NIPAL1

Summary

NIPAL1 (NIPA like domain containing 1, HGNC:27194) is a protein-coding gene on chromosome 4p12, encoding Magnesium transporter NIPA3 (Q6NVV3). Acts as a Mg(2+) transporter.

Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be located in Golgi apparatus. Predicted to be active in membrane.

Source: NCBI Gene 152519 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_207330

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27194
Approved symbol	NIPAL1
Name	NIPA like domain containing 1
Location	4p12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686A06115, SLC57A3, NIPA3
Ensembl gene	ENSG00000163293
Ensembl biotype	protein_coding
OMIM	620340
Entrez	152519

Gene structure

Transcript identifiers

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

ENST00000295461, ENST00000500571, ENST00000508180, ENST00000511123, ENST00000511852, ENST00000513724, ENST00000903458

RefSeq mRNA: 1 — MANE Select: NM_207330 NM_207330

CCDS: CCDS3479

Canonical transcript exons

ENST00000295461 — 6 exons

Exon	Start	End
ENSE00001227197	48035562	48040173
ENSE00001227207	48016772	48016885
ENSE00003598537	48030120	48030176
ENSE00003610566	48025068	48025334
ENSE00003670607	48034881	48035041
ENSE00003683738	48032993	48033083

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 96.92.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3664 / max 44.4481, expressed in 549 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47561	1.2185	526
47562	0.1479	91

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.92	gold quality
upper arm skin	UBERON:0004263	86.48	gold quality
rectum	UBERON:0001052	86.25	gold quality
upper leg skin	UBERON:0004262	85.42	gold quality
oral cavity	UBERON:0000167	85.32	gold quality
esophagus mucosa	UBERON:0002469	84.78	gold quality
lower esophagus mucosa	UBERON:0035834	84.64	gold quality
esophagus squamous epithelium	UBERON:0006920	84.08	gold quality
skin of abdomen	UBERON:0001416	83.84	gold quality
ileal mucosa	UBERON:0000331	83.67	gold quality
zone of skin	UBERON:0000014	83.52	gold quality
skin of leg	UBERON:0001511	83.13	gold quality
colonic mucosa	UBERON:0000317	82.38	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.09	gold quality
skin of hip	UBERON:0001554	79.41	gold quality
jejunal mucosa	UBERON:0000399	77.89	gold quality
mucosa of transverse colon	UBERON:0004991	77.04	gold quality
nipple	UBERON:0002030	75.76	gold quality
liver	UBERON:0002107	75.00	gold quality
islet of Langerhans	UBERON:0000006	74.85	gold quality
mammalian vulva	UBERON:0000997	74.44	gold quality
right lobe of liver	UBERON:0001114	74.32	gold quality
transverse colon	UBERON:0001157	73.77	gold quality
placenta	UBERON:0001987	73.28	gold quality
bone marrow cell	CL:0002092	73.08	gold quality
gingiva	UBERON:0001828	72.85	gold quality
pancreatic ductal cell	CL:0002079	72.39	silver quality
penis	UBERON:0000989	71.24	gold quality
oviduct epithelium	UBERON:0004804	71.20	gold quality
tonsil	UBERON:0002372	71.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.62
E-ENAD-17	no	56.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

167 targeting NIPAL1, 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-450A-1-3P	100.00	69.33	1837
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 3)

• Together with previous reports, our findings support the hypothesis that there could be some relationship between gout and magnesium handling via magnesium transporters including NIPAL1. (PMID:27899376)
• Findings suggest that NIPA like domain containing 1 (NIPAL1) might be a novel factor promoting oral squamous cell carcinoma (OSCC) tumorigenesis, as well as a useful molecular marker of OSCC. (PMID:29464350)
• Genome-wide Association Analysis Across 16,956 Patients Identifies a Novel Genetic Association Between BMP6, NIPAL1, CNGA1 and Spondylosis. (PMID:33332786)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nipal1	ENSMUSG00000067219
rattus_norvegicus	Nipal1	ENSRNOG00000025882
drosophila_melanogaster	spict	FBGN0032451
caenorhabditis_elegans		WBGENE00021820

Paralogs (5): NIPAL3 (ENSG00000001461), NIPAL2 (ENSG00000104361), NIPA2 (ENSG00000140157), NIPA1 (ENSG00000170113), NIPAL4 (ENSG00000172548)

Protein

Protein identifiers

Magnesium transporter NIPA3 — Q6NVV3 (reviewed: Q6NVV3)

Alternative names: NIPA-like protein 1, Non-imprinted in Prader-Willi/Angelman syndrome region protein 3

All UniProt accessions (3): D6RIY2, Q6NVV3, H0Y8W0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Mn(2+), Cu(2+) and Co(2+) but to a much less extent than Mg(2+).

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed in the pancreatic islets.

Similarity. Belongs to the NIPA family.

RefSeq proteins (1): NP_997213* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008521	Mg_trans_NIPA	Family
IPR037185	EmrE-like	Homologous_superfamily

Pfam: PF05653

Catalyzed reactions (Rhea), 1 shown:

• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)

UniProt features (26 total): topological domain 10, transmembrane region 9, glycosylation site 4, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NVV3-F1	80.98	0.46

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 (4): 25, 35, 50, 55

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5223345	Miscellaneous transport and binding events

MSigDB gene sets: 136 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, chr4p12, BILD_HRAS_ONCOGENIC_SIGNATURE, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_TRANSMEMBRANE_TRANSPORT, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, LEE_BMP2_TARGETS_DN, PLASARI_TGFB1_TARGETS_10HR_UP, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_MONOATOMIC_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (3): magnesium ion transport (GO:0015693), monoatomic ion transport (GO:0006811), magnesium ion transmembrane transport (GO:1903830)

GO Molecular Function (1): magnesium ion transmembrane transporter activity (GO:0015095)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	1
transport	1
magnesium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIPAL1	MAGT1	Q9H0U3	757
NIPAL1	CNNM2	Q9H8M5	741
NIPAL1	MMGT1	Q8N4V1	643
NIPAL1	PTP4A2	Q12974	627
NIPAL1	SLC41A1	Q8IVJ1	625
NIPAL1	CNNM3	Q8NE01	593
NIPAL1	TRPM6	Q9BX84	573
NIPAL1	CNNM4	Q6P4Q7	554
NIPAL1	MRS2	Q9HD23	541
NIPAL1	SHLD2	Q86V20	511
NIPAL1	CNNM1	Q9NRU3	494
NIPAL1	SLC41A3	Q96GZ6	476
NIPAL1	SLC41A2	Q96JW4	467
NIPAL1	SLC39A2	Q9NP94	461
NIPAL1	TRPM7	Q96QT4	456
NIPAL1	SLC35H1	Q9NQQ7	456

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640

BioGRID (160): PARP16 (Affinity Capture-MS), PPM1L (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), MCL1 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), TPCN1 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), TMCO3 (Affinity Capture-MS), PM20D2 (Affinity Capture-MS), GOSR2 (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), SEC63 (Affinity Capture-MS), GPRC5C (Affinity Capture-MS)

ESM2 similar proteins: B3LFA3, E7EXX2, F4JKQ7, O23596, P57057, Q0D2K0, Q0D7E4, Q39254, Q3SWX0, Q4KL91, Q4R335, Q5A5P7, Q5KQN0, Q5R7Q3, Q5RD30, Q5RDB8, Q5RKH7, Q5ZHX6, Q6DFC0, Q6K1C4, Q6NVV3, Q6P499, Q6YBV0, Q8BGN5, Q8BMW7, Q8BYR8, Q8CH36, Q8GWX2, Q8GYS1, Q8H184, Q8H4H5, Q8L783, Q8N8Q9, Q8RWF4, Q8RZQ8, Q8VE96, Q91WC7, Q93890, Q93Z81, Q94AH3

Diamond homologs: B3LFA3, F4JKQ7, Q0D2K0, Q3SWX0, Q5A5P7, Q5R7Q3, Q5RDB8, Q6NVV3, Q7RTP0, Q8BHK1, Q8BMW7, Q8BZF2, Q8GWX2, Q8GYS1, Q8N8Q9, Q94AH3, Q9H841, Q9JJC8, Q9LIR9, Q9LNK7, Q91WC7, Q5RD30, Q6P499, Q8BGN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3716 predictions. Top by Δscore:

Variant	Effect	Δscore
4:47940870:C:CC	acceptor_gain	1.0000
4:47942071:A:C	donor_gain	1.0000
4:47943179:A:AC	donor_gain	1.0000
4:47943179:ACT:A	donor_gain	1.0000
4:47943180:C:CC	donor_gain	1.0000
4:47943180:CT:C	donor_gain	1.0000
4:47943180:CTC:C	donor_gain	1.0000
4:47943180:CTCTT:C	donor_gain	1.0000
4:47943285:CTTG:C	acceptor_gain	1.0000
4:47943286:TTG:T	acceptor_gain	1.0000
4:47943287:TG:T	acceptor_gain	1.0000
4:47943289:C:CC	acceptor_gain	1.0000
4:47943365:TCTTA:T	donor_loss	1.0000
4:47943366:CTTA:C	donor_loss	1.0000
4:47943367:TTACC:T	donor_loss	1.0000
4:47943368:TACC:T	donor_loss	1.0000
4:47943370:C:CT	donor_loss	1.0000
4:47943370:CCT:C	donor_gain	1.0000
4:47943413:C:CC	acceptor_gain	1.0000
4:47949824:TATAC:T	donor_loss	1.0000
4:47949825:ATACT:A	donor_loss	1.0000
4:47949826:TACT:T	donor_loss	1.0000
4:47949827:ACTT:A	donor_loss	1.0000
4:47949828:CT:C	donor_loss	1.0000
4:47949829:T:TA	donor_loss	1.0000
4:47949830:TACTG:T	donor_loss	1.0000
4:47949831:A:AC	donor_gain	1.0000
4:47949831:ACT:A	donor_loss	1.0000
4:47949832:C:CA	donor_gain	1.0000
4:47949832:CT:C	donor_gain	1.0000

AlphaMissense

2648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:48025274:A:C	S85R	0.997
4:48025276:C:A	S85R	0.997
4:48025276:C:G	S85R	0.997
4:48025256:A:C	S79R	0.996
4:48025258:T:A	S79R	0.996
4:48025258:T:G	S79R	0.996
4:48033070:A:C	S150R	0.996
4:48033072:T:A	S150R	0.996
4:48033072:T:G	S150R	0.996
4:48035840:T:C	F301L	0.996
4:48035842:T:A	F301L	0.996
4:48035842:T:G	F301L	0.996
4:48034948:A:C	S177R	0.995
4:48034950:T:A	S177R	0.995
4:48034950:T:G	S177R	0.995
4:48030155:T:A	W117R	0.994
4:48030155:T:C	W117R	0.994
4:48033023:C:A	A134D	0.994
4:48033050:T:A	V143D	0.994
4:48034937:G:A	G173D	0.994
4:48034957:G:A	G180R	0.994
4:48034957:G:C	G180R	0.994
4:48034957:G:T	G180W	0.994
4:48034958:G:A	G180E	0.994
4:48035668:T:G	C243W	0.994
4:48035828:G:C	A297P	0.994
4:48035967:G:A	G343E	0.994
4:48033074:T:A	V151D	0.993
4:48033002:G:A	G127E	0.992
4:48035820:T:C	L294P	0.992

dbSNP variants (sampled 300 via entrez): RS1000223851 (4:48035978 A>G), RS1000606258 (4:48031883 C>A,T), RS1000878545 (4:48039271 G>A,C,T), RS1000954809 (4:48024749 C>T), RS1001111703 (4:48033784 CTTTT>C,CTTT), RS1001167497 (4:48025023 C>T), RS1001224261 (4:48033470 A>G), RS1001360676 (4:48017977 C>T), RS1001544107 (4:48031948 A>C), RS1001856443 (4:48018891 A>G), RS1002225624 (4:48032261 T>C), RS1002519229 (4:48022106 G>A), RS1002742748 (4:48015586 T>G), RS1002795458 (4:48015349 G>T), RS1002961628 (4:48029534 T>G)

Disease associations

OMIM: gene MIM:620340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003925_4	Gout	9.000000e-07
GCST003926_3	Renal underexcretion gout	1.000000e-08
GCST006462_15	Uterine fibroids	4.000000e-08
GCST008971_105	Urate levels	4.000000e-08
GCST012020_2	Serum metabolite levels	1.000000e-31
GCST012616_2	Spondylosis	4.000000e-07
GCST90011899_157	Aspartate aminotransferase levels	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC57 NiPA-like magnesium transporter family

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
trichostatin A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Thapsigargin	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4V4	LS180-NIPAL1-KO-c11	Cancer cell line	Female
CVCL_D4V5	LS180-NIPAL1-KO-c3	Cancer cell line	Female

Clinical trials (associated diseases)

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