NUP88

Chr 17AR

nucleoporin 88

Also known as: FADS4

NCBI Gene: 4927 ENSG00000108559 UniProt: Q99567 OMIM: 602552

The protein is a component of the nuclear pore complex that regulates macromolecular transport between the nucleus and cytoplasm. Mutations cause fetal akinesia deformation sequence 4, an autosomal recessive condition characterized by decreased fetal movement and resulting deformations. The gene shows tolerance to loss-of-function variants (low pLI score), which is consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.691 OMIM phenotype

Clinical Summary— NUP88

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 116 VUS of 173 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

0.69LOEUF

pLI 0.000

Z-score 3.18

OE 0.47 (0.33–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.53Z-score

OE missense 1.07 (0.99–1.16)

436 obs / 406.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.47 (0.33–0.69)

0≤0.351.4

Missense OE?1.07 (0.99–1.16)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 20 / 42.3Missense obs/exp: 436 / 406.2Syn Z: -0.23

ClinVar Variant Classifications

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS116

Likely Benign16

Benign11

Pathogenic

Likely Pathogenic

116

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	2	1	0	4
Likely Pathogenic	1	0	0	0	1
VUS	0	115	0	1	116
Likely Benign	0	9	4	3	16
Benign	0	1	6	4	11
Total	2	127	11	8	148

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap NUP88 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →