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NXF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 2,100
South Asian	~43k	1 in 130	1 in 5,400
Remaining (unassigned)	~30k	1 in 150	1 in 3,300
European (Finnish)	~27k	1 in 170	≈ 1 in 6,700
Admixed American	~22k	1 in 150	≈ 1 in 5,600
African / African American	~21k	1 in 150	1 in 2,500
East Asian	~20k	1 in 200	1 in 1,700
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.