NUP37

protein-coding

nucleoporin 37, the group of WD repeat domain containing|Nucleoporins

Gene summary

Nuclear pore complexes (NPCs) are used for transporting macromolecules between the cytoplasm and the nucleus. NPCs consist of multiple copies of 30 distinct proteins (nucleoporins), which assemble into biochemically-separable subcomplexes. The protein encoded by this gene is part of a subcomplex (Nup107-160) that is required for proper NPC function as well as for normal kinetochore-microtubule interaction and mitosis. [provided by RefSeq, Dec 2015]

MANE transcript

NM_024057.4

Inheritance

AD, AR

ClinVar variants

P:4U:51B:4

Top phenotype

Microcephaly 24, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr12:102,073,103-102,120,120

External References & Databases

Ensembl (ENSG00000075188)

Transcript & Mutation Effects

hg38 • Region Span ~47.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

microcephaly 24, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032583

Submitter: LiferaOmics

Genetic evidence – Published PMID: 30179222 – Reports three affected brothers from one consanguineous Pakistani family. One proband counted for case-level; additional affected siblings counted under segregation. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = 1.0; Segregation (affected siblings; conservative assignment) = 0.5 Case-control = 0 Family 1 total = 1.5 Published genetic evidence total = 1.5 / 12 Genetic evidence – Our Cases Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = 1.0 Segregation = 0 Case-control = 0 Family 1 total = 1.0 Our Cases Total = 1.0 / 12 Updated Total Genetic Evidence (Published + Our Cases) Published genetic evidence: 1.5 Our additional cases: 1.0 Updated genetic total = 2.5 / 12 Experimental Evidence – Published PMID: 30179222 Evidence supporting biological plausibility: NUP37 is a nuclear pore complex component; patient-derived fibroblasts showed reduced nuclear pore number, altered chromatin organization, abnormal nucleolar morphology, irregular perinuclear spaces, and decreased cellular proliferation, supporting a mechanism relevant to impaired neurodevelopment. Gene function / biological plausibility = 0.5 Functional alteration in patient-derived cells = 1.0 Experimental evidence total = 1.5 / 6 Updated Overall Score Genetic evidence = 2.5 Experimental evidence = 1.5 Updated total = 4.0

microcephaly 24, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032583

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Microcephaly 24, primary, autosomal recessiveAR

Manifestation: Musculoskeletal; 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: 30179222

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUP37 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 46

Microcephaly 24, primary, autosomal recessiveTotal: 6

NUP37-related disorderTotal: 4

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024057.4. 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			46 clinvar	2 clinvar	1 clinvar	49
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	2 clinvar		2 clinvar			4
Total	3	1	51	3	1	59

Highest pathogenic variant AF is 0.000005579769

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024057.4	RefSeq	NP_076962.2	9	MANE Select
ENST00000552283.6	Ensembl	ENSP00000448054.1	9	MANE Select
ENST00000251074.5	Ensembl	ENSP00000251074.1	9	Standard
ENST00000547269.1	Ensembl	ENSP00000447284.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nup37	Danio rerio	Structure: atrium Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

nup37

Danio rerio

Structure: atrium

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
tRNA processing
Disease
Signal Transduction
Gene expression (Transcription)

Biological Process

mRNA export from nucleus
cell cycle
chromosome segregation
viral process
cell division

Molecular Function

protein binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nucleus
nuclear envelope
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000552283
Coding exons: 9
Length: 45936
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.470	152	169	0.898	0.00000822	2138
Missense (PolyPhen)		38	43.703	0.86951		538
Synonymous	1.10	49	59.8	0.820	0.00000321	600
Loss of Function	1.80	11	19.6	0.561	0.00000102	232

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00016	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.00018	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. {ECO:0000269|PubMed:17363900}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.665
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.871

Gene Damage Prediction

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