NPIPA5

Summary

NPIPA5 (nuclear pore complex interacting protein family member A5, HGNC:41980) is a protein-coding gene on chromosome 16p13.11, encoding Nuclear pore complex-interacting protein family member A5 (E9PKD4).

At a glance

• Clinical variants (ClinVar): 9 total — 2 pathogenic
• MANE Select transcript: NM_001277325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:41980
Approved symbol	NPIPA5
Name	nuclear pore complex interacting protein family member A5
Location	16p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183793
Ensembl biotype	protein_coding
Entrez	100288332

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000360151, ENST00000534094, ENST00000543801

RefSeq mRNA: 2 — MANE Select: NM_001277325 NM_001277325, NM_001351200

CCDS: CCDS59264, CCDS86506

Canonical transcript exons

ENST00000360151 — 8 exons

Exon	Start	End
ENSE00002140663	15365429	15365464
ENSE00002145121	15365574	15365634
ENSE00002152756	15370020	15370119
ENSE00002154441	15373715	15373843
ENSE00002157002	15366653	15366760
ENSE00002176057	15363628	15364069
ENSE00002182767	15378232	15378294
ENSE00003502055	15369712	15369856

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.65.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	97.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.77	gold quality
cerebellar cortex	UBERON:0002129	96.59	gold quality
cerebellum	UBERON:0002037	96.54	gold quality
cerebellar hemisphere	UBERON:0002245	96.50	gold quality
superior frontal gyrus	UBERON:0002661	94.45	gold quality
mucosa of stomach	UBERON:0001199	93.87	gold quality
anterior cingulate cortex	UBERON:0009835	92.44	gold quality
right frontal lobe	UBERON:0002810	91.91	gold quality
lower esophagus mucosa	UBERON:0035834	91.69	gold quality
left testis	UBERON:0004533	91.52	gold quality
Ammon’s horn	UBERON:0001954	91.43	gold quality
hypothalamus	UBERON:0001898	91.39	gold quality
right testis	UBERON:0004534	91.28	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.28	gold quality
amygdala	UBERON:0001876	91.26	gold quality
pituitary gland	UBERON:0000007	90.95	gold quality
apex of heart	UBERON:0002098	90.82	gold quality
temporal lobe	UBERON:0001871	90.77	gold quality
testis	UBERON:0000473	90.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.62	gold quality
left ovary	UBERON:0002119	89.50	gold quality
substantia nigra	UBERON:0002038	89.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.23	gold quality
putamen	UBERON:0001874	89.15	gold quality
metanephros cortex	UBERON:0010533	89.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.03	gold quality
adenohypophysis	UBERON:0002196	88.82	gold quality
caudate nucleus	UBERON:0001873	88.70	gold quality
nucleus accumbens	UBERON:0001882	88.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.71

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (19): NPIPB12 (ENSG00000169203), NPIPB3 (ENSG00000169246), NPIPA1 (ENSG00000183426), NPIPA6 (ENSG00000183889), NPIPB4 (ENSG00000185864), NPIPB15 (ENSG00000196436), NPIPB9 (ENSG00000196993), NPIPB13 (ENSG00000198064), NPIPB6 (ENSG00000198156), NPIPA8 (ENSG00000214940), NPIPA7 (ENSG00000214967), NPIPA3 (ENSG00000224712), NPIPA9 (ENSG00000233024), NPIPB7 (ENSG00000233232), NPIPB2 (ENSG00000234719), NPIPB5 (ENSG00000243716), NPIPB11 (ENSG00000254206), NPIPA2 (ENSG00000254852), NPIPB8 (ENSG00000255524)

Protein

Protein identifiers

Nuclear pore complex-interacting protein family member A5 — E9PKD4 (reviewed: E9PKD4)

All UniProt accessions (2): E9PJ88, E9PKD4

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the NPIP family.

Isoforms (2)

UniProt ID	Names	Canonical?
E9PKD4-1	1	yes
E9PKD4-2	2

RefSeq proteins (2): NP_001264254, NP_001338129 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009443	NPIP	Family
IPR054697	NPIP_N	Domain

Pfam: PF06409

UniProt features (4 total): splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E9PKD4-F1	52.14	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 3 (showing top): ZHONG_PFC_C3_ASTROCYTE, HE_LIM_SUN_FETAL_LUNG_C1_GHRL_POS_NE_PRECURSOR_CELL, chr16p13

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

849 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPIPA5	GOLGA6B	A6NDN3	507
NPIPA5	PDXDC1	Q6P996	479
NPIPA5	LRRC37A3	O60309	447
NPIPA5	NUP62	P37198	439
NPIPA5	MPV17L	Q2QL34	419
NPIPA5	H3BMD7	H3BMD7	400
NPIPA5	CEP20	Q96NB1	395
NPIPA5	LRRC37A	A6NMS7	391
NPIPA5	AGAP6	Q5VW22	377
NPIPA5	NBPF4	Q96M43	360
NPIPA5	NASP	P49321	355
NPIPA5	LENG1	Q96BZ8	352
NPIPA5	MARF1	Q9Y4F3	339
NPIPA5	TRIM51	Q9BSJ1	321
NPIPA5	GARIN4	Q8IYT1	317

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0B4J1W7, A0A7H0DN35, A4QN01, A6NHN6, A6NJ64, A8MQ11, E9PIF3, E9PJ23, E9PJI5, E9PKD4, E9PQR5, F5HGC2, F8W1W9, F8WFD2, O75200, O83374, P05913, P06486, P07396, P0C7Q2, P0CK47, P0CK48, P0DM63, P0DXC3, P15489, P16765, P16802, P20969, P36443, P38900, P47003, P68341, P68454, P68455, P87191, P92537, P92561, Q03418, Q32M92, Q4ZGE2

Diamond homologs: A0A0B4J1W7, A6NHN6, A6NJ64, A6NJU9, A8MRT5, C9JG80, E5RHQ5, E9PIF3, E9PJ23, E9PJI5, E9PKD4, E9PQR5, F8W0I5, F8W1W9, F8WFD2, O75200, P0DM63, P0DXC3, Q92617, Q9UND3, O70490, Q08AH1, Q08AH3, Q3UNX5, Q53FZ2, Q5REV5, Q68CK6, Q6AYT9, Q6NUN0, Q6SKG1, Q8BGA8, Q8K0L3, Q91VA0, Q9BEA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	3
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
625566	GRCh37/hg19 16p13.11(chr16:14975292-16301530)	Pathogenic
625597	GRCh37/hg19 16p13.11(chr16:15129970-16284116)	Pathogenic

SpliceAI

986 predictions. Top by Δscore:

Variant	Effect	Δscore
16:15365572:A:AC	donor_gain	1.0000
16:15365573:C:CC	donor_gain	1.0000
16:15366651:A:AC	donor_gain	1.0000
16:15366652:C:CC	donor_gain	1.0000
16:15366757:CAGA:C	acceptor_gain	1.0000
16:15366761:C:CC	acceptor_gain	1.0000
16:15369710:A:AC	donor_gain	1.0000
16:15369711:C:CA	donor_gain	1.0000
16:15369711:CTGTT:C	donor_gain	1.0000
16:15369728:T:TA	donor_gain	1.0000
16:15370018:ACCTT:A	donor_gain	1.0000
16:15370019:CCTTC:C	donor_gain	1.0000
16:15370022:T:A	donor_gain	1.0000
16:15370044:T:TA	donor_gain	1.0000
16:15370117:CAC:C	acceptor_gain	1.0000
16:15370118:ACC:A	acceptor_loss	1.0000
16:15370119:CCTA:C	acceptor_loss	1.0000
16:15370120:CTA:C	acceptor_loss	1.0000
16:15370121:T:C	acceptor_loss	1.0000
16:15373706:TATAC:T	donor_loss	1.0000
16:15373708:TACT:T	donor_loss	1.0000
16:15373709:AC:A	donor_loss	1.0000
16:15373710:C:CG	donor_loss	1.0000
16:15373711:T:TA	donor_loss	1.0000
16:15373713:A:AC	donor_gain	1.0000
16:15373713:A:AT	donor_loss	1.0000
16:15373714:C:CG	donor_gain	1.0000
16:15373714:CA:C	donor_gain	1.0000
16:15373714:CACA:C	donor_gain	1.0000
16:15373714:CACAA:C	donor_gain	1.0000

AlphaMissense

2278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:15365625:A:C	F185L	0.965
16:15365625:A:T	F185L	0.965
16:15365627:A:G	F185L	0.965
16:15373799:A:C	F36L	0.928
16:15373799:A:T	F36L	0.928
16:15373801:A:G	F36L	0.928
16:15369828:A:C	F107L	0.914
16:15369828:A:T	F107L	0.914
16:15369830:A:G	F107L	0.914
16:15373763:A:C	F48L	0.909
16:15373763:A:T	F48L	0.909
16:15373765:A:G	F48L	0.909
16:15370111:G:C	F67L	0.897
16:15370111:G:T	F67L	0.897
16:15370113:A:G	F67L	0.897
16:15365463:A:G	I203T	0.875
16:15366665:A:G	I178T	0.874
16:15365574:T:A	K202N	0.861
16:15365574:T:G	K202N	0.861
16:15364061:C:A	M217I	0.855
16:15364061:C:G	M217I	0.855
16:15364061:C:T	M217I	0.855
16:15365626:A:G	F185S	0.835
16:15370105:C:A	K69N	0.832
16:15370105:C:G	K69N	0.832
16:15373786:A:G	W41R	0.829
16:15373786:A:T	W41R	0.829
16:15365463:A:C	I203S	0.826
16:15366699:C:G	A167P	0.823
16:15369729:C:A	R140S	0.822

dbSNP variants (sampled 300 via entrez): RS1000286020 (16:15383376 C>T), RS1000550905 (16:15369972 C>A), RS1000876498 (16:15382139 C>T), RS1000929824 (16:15376117 A>G), RS1001052689 (16:15368782 C>A,G), RS1001137791 (16:15368513 T>A), RS1001350440 (16:15376392 G>A), RS1001818587 (16:15380671 T>C), RS1001870822 (16:15381085 C>A,T), RS1001956183 (16:15374914 G>A), RS1002089246 (16:15367272 G>C), RS1002387650 (16:15374440 C>T), RS1002877306 (16:15379958 AAT>A,AATAT), RS1002982724 (16:15372006 C>T), RS1003061256 (16:15364254 G>C,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:157900

GenCC curated gene-disease

Mondo (1): Mobius syndrome (MONDO:0008006)

Orphanet (1): Moebius syndrome (Orphanet:570)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mivebresib	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	decreases expression	1
(+)-JQ1 compound	increases expression	1
Cadmium	decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies