NEMP2

Summary

NEMP2 (nuclear envelope integral membrane protein 2, HGNC:33700) is a protein-coding gene on chromosome 2q32.2, encoding Nuclear envelope integral membrane protein 2 (A6NFY4).

Predicted to be located in nuclear inner membrane. Predicted to be active in nuclear envelope.

Source: NCBI Gene 100131211 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001142645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33700
Approved symbol	NEMP2
Name	nuclear envelope integral membrane protein 2
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189362
Ensembl biotype	protein_coding
OMIM	616497
Entrez	100131211

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 nonsense_mediated_decay, 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000343105, ENST00000409150, ENST00000414176, ENST00000421038, ENST00000444545, ENST00000492292, ENST00000920104

RefSeq mRNA: 1 — MANE Select: NM_001142645 NM_001142645

CCDS: CCDS46476

Canonical transcript exons

ENST00000409150 — 9 exons

Exon	Start	End
ENSE00001577969	190510361	190510537
ENSE00001586718	190534559	190534722
ENSE00001630404	190504338	190509312
ENSE00003464670	190514453	190514678
ENSE00003505680	190518736	190518808
ENSE00003549854	190517520	190517613
ENSE00003551066	190525263	190525378
ENSE00003619096	190518952	190519183
ENSE00003692343	190516270	190516384

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 84.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8931 / max 95.4385, expressed in 1652 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32903	4.9974	1621
32900	0.3052	133
32902	0.2292	103
32901	0.2166	91
32899	0.1448	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.06	gold quality
tendon of biceps brachii	UBERON:0008188	82.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.60	gold quality
ventricular zone	UBERON:0003053	79.72	gold quality
medial globus pallidus	UBERON:0002477	78.08	gold quality
tendon	UBERON:0000043	77.99	gold quality
calcaneal tendon	UBERON:0003701	77.86	gold quality
stromal cell of endometrium	CL:0002255	77.80	gold quality
oocyte	CL:0000023	77.19	silver quality
bone marrow cell	CL:0002092	76.85	gold quality
ganglionic eminence	UBERON:0004023	76.55	gold quality
popliteal artery	UBERON:0002250	76.12	gold quality
tibial artery	UBERON:0007610	76.12	gold quality
adrenal tissue	UBERON:0018303	76.00	gold quality
lymph node	UBERON:0000029	75.89	gold quality
vermiform appendix	UBERON:0001154	75.13	gold quality
globus pallidus	UBERON:0001875	74.25	silver quality
aorta	UBERON:0000947	73.60	gold quality
right coronary artery	UBERON:0001625	73.59	gold quality
leukocyte	CL:0000738	73.42	gold quality
endothelial cell	CL:0000115	73.35	gold quality
left coronary artery	UBERON:0001626	73.07	gold quality
monocyte	CL:0000576	73.04	gold quality
smooth muscle tissue	UBERON:0001135	73.04	gold quality
testis	UBERON:0000473	72.63	gold quality
left testis	UBERON:0004533	72.41	gold quality
coronary artery	UBERON:0001621	72.33	gold quality
secondary oocyte	CL:0000655	72.32	silver quality
descending thoracic aorta	UBERON:0002345	72.01	gold quality
gall bladder	UBERON:0002110	71.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting NEMP2, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3681-3P	99.88	70.46	2254

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nemp2	ENSDARG00000061062
mus_musculus	Nemp2	ENSMUSG00000043015
rattus_norvegicus	Nemp2	ENSRNOG00000012924
drosophila_melanogaster	Nemp	FBGN0030768
caenorhabditis_elegans		WBGENE00017328

Paralogs (1): NEMP1 (ENSG00000166881)

Protein

Protein identifiers

Nuclear envelope integral membrane protein 2 — A6NFY4 (reviewed: A6NFY4)

All UniProt accessions (4): A6NFY4, C9J4F2, F8VWJ7, H7C232

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus inner membrane.

Similarity. Belongs to the NEMP family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NFY4-1	1	yes
A6NFY4-2	2

RefSeq proteins (1): NP_001136117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019358	NEMP_fam	Family

Pfam: PF10225

UniProt features (10 total): transmembrane region 5, splice variant 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NFY4-F1	80.21	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GOCC_NUCLEAR_ENVELOPE, HOWLIN_CITED1_TARGETS_1_UP, GOCC_ORGANELLE_INNER_MEMBRANE, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOCC_NUCLEAR_INNER_MEMBRANE, GOCC_NUCLEAR_MEMBRANE, GOCC_ORGANELLE_ENVELOPE, DLX6_TARGET_GENES, FOXD2_TARGET_GENES, RLF_TARGET_GENES, SFMBT1_TARGET_GENES, SKIL_TARGET_GENES, ZNF282_TARGET_GENES, ZNF407_TARGET_GENES, ZNF618_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleus	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEMP2	ANKAR	Q7Z5J8	661
NEMP2	OSGEPL1	Q9H4B0	541
NEMP2	DIRC1	Q969H9	526
NEMP2	MFSD6	Q6ZSS7	526
NEMP2	HIBCH	Q6NVY1	507
NEMP2	ORMDL1	Q9P0S3	479
NEMP2	PHGR1	C9JFL3	475
NEMP2	BANF1	O75531	435
NEMP2	INPP1	P49441	432
NEMP2	NAB1	Q13506	413
NEMP2	WDR75	Q8IWA0	376
NEMP2	ZMAT1	Q5H9K5	373
NEMP2	AKAP19	P0C876	370
NEMP2	CLEC12B	Q2HXU8	359
NEMP2	MAST3	O60307	348

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): TMEM194B (Affinity Capture-MS), TMEM194B (Affinity Capture-RNA), TMEM194B (Affinity Capture-MS), TMEM194B (Affinity Capture-MS), TMEM194B (Affinity Capture-MS)

ESM2 similar proteins: A6NFY4, A6QNT4, A7MBC7, D3Z291, D3ZEH5, O14524, P0C8N6, P50747, P51811, P60570, Q2HJ63, Q2HJB9, Q3TD49, Q49LS5, Q49LS8, Q5F383, Q5GH61, Q5JZQ8, Q5PQL3, Q5RDB4, Q5RJQ8, Q5XII8, Q5ZJY9, Q5ZKY0, Q60GF7, Q6AXN4, Q6AYS5, Q6ZQE4, Q7SYC7, Q80UF9, Q811Q0, Q8C561, Q8CB65, Q8CHQ0, Q8CIF6, Q8K2I9, Q8NFZ0, Q8TCT8, Q8VEC4, Q90YH8

Diamond homologs: A1L3G9, A6NFY4, A7MBC7, B9X187, E7FE40, F1QYC4, O14524, P0C8N6, Q19293, Q28EH9, Q5RDB4, Q5ZJY9, Q6ZQE4, Q8CB65, Q9VXD6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1544 predictions. Top by Δscore:

Variant	Effect	Δscore
2:190509152:T:TA	donor_gain	1.0000
2:190510359:A:AC	donor_gain	1.0000
2:190510360:C:CC	donor_gain	1.0000
2:190518814:G:GC	acceptor_gain	1.0000
2:190518945:GACTT:G	donor_loss	1.0000
2:190518946:ACTTA:A	donor_loss	1.0000
2:190518948:TTA:T	donor_loss	1.0000
2:190518949:TACTG:T	donor_loss	1.0000
2:190518950:A:AC	donor_gain	1.0000
2:190518950:A:C	donor_loss	1.0000
2:190518951:C:CA	donor_gain	1.0000
2:190518951:C:T	donor_loss	1.0000
2:190518951:CT:C	donor_gain	1.0000
2:190518951:CTG:C	donor_gain	1.0000
2:190518951:CTGTT:C	donor_gain	1.0000
2:190509153:C:A	donor_gain	0.9900
2:190510354:GACTT:G	donor_loss	0.9900
2:190510355:ACTT:A	donor_loss	0.9900
2:190510356:CTTA:C	donor_loss	0.9900
2:190510357:TTA:T	donor_loss	0.9900
2:190510358:TA:T	donor_loss	0.9900
2:190510359:ACT:A	donor_loss	0.9900
2:190510360:C:G	donor_loss	0.9900
2:190510360:CTTG:C	donor_gain	0.9900
2:190514452:CCA:C	donor_gain	0.9900
2:190514633:T:C	acceptor_gain	0.9900
2:190517611:CTT:C	acceptor_gain	0.9900
2:190517614:C:CC	acceptor_gain	0.9900
2:190518734:A:AC	donor_gain	0.9900
2:190518735:C:CT	donor_gain	0.9900

AlphaMissense

2727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:190514650:G:C	S252R	0.992
2:190514650:G:T	S252R	0.992
2:190514652:T:G	S252R	0.992
2:190509300:A:C	F381L	0.984
2:190509300:A:T	F381L	0.984
2:190509302:A:G	F381L	0.984
2:190510395:A:G	W366R	0.976
2:190510395:A:T	W366R	0.976
2:190516354:A:G	C215R	0.972
2:190525277:A:G	W67R	0.969
2:190525277:A:T	W67R	0.969
2:190509301:A:G	F381S	0.966
2:190509298:A:T	V382D	0.965
2:190510430:A:G	L354P	0.965
2:190509301:A:C	F381C	0.962
2:190516351:A:G	W216R	0.962
2:190516351:A:T	W216R	0.962
2:190510393:C:A	W366C	0.956
2:190510393:C:G	W366C	0.956
2:190514661:C:G	G249R	0.955
2:190514661:C:T	G249R	0.955
2:190510427:C:G	R355P	0.954
2:190509310:A:G	F378S	0.953
2:190519169:A:C	S76R	0.949
2:190519169:A:T	S76R	0.949
2:190519171:T:G	S76R	0.949
2:190517576:C:G	G186R	0.948
2:190516373:A:C	F208L	0.947
2:190516373:A:T	F208L	0.947
2:190516375:A:G	F208L	0.947

dbSNP variants (sampled 300 via entrez): RS1000018158 (2:190499584 C>G), RS1000023906 (2:190546697 T>A), RS1000026890 (2:190460331 T>A), RS1000058512 (2:190517930 A>C), RS1000067459 (2:190647508 CTT>C), RS1000078690 (2:190460536 T>C), RS1000088689 (2:190499208 A>G), RS1000091584 (2:190586391 C>G), RS1000092279 (2:190492028 C>A,G,T), RS1000093194 (2:190647805 C>T), RS1000093869 (2:190552232 A>T), RS1000146913 (2:190426559 T>C), RS1000163178 (2:190500635 G>A), RS1000166944 (2:190486775 AT>A), RS1000170866 (2:190506636 T>C)

Disease associations

OMIM: gene MIM:616497 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST003518_14	Daytime sleep phenotypes	3.000000e-06
GCST004280_83	Diastolic blood pressure	1.000000e-11
GCST007094_193	Diastolic blood pressure	2.000000e-06
GCST007095_1	Systolic blood pressure	9.000000e-06
GCST007095_94	Systolic blood pressure	3.000000e-07
GCST007096_38	Pulse pressure	1.000000e-10
GCST007097_55	Pulse pressure	3.000000e-06
GCST007097_56	Pulse pressure	1.000000e-06
GCST007099_203	Systolic blood pressure	5.000000e-13
GCST011096_35	Systemic lupus erythematosus	1.000000e-13
GCST011097_1	Systemic lupus erythematosus	7.000000e-09
GCST90011866_10	Systemic lupus erythematosus	3.000000e-06
GCST90014033_20	Haemorrhoidal disease	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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