NUP54

protein-coding

nucleoporin 54, the group of Nucleoporins

Gene summary

The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the phe-gly (FG) repeat-containing nucleoporin subset. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

MANE transcript

NM_017426.4

Inheritance

ClinVar variants

P:2U:57B:3

Top phenotype

Dystonia 37, early-onset, with striatal lesions

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr4:76,107,562-76,148,485

External References & Databases

Ensembl (ENSG00000138750)

Transcript & Mutation Effects

hg38 • Region Span ~40.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dystonia 37, early-onset, with striatal lesionsMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957385

Submitter: PanelApp Australia

dystonia 37, early-onset, with striatal lesionsLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957385

Submitter: Ambry Genetics

dystonia 37, early-onset, with striatal lesionsLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957385

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Dystonia 37, early-onset, with striatal lesionsAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36333996

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUP54 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 43

Dystonia 37, early-onset, with striatal lesionsTotal: 6

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017426.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	1 clinvar		4
missense	2 clinvar		50 clinvar	2 clinvar		54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	0	57	3	0	62

Highest pathogenic variant AF is 0.000011710613

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017426.4	RefSeq	NP_059122.2	12	MANE Select
ENST00000264883.8	Ensembl	ENSP00000264883.3	12	MANE Select
NM_001278603.2	RefSeq	NP_001265532.1	11	Standard
ENST00000502850.5	Ensembl	ENSP00000426609.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nup54	Danio rerio	Structure: whole organism Quality: wholly ventralized abnormal

Gene / Model

Organism

Observed Phenotype

nup54

Danio rerio

Structure: whole organism

Quality: wholly ventralized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
tRNA processing
Disease
Gene expression (Transcription)
Regulation of HSF1-mediated heat shock response

Biological Process

mRNA export from nucleus
protein targeting
NLS-bearing protein import into nucleus
nuclear pore organization
viral process

Molecular Function

protein binding
structural constituent of nuclear pore

Cellular Component

nuclear envelope
nuclear membrane
nuclear pore central transport channel

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264883
Coding exons: 12
Length: 33857
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	161	258	0.624	0.0000123	3300
Missense (PolyPhen)		25	60.072	0.41617		837
Synonymous	1.41	76	93.3	0.815	0.00000469	987
Loss of Function	3.78	7	29.0	0.242	0.00000157	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00012	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane. {ECO:0000250|UniProtKB:P70582}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.120
RVIS EVS: -0.2
RVIS percentile EVS: 38.82

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.727

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium