NUP35

Chr 2

nucleoporin 35

Also known as: MP-44, MP44, NP44, NUP53

NCBI Gene: 129401 ENSG00000163002 UniProt: Q8NFH5 OMIM: 608140

This gene encodes a member of the nucleoporin family. The encoded protein contains two membrane binding regions, is localized to the nuclear rim, and is part of the nuclear pore complex. All molecules entering or leaving the nucleus either diffuse through or are actively transported by the nuclear pore complex. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 7 and 10. [provided by RefSeq, Dec 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.66

Clinical Summary— NUP35

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 42 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.022

Z-score 2.61

OE 0.34 (0.18–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.89Z-score

OE missense 0.81 (0.71–0.93)

142 obs / 175.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.18–0.66)

0≤0.351.4

Missense OE?0.81 (0.71–0.93)

0≤0.61.4

Synonymous OE?1.47

0≤1.21.6

LoF obs/exp: 6 / 17.9Missense obs/exp: 142 / 175.2Syn Z: -2.83

This gene — mechanism propensity

0.6939th %ile

GOF

0.4579th %ile

LOF

0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS42

Likely Benign1

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	42	0	42
Likely Benign	0	1	1
Benign	0	0	0
Total	42	2	44

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap NUP35 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →