NUP210L

Summary

NUP210L (nucleoporin 210 like, HGNC:29915) is a protein-coding gene on chromosome 1q21.3, encoding Nuclear pore membrane glycoprotein 210-like (Q5VU65).

Predicted to act upstream of or within Sertoli cell development and spermatid development. Predicted to be located in membrane. Predicted to be part of nuclear pore.

Source: NCBI Gene 91181 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 212 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_207308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29915
Approved symbol	NUP210L
Name	nucleoporin 210 like
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143552
Ensembl biotype	protein_coding
OMIM	621033
Entrez	91181

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000271854, ENST00000368553, ENST00000368559

RefSeq mRNA: 2 — MANE Select: NM_207308 NM_001159484, NM_207308

CCDS: CCDS41399, CCDS53370

Canonical transcript exons

ENST00000368559 — 40 exons

Exon	Start	End
ENSE00000960818	153995076	153995180
ENSE00000960819	153993015	153993089
ENSE00001072787	154054770	154054832
ENSE00001072788	154025542	154025716
ENSE00001072789	154027506	154027597
ENSE00001072790	154022126	154022343
ENSE00001072792	154009972	154010121
ENSE00001072794	154054228	154054407
ENSE00001072795	154023122	154023297
ENSE00001072797	154018933	154019069
ENSE00001072800	154046289	154046369
ENSE00001072801	154029896	154030054
ENSE00001072805	154012244	154012370
ENSE00001072807	154046069	154046200
ENSE00001215132	154000856	154001060
ENSE00001215136	154001735	154001985
ENSE00001447403	153992690	153992935
ENSE00001594689	154129277	154129345
ENSE00001610257	154141431	154141524
ENSE00001630793	154127311	154127417
ENSE00001641769	154089421	154089594
ENSE00001658760	154118671	154118808
ENSE00001660713	154117725	154117880
ENSE00001666258	154139802	154139952
ENSE00001671898	154056815	154056947
ENSE00001673104	154060540	154060641
ENSE00001673980	154143446	154143577
ENSE00001675062	154070273	154070465
ENSE00001682718	154126323	154126463
ENSE00001683816	154152736	154152872
ENSE00001692471	154061586	154061674
ENSE00001704289	154104012	154104210
ENSE00001725360	154138106	154138238
ENSE00001736824	154060942	154061046
ENSE00001749391	154099998	154100143
ENSE00001755421	154135814	154135972
ENSE00001775412	154094935	154095156
ENSE00001785724	154058089	154058216
ENSE00001797458	154058565	154058693
ENSE00002224107	154154842	154155073

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 85.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1590 / max 87.9616, expressed in 31 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14773	0.1590	31

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	85.11	gold quality
left testis	UBERON:0004533	83.59	gold quality
right testis	UBERON:0004534	83.17	gold quality
testis	UBERON:0000473	81.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.03	gold quality
adult organism	UBERON:0007023	71.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.15	gold quality
buccal mucosa cell	CL:0002336	67.05	gold quality
calcaneal tendon	UBERON:0003701	58.32	gold quality
granulocyte	CL:0000094	58.18	gold quality
tibialis anterior	UBERON:0001385	57.32	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.70	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
bone marrow cell	CL:0002092	53.22	gold quality
deltoid	UBERON:0001476	52.94	gold quality
colonic epithelium	UBERON:0000397	52.86	gold quality
cortical plate	UBERON:0005343	52.66	gold quality
pancreatic ductal cell	CL:0002079	52.20	silver quality
corpus callosum	UBERON:0002336	51.79	gold quality
tendon	UBERON:0000043	51.43	gold quality
cerebellar cortex	UBERON:0002129	50.57	gold quality
cerebellar hemisphere	UBERON:0002245	50.49	gold quality
myocardium	UBERON:0002349	50.25	gold quality
cerebellum	UBERON:0002037	49.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	48.78	gold quality
muscle tissue	UBERON:0002385	47.82	gold quality
ileal mucosa	UBERON:0000331	47.31	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NUP210L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-12116	97.94	68.91	595
HSA-MIR-3131	95.33	65.74	102
HSA-MIR-611	93.79	64.24	81
HSA-MIR-3655	86.11	61.77	117

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nup210l	ENSMUSG00000027939
rattus_norvegicus	Nup210l	ENSRNOG00000055790
drosophila_melanogaster	Gp210	FBGN0266580
caenorhabditis_elegans	npp-12	WBGENE00003798

Paralogs (1): NUP210 (ENSG00000132182)

Protein

Protein identifiers

Nuclear pore membrane glycoprotein 210-like — Q5VU65 (reviewed: Q5VU65)

Alternative names: Nucleoporin 210 kDa-like, Nucleoporin Nup210-like

All UniProt accessions (2): Q5VU65, X6R6V8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus membrane.

Disease relevance. Spermatogenic failure 97 (SPGF97) [MIM:621057] An autosomal recessive, male infertility disorder characterized by oligoasthenoteratozoospermia. Infertile subjects have low sperm count, poor motility and highly abnormal spermatozoa with strikingly large heads due to highly uncondensed nuclear sperm DNA. The disease may be caused by variants affecting the gene represented in this entry. In a patient with spermatogenic failure, a homozygous loss-of-function variant affecting a splice site in the NUP210L gene has been identified. However, NUP210L knockout male mice show only mild anomalies of sperm head morphology and decreased motility and are fertile. Re-examination of the patient allowed the identification of an additional variant in the NUP153 gene (p.Pro485Leu). It has been proposed that the increased phenotypic severity associated with NUP210L loss in the patient was due to the presence of this additional variant. Although interspecies divergence in the nuclear pore function of NUP210L cannot be ruled out.

Similarity. Belongs to the NUP210 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VU65-1	1	yes
Q5VU65-2	2

RefSeq proteins (2): NP_001152956, NP_997191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003343	Big_2	Domain
IPR008964	Invasin/intimin_cell_adhesion	Homologous_superfamily
IPR045197	NUP210-like	Family
IPR055094	NUP210_Ig15	Domain
IPR055095	NUP210_Ig_C	Domain
IPR055096	Ig_NUP210_1st	Domain
IPR055097	Ig_NUP210_2nd	Domain
IPR055098	Ig_NUP210_3rd	Domain
IPR055099	Ig_NUP210_7th	Domain
IPR056897	Ig_NUP210_4th	Domain
IPR056898	Ig_NUP210_6th	Domain
IPR056899	Ig_NUP210_9th	Domain
IPR057586	Ig_NUP210_16th	Domain
IPR058779	Ig_NUP210_13th	Domain

Pfam: PF02368, PF22957, PF22959, PF22962, PF22963, PF22967, PF22969, PF24902, PF24935, PF24991, PF25354, PF26181, PF26182, PF26183, PF26184

UniProt features (23 total): glycosylation site 9, sequence conflict 8, signal peptide 1, chain 1, splice variant 1, sequence variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VU65-F1	79.54	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (9): 931, 1445, 1859, 84, 304, 348, 495, 522, 812

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOZGIT_ESR1_TARGETS_DN, GOBP_SERTOLI_CELL_DEVELOPMENT, GOBP_MALE_GAMETE_GENERATION, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SEX_DIFFERENTIATION, RYTTCCTG_ETS2_B, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, HAND1E47_01, GOBP_SERTOLI_CELL_DIFFERENTIATION, HOXA4_Q2, GOBP_MALE_SEX_DIFFERENTIATION

GO Biological Process (2): spermatid development (GO:0007286), Sertoli cell development (GO:0060009)

GO Molecular Function (0):

GO Cellular Component (4): nuclear pore (GO:0005643), nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear envelope	2
germ cell development	1
spermatid differentiation	1
epithelial cell development	1
developmental process involved in reproduction	1
Sertoli cell differentiation	1
nuclear protein-containing complex	1
nucleus	1
organelle membrane	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP210L	C1orf185	Q5T7R7	511
NUP210L	C9orf153	Q5TBE3	505
NUP210L	NUP35	Q8NFH5	503
NUP210L	NUP62CL	Q9H1M0	498
NUP210L	SPATS1	Q496A3	449
NUP210L	ZNF578	Q96N58	447
NUP210L	NUP85	Q9BW27	442
NUP210L	NUP155	O75694	439
NUP210L	TMCO5A	Q8N6Q1	438
NUP210L	NUP205	Q92621	437
NUP210L	NUP54	Q7Z3B4	423
NUP210L	NUP107	P57740	422
NUP210L	DRC5	Q5JU00	419
NUP210L	SPDYC	Q5MJ68	419
NUP210L	BTBD18	B2RXH4	414

IntAct

1 interactions, top by confidence:

A	B	Type	Score
NXT2	MYO1G	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): NUP210L (Co-fractionation), NUP210L (Affinity Capture-MS), NUP210L (Affinity Capture-MS), NUP210L (Affinity Capture-MS), NUP210L (Affinity Capture-RNA)

ESM2 similar proteins: A0A8M2B818, A2VDJ0, B0S5G3, B5X561, D3YXG0, F1LW30, F1QVU0, F4K4R6, F4KHD8, O46634, O95256, P0CI71, P14719, P27931, P42702, P43303, Q00651, Q01638, Q3SXY7, Q3U095, Q504C1, Q5NDE6, Q5NDE7, Q5R482, Q5RFR6, Q5VU65, Q5XNR9, Q6B3P0, Q6B457, Q6GMZ9, Q6P2S7, Q6UXZ4, Q86UP6, Q8CBC6, Q8IZA0, Q8K1S2, Q8L7F9, Q8N2E2, Q8VDA1, Q8WY21

Diamond homologs: P11654, Q5VU65, Q8TEM1, Q9D2F7, Q9QY81

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

212 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	178
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3393508	NUP210L, IVS5, G-A, -1	Pathogenic
4849366	NM_207308.3(NUP210L):c.674del (p.Gly225fs)	Likely pathogenic

SpliceAI

7421 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153995193:C:CT	acceptor_gain	1.0000
1:154009967:CTTA:C	donor_loss	1.0000
1:154009968:TTAC:T	donor_loss	1.0000
1:154009969:TA:T	donor_loss	1.0000
1:154009970:A:AT	donor_loss	1.0000
1:154009971:CCTTT:C	donor_gain	1.0000
1:154018929:TTA:T	donor_loss	1.0000
1:154018930:TA:T	donor_loss	1.0000
1:154018931:ACC:A	donor_loss	1.0000
1:154018932:CC:C	donor_loss	1.0000
1:154018932:CCT:C	donor_gain	1.0000
1:154018955:C:CA	donor_gain	1.0000
1:154019066:TCAC:T	acceptor_gain	1.0000
1:154019067:CAC:C	acceptor_gain	1.0000
1:154019067:CACC:C	acceptor_gain	1.0000
1:154019069:CCT:C	acceptor_loss	1.0000
1:154019070:C:CC	acceptor_gain	1.0000
1:154019070:CTAGG:C	acceptor_loss	1.0000
1:154019071:T:A	acceptor_loss	1.0000
1:154022123:TACC:T	donor_loss	1.0000
1:154022124:A:AC	donor_gain	1.0000
1:154022124:AC:A	donor_gain	1.0000
1:154022125:C:CC	donor_gain	1.0000
1:154022125:CC:C	donor_gain	1.0000
1:154022125:CCATG:C	donor_gain	1.0000
1:154022339:CATCT:C	acceptor_gain	1.0000
1:154022341:TCT:T	acceptor_gain	1.0000
1:154022342:CT:C	acceptor_gain	1.0000
1:154022342:CTC:C	acceptor_gain	1.0000
1:154022343:TCT:T	acceptor_gain	1.0000

AlphaMissense

12389 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154141486:A:G	W171R	0.998
1:154141486:A:T	W171R	0.998
1:154117853:A:G	W498R	0.996
1:154117853:A:T	W498R	0.996
1:154152872:C:A	W68C	0.995
1:154152872:C:G	W68C	0.995
1:154054827:A:C	F1082L	0.994
1:154054827:A:T	F1082L	0.994
1:154054829:A:G	F1082L	0.994
1:154141484:C:A	W171C	0.993
1:154141484:C:G	W171C	0.993
1:154141514:A:C	F161L	0.992
1:154141514:A:T	F161L	0.992
1:154141516:A:G	F161L	0.992
1:154001907:A:T	V1670D	0.991
1:154070369:A:G	W820R	0.991
1:154070369:A:T	W820R	0.991
1:154154843:A:G	W68R	0.991
1:154154843:A:T	W68R	0.991
1:154117851:C:A	W498C	0.990
1:154117851:C:G	W498C	0.990
1:154046119:A:G	W1216R	0.989
1:154046119:A:T	W1216R	0.989
1:154117765:G:T	A527D	0.989
1:154001974:A:G	C1648R	0.988
1:154143472:A:G	L149P	0.988
1:154010056:A:G	C1616R	0.987
1:154138142:A:C	Y272D	0.987
1:154141511:A:C	S162R	0.987
1:154141511:A:T	S162R	0.987

dbSNP variants (sampled 300 via entrez): RS1000040094 (1:154090028 G>A), RS1000079794 (1:154141909 C>A,T), RS1000102785 (1:154108145 G>C), RS1000112073 (1:154010705 T>C), RS1000116325 (1:154003328 C>T), RS1000117765 (1:154049892 G>A), RS1000127958 (1:154035812 C>T), RS1000169786 (1:154008801 G>A), RS1000176923 (1:154147413 C>T), RS1000216284 (1:154102483 G>A), RS1000231395 (1:154003593 C>A), RS1000248638 (1:154102788 T>C,G), RS1000249357 (1:153993913 GAC>G), RS1000279170 (1:154053568 T>A,C), RS1000286503 (1:154046802 C>T)

Disease associations

OMIM: gene MIM:621033 | disease phenotypes: MIM:127400, MIM:615010, MIM:621057

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure	Limited	Autosomal recessive

Mondo (4): dyschromatosis symmetrica hereditaria (MONDO:0007483), Aicardi-Goutieres syndrome 6 (MONDO:0014007), spermatogenic failure 97 (MONDO:0975958), spermatogenic failure (MONDO:0004983)

Orphanet (2): Dyschromatosis symmetrica hereditaria (Orphanet:41), Aicardi-Goutières syndrome (Orphanet:51)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012208	Immotile sperm
HP:0025437	Macrozoospermia
HP:0032558	Absent sperm flagella
HP:0034818	Severe oligozoospermia
HP:0045058	Abnormality of the testis size
HP:6000135	Low semen volume

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004599_249	Mean platelet volume	5.000000e-09
GCST004616_113	Platelet distribution width	5.000000e-14
GCST006019_20	Gamma glutamyl transferase levels	2.000000e-10
GCST010136_18	Fruit consumption	3.000000e-08
GCST010137_3	Cooked vegetable consumption	3.000000e-09
GCST010142_60	Fish- and plant-related diet	4.000000e-09
GCST010142_92	Fish- and plant-related diet	6.000000e-14
GCST010696_22	Cortical thickness (min-P)	4.000000e-10
GCST010697_50	Cortical surface area (min-P)	1.000000e-12
GCST010698_81	Subcortical volume (min-P)	1.000000e-23
GCST010699_7	Brain morphology (min-P)	1.000000e-10
GCST010700_11	Cortical thickness (MOSTest)	4.000000e-13
GCST010701_73	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_45	Subcortical volume (MOSTest)	4.000000e-10
GCST010703_276	Brain morphology (MOSTest)	2.000000e-15
GCST012216_2	Vegetable consumption	1.000000e-08
GCST90002395_530	Mean platelet volume	1.000000e-17
GCST90002396_142	Mean reticulocyte volume	4.000000e-13
GCST90002400_522	Plateletcrit	4.000000e-11
GCST90002401_360	Platelet distribution width	1.000000e-31
GCST90002402_492	Platelet count	2.000000e-20

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535729	Dyschromatosis symmetrica hereditaria 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	3
aristolochic acid I	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Cadmium	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Folic Acid	decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06309407	Not specified	COMPLETED	Dosimeter Location in Pain Physicians