NUP62

protein-coding

nucleoporin 62, the group of Nucleoporins

Gene summary

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 are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016553.5

Inheritance

AR, AD

ClinVar variants

P:1U:146B:89

Top phenotype

Striatonigral degeneration, infantile

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:49,906,825-49,929,764

External References & Databases

Ensembl (ENSG00000213024)

Transcript & Mutation Effects

hg38 • Region Span ~22.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial infantile bilateral striatal necrosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010080

Submitter: G2P

familial infantile bilateral striatal necrosisMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0010080

Submitter: PanelApp Australia

Leigh syndromeNO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0009723

Submitter: ClinGen

The relationship between NUP62 and Leigh syndrome spectrum (LSS) was evaluated using the ClinGen Clinical Validity Framework as of December 16, 2020. The NUP62 gene encodes nuclear pore glycoprotein p62, a nuclear pore complex component. The nuclear pore complex spans the nuclear envelope and allows the flow of molecules (proteins, RNA, carbohydrates, lipids and signaling molecules) between the nucleus and cytoplasm. The NUP62 gene has been associated with infantile bilateral striatal necrosis. However, after extensive literature review, while the reported cases have brain appearances similar to those observed in LSS, additional evidence of mitochondrial and/or biochemical dysfunction was absent in the reported cases. Additionally, there is no experimental evidence to support this gene-disease relationship. In summary, there is no evidence for a causal role for NUP62 variants in autosomal recessive LSS. This gene-disease association is not supported by experimental evidence and no reports have directly implicated the gene in LSS.

familial infantile bilateral striatal necrosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0010080

Submitter: Ambry Genetics

familial infantile bilateral striatal necrosisLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010080

Submitter: Labcorp Genetics (formerly Invitae)

familial infantile bilateral striatal necrosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010080

Submitter: Orphanet

Clinical Genomic Database (CGD)

Striatonigral degeneration, infantileAR

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: 3729745; 12374138; 14718703; 16786527

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUP62 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 195

not specifiedTotal: 97

NUP62-related disorderTotal: 12

Familial infantile bilateral striatal necrosisTotal: 5

Infantile bilateral striatal necrosisTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016553.5. 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				71 clinvar	6 clinvar	77
missense		1 clinvar	145 clinvar	9 clinvar	3 clinvar	158
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	1	146	80	9	236

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 130 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016553.5	RefSeq	NP_057637.2	1	MANE Select
ENST00000352066.8	Ensembl	ENSP00000305503.3	1	MANE Select
NM_001193357.2	RefSeq	NP_001180286.1	1	Standard
NM_012346.5	RefSeq	NP_036478.2	1	Standard

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)
sumoylation by ranbp2 regulates transcriptional repression

Biological Process

transcription, DNA-templated
mRNA export from nucleus
protein import into nucleus
mitotic metaphase plate congression
centrosome cycle

Molecular Function

chromatin binding
protein binding
phospholipid binding
structural constituent of nuclear pore
kinesin binding

Cellular Component

spindle pole
nucleus
nuclear envelope
annulate lamellae
nuclear pore

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000596217
Coding exons: 1
Length: 22939
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00622	304	304	0.999	0.0000197	3318
Missense (PolyPhen)		49	54.971	0.89138		743
Synonymous	-1.37	164	143	1.15	0.0000113	1194
Loss of Function	2.85	0	9.43	0.00	4.23e-7	116

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex (PubMed:1915414, PubMed:24107630). Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation (PubMed:24107630). It might be involved in protein recruitment to the centrosome after nuclear breakdown (PubMed:24107630). {ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}.;
Disease: DISEASE: Infantile striatonigral degeneration (SNDI) [MIM:271930]: Neurological disorder characterized by symmetrical degeneration of the caudate nucleus, putamen, and occasionally the globus pallidus, with little involvement of the rest of the brain. The clinical features include developmental regression, choreoathetosis, dystonia, spasticity, dysphagia, failure to thrive, nystagmus, optic atrophy, and mental retardation. {ECO:0000269|PubMed:16786527}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: -0.53
RVIS percentile EVS: 20.86

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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