NUFIP1

Chr 13

nuclear FMR1 interacting protein 1

Also known as: NUFIP, Rsa1, bA540M5.1

NCBI Gene: 26747 ENSG00000083635 UniProt: Q9UHK0

This nuclear RNA binding protein interacts with fragile X mental retardation protein (FMRP), regulates RNA polymerase II transcription, and participates in snoRNP biogenesis. Mutations cause autosomal recessive intellectual disability with macrocephaly and seizures, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants in population databases.

ResearchSummary from RefSeq, UniProt

This gene encodes a nuclear RNA binding protein that contains a C2H2 zinc finger motif and a nuclear localization signal. This protein is associated with the nuclear matrix in perichromatin fibrils and, in neurons, localizes to the cytoplasm in association with endoplasmic reticulum ribosomes. This protein interacts with the fragile X mental retardation protein (FMRP), the tumor suppressor protein BRCA1, upregulates RNA polymerase II transcription, and is involved in box C/D snoRNP biogenesis. A pseudogene of this gene resides on chromosome 6q12. [provided by RefSeq, Feb 2012]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Mechanism· predicted

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?

0.97LOEUF

pLI 0.000

Z-score 1.66

OE 0.63 (0.42–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.17Z-score

OE missense 1.03 (0.93–1.14)

268 obs / 260.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.42–0.97)

0≤0.351.4

Missense OE?1.03 (0.93–1.14)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 15 / 23.7Missense obs/exp: 268 / 260.4Syn Z: -1.24

Background carrier burden — how many people carry a rare variant somewhere in NUFIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

623 rare PASS variants

Rare truncating (LoF)

1 in 790

96 rare PASS variants

Rare synonymous (reference)

1 in 200

227 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NUFIP1. 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 120	1 in 740
South Asian	~43k	1 in 99	1 in 520
Remaining (unassigned)	~30k	1 in 93	1 in 2,000
European (Finnish)	~27k	1 in 260	1 in 1,600
Admixed American	~22k	1 in 79	1 in 320
African / African American	~21k	1 in 69	1 in 560
East Asian	~20k	1 in 150	1 in 960
Ashkenazi Jewish	~13k	1 in 690	1 in 1,900
Middle Eastern	~2,884	1 in 110	≈ 1 in 660

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.

Exome coverage (gnomAD): 7 of 10 coding exons well covered in gnomAD exomes; exons 2, 6, 10 marginal. Genomes: all 10.? see exons ↓