NIPA1

Summary

NIPA1 (NIPA magnesium transporter 1, HGNC:17043) is a protein-coding gene on chromosome 15q11.2, encoding Magnesium transporter NIPA1 (Q7RTP0). Acts as a Mg(2+) transporter.

This gene encodes a magnesium transporter that associates with early endosomes and the cell surface in a variety of neuronal and epithelial cells. This protein may play a role in nervous system development and maintenance. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with autosomal dominant spastic paraplegia 6.

Source: NCBI Gene 123606 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia 6 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 327 total — 3 pathogenic
• Phenotypes (HPO): 57
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_144599

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17043
Approved symbol	NIPA1
Name	NIPA magnesium transporter 1
Location	15q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC35570, SLC57A1
Ensembl gene	ENSG00000170113
Ensembl biotype	protein_coding
OMIM	608145
Entrez	123606

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000337435, ENST00000437912, ENST00000557930, ENST00000559448, ENST00000560069, ENST00000560105, ENST00000561183, ENST00000905597, ENST00000941787

RefSeq mRNA: 2 — MANE Select: NM_144599 NM_001142275, NM_144599

CCDS: CCDS73691, CCDS73692

Canonical transcript exons

ENST00000337435 — 5 exons

Exon	Start	End
ENSE00001363170	22823728	22829789
ENSE00001369730	22786644	22786834
ENSE00003472173	22810749	22810796
ENSE00003523818	22820313	22820473
ENSE00003660935	22812163	22812253

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 97.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5676 / max 190.5001, expressed in 1623 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145450	5.1676	1585
145451	1.3109	572
145449	0.0891	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	97.00	gold quality
globus pallidus	UBERON:0001875	96.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.14	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.98	gold quality
spinal cord	UBERON:0002240	94.84	gold quality
postcentral gyrus	UBERON:0002581	94.79	gold quality
subthalamic nucleus	UBERON:0001906	94.76	gold quality
inferior vagus X ganglion	UBERON:0005363	94.24	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.21	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.13	gold quality
substantia nigra pars compacta	UBERON:0001965	93.85	gold quality
parietal lobe	UBERON:0001872	93.45	gold quality
lateral globus pallidus	UBERON:0002476	93.44	gold quality
substantia nigra	UBERON:0002038	93.31	gold quality
pons	UBERON:0000988	93.27	gold quality
midbrain	UBERON:0001891	93.01	gold quality
superior frontal gyrus	UBERON:0002661	92.77	gold quality
middle temporal gyrus	UBERON:0002771	92.58	gold quality
medulla oblongata	UBERON:0001896	92.44	gold quality
superior vestibular nucleus	UBERON:0007227	91.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.29	gold quality
corpus callosum	UBERON:0002336	91.18	gold quality
Ammon’s horn	UBERON:0001954	91.06	gold quality
entorhinal cortex	UBERON:0002728	90.75	gold quality
putamen	UBERON:0001874	89.82	gold quality
prefrontal cortex	UBERON:0000451	89.80	gold quality
primary visual cortex	UBERON:0002436	89.74	gold quality
temporal lobe	UBERON:0001871	89.62	gold quality
occipital lobe	UBERON:0002021	89.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

191 targeting NIPA1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• located in the genomic domain between break points 1 and 2 on chromosome 15, of the Prader-Willi/Angelman syndromes (PMID:14508708)
• discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant hereditary spastic paraplegia (PMID:14508710)
• novel missense substitution in a highly conserved NIPA1 residue (G106R) which further confirms a causative link between NIPA1 mutation and autosomal dominant hereditary spastic paraplegia (PMID:15711826)
• quantitated mRNA levels of NIPA2, NIPA2,l CYFIP1, and GCP5 in Prader-Willi syndrome and correlated levels with psychological and behavior scales (PMID:16982806)
• NIPA1 normally encodes a Mg2+ transporter and the loss-of function of NIPA1(SPG6) due to abnormal trafficking of the mutated protein provides the basis of the hereditary spastic paraplegia phenotype (PMID:17166836)
• Amino acid substitution mutations implicated in a family with autosomal dominant spastic paraplegia. (PMID:17205300)
• utations in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia and further demonstrates genotype-phenotype correlations in SPG6 (PMID:17928003)
• We propose that Hereditary spastic paraplegia-associated mutations in NIPA1 lead to cellular and functional deficits through a gain-of-function mechanism supporting the endoplasmic reticulum accumulation of toxic NIPA1 proteins. (PMID:19091982)
• The hereditary spastic paraplegia proteins NIPA1, spastin and spartin inhibit BMP signalling by promoting BMP receptors degradation. (PMID:19620182)
• a genome-wide association study of amyotrophic lateral sclerosis identified the NIPA1 locus as a candidate for more in-depth studies (PMID:20685689)
• One heterozygous missense mutation of NIPA1 was identified in a complicated form of hereditary spastic paraplegia type 6 family with peripheral nerves disease (PMID:21419568)
• Epilepsy might be more common in spastic paraplegia type 6 than in other forms of Hereditary spastic paraplegia because of a genetic risk factor closely linked to NIPA1. (PMID:21599812)
• NIPA1 polyalanine repeat expansions are a common risk factor for ALS and modulate disease course (PMID:22378146)
• study reports direct evidence of de novo c.316G>A mutation in the same hotspot of the gene in two unrelated patients who had otherwise a prototypical NIPA1-associated phenotype with a severe form of uncomplicated spastic paraplegia (PMID:24075313)
• We report here a family with a pure form of Hereditary spastic paraplegia due to a de novo transition mutation in the NIPA1 gene. (PMID:25133278)
• NIPA1 repeat expansion in the context of a C9orf72 repeat expansion would drive toward a motor neuron disease phenotype. (PMID:26777436)
• This study showed that the mutations of were detected in SPG11, ATL1, NIPA1, and ABCD1 in patient with hereditary spastic paraplegia. (PMID:27084228)
• we employed an shRNA-encoding lentivirus system to inhibit SPG6 expression in AML cells including NB4 and MV4-11cells. Knockdown expression of SPG6 resulted in decreased cell growth and elevated apoptosis of these leukemia cells. Notably, SPG6 deficiency resulted in higher BMPR2 expression indicating that BMPR2 signaling contributes to AML pathogenesis. (PMID:29715457)
• There is an evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS. (PMID:30342764)
• No role of NIPA1 repeat length as a modifier of the C9orf72 ALS disease risk. (PMID:31286297)
• Clinical and genetic characterization of NIPA1 mutations in a Taiwanese cohort with hereditary spastic paraplegia. (PMID:36607129)
• LncRNA NIPA1-SO confers atherosclerotic protection by suppressing the transmembrane protein NIPA1. (PMID:36736696)
• Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy. (PMID:38667292)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nipa1	ENSDARG00000055917
mus_musculus	Nipa1	ENSMUSG00000047037
rattus_norvegicus	Nipa1	ENSRNOG00000042702

Paralogs (5): NIPAL3 (ENSG00000001461), NIPAL2 (ENSG00000104361), NIPA2 (ENSG00000140157), NIPAL1 (ENSG00000163293), NIPAL4 (ENSG00000172548)

Protein

Protein identifiers

Magnesium transporter NIPA1 — Q7RTP0 (reviewed: Q7RTP0)

Alternative names: Non-imprinted in Prader-Willi/Angelman syndrome region protein 1, Spastic paraplegia 6 protein

All UniProt accessions (3): Q7RTP0, H0YLP7, H0YMY7

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+), Zn(2+) and Co(2+) but to a much less extent than Mg(2+).

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Early endosome.

Tissue specificity. Widely expressed with highest levels in neuronal tissues.

Disease relevance. Spastic paraplegia 6, autosomal dominant (SPG6) [MIM:600363] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NIPA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7RTP0-1	1	yes
Q7RTP0-2	2

RefSeq proteins (2): NP_001135747, NP_653200* (*=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 (23 total): topological domain 10, transmembrane region 9, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTP0-F1	86.00	0.66

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 267 (showing top): GGGACCA_MIR133A_MIR133B, GCM_PTPRD, TGCACTT_MIR519C_MIR519B_MIR519A, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MAGNESIUM_ION_TRANSPORT, chr15q11, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, BILD_E2F3_ONCOGENIC_SIGNATURE, GCM_MAPK10, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_UP, TTTGCAC_MIR19A_MIR19B, GOBP_TRANSMEMBRANE_TRANSPORT, GCM_PTK2, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (4): magnesium ion transport (GO:0015693), transmembrane transport (GO:0055085), monoatomic ion transport (GO:0006811), magnesium ion transmembrane transport (GO:1903830)

GO Molecular Function (2): magnesium ion transmembrane transporter activity (GO:0015095), protein binding (GO:0005515)

GO Cellular Component (4): early endosome (GO:0005769), plasma membrane (GO:0005886), membrane (GO:0016020), endosome (GO:0005768)

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
transport	2
metal ion transport	1
cellular process	1
magnesium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
binding	1
endosome	1
membrane	1
cell periphery	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIPA1	TUBGCP5	Q96RT8	983
NIPA1	CYFIP1	Q7L576	965
NIPA1	SPAST	Q9UBP0	933
NIPA1	IGFBP2	P18065	905
NIPA1	REEP1	Q9H902	901
NIPA1	SPART	Q8N0X7	893
NIPA1	WASHC5	Q12768	870
NIPA1	ATL1	Q8WXF7	861
NIPA1	KIF5A	Q12840	792
NIPA1	ZFYVE27	Q5T4F4	769
NIPA1	SPG21	Q9NZD8	766
NIPA1	BMPR2	Q13873	757
NIPA1	SPG7	Q9UQ90	646
NIPA1	SPG11	Q96JI7	643
NIPA1	RTN2	O75298	619

IntAct

17 interactions, top by confidence:

A	B	Type	Score
NIPA1	CCDC167	psi-mi:“MI:0915”(physical association)	0.560
NIPA1	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
NIPA1	TOM1L1	psi-mi:“MI:0915”(physical association)	0.400
NIPA1	SMO	psi-mi:“MI:0915”(physical association)	0.370
NIPA1	CREB3	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
NIPA1	UNC119B	psi-mi:“MI:0914”(association)	0.350
NIPA2	ELP6	psi-mi:“MI:0914”(association)	0.350
SELENOM	NIPA1	psi-mi:“MI:0915”(physical association)	0.000
CCDC167	NIPA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (183): SELM (Two-hybrid), CCDC167 (Two-hybrid), NIPA1 (Affinity Capture-MS), NIPA1 (Affinity Capture-MS), NIPA1 (Proximity Label-MS), NIPA1 (Proximity Label-MS), NIPA1 (Two-hybrid), NIPA1 (Affinity Capture-RNA), TOM1L1 (Affinity Capture-MS), NIPA1 (Affinity Capture-MS), NIPA1 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ADAM15 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), GPR64 (Affinity Capture-MS)

ESM2 similar proteins: A0NGI1, A7YW81, O74750, O94654, P40004, Q00974, Q02334, Q03730, Q04083, Q09875, Q0D2K0, Q0V9U2, Q10000, Q29Q28, Q3E6T0, Q3SWX0, Q54V96, Q54ZG7, Q550W6, Q55FV8, Q5R7Q3, Q5T1Q4, Q6CR04, Q6FSF8, Q7RTP0, Q7TML3, Q8BGK5, Q8BHK1, Q8BLX4, Q8BMW7, Q8BZF2, Q8IXU6, Q8MXJ9, Q8N8Q9, Q8R1E7, Q8WY98, Q94EI9, Q968A5, Q9C8M1, Q9JJC8

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	166
Likely benign	78
Benign	59

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2521	NM_144599.5(NIPA1):c.316G>C (p.Gly106Arg)	Pathogenic
2523	NM_144599.5(NIPA1):c.316G>A (p.Gly106Arg)	Pathogenic
948417	NM_144599.5(NIPA1):c.731A>G (p.Gln244Arg)	Pathogenic

SpliceAI

1418 predictions. Top by Δscore:

Variant	Effect	Δscore
15:22786833:C:A	donor_loss	1.0000
15:22786836:CTAC:C	donor_loss	1.0000
15:22786837:CCTA:C	donor_loss	1.0000
15:22810795:C:CC	donor_gain	1.0000
15:22810796:A:AC	donor_gain	1.0000
15:22819378:C:CC	donor_gain	1.0000
15:22819379:A:AC	donor_gain	1.0000
15:22820305:T:TC	acceptor_gain	1.0000
15:22820310:C:G	acceptor_loss	1.0000
15:22820311:CC:C	acceptor_loss	1.0000
15:22820311:CCTT:C	acceptor_gain	1.0000
15:22820315:TGGAC:T	acceptor_gain	1.0000
15:22820473:A:AT	donor_loss	1.0000
15:22820474:TA:T	donor_loss	1.0000
15:22820476:ATTAC:A	donor_loss	1.0000
15:22823724:T:C	acceptor_loss	1.0000
15:22823725:C:CC	acceptor_gain	1.0000
15:22823725:C:CG	acceptor_loss	1.0000
15:22823726:AC:A	acceptor_loss	1.0000
15:22823727:CA:C	acceptor_gain	1.0000
15:22823728:ACAC:A	acceptor_loss	1.0000
15:22823729:AACA:A	acceptor_gain	1.0000
15:22823730:AAACA:A	acceptor_gain	1.0000
15:22786833:CCTCG:C	donor_gain	0.9900
15:22794319:T:TA	donor_gain	0.9900
15:22810795:CTTG:C	donor_gain	0.9900
15:22819374:T:C	donor_gain	0.9900
15:22819375:A:AC	donor_gain	0.9900
15:22819375:ATGT:A	donor_gain	0.9900
15:22819378:CT:C	donor_gain	0.9900

AlphaMissense

2106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:22824012:T:C	F255L	0.999
15:22824014:C:A	F255L	0.999
15:22824014:C:G	F255L	0.999
15:22824051:T:C	F268L	0.999
15:22824053:T:A	F268L	0.999
15:22824053:T:G	F268L	0.999
15:22820368:G:T	G125W	0.998
15:22820389:G:C	G132R	0.998
15:22820390:G:A	G132D	0.998
15:22823967:A:C	S240R	0.998
15:22823969:C:A	S240R	0.998
15:22823969:C:G	S240R	0.998
15:22786771:A:C	S39R	0.997
15:22786773:C:A	S39R	0.997
15:22786773:C:G	S39R	0.997
15:22786784:G:A	G43E	0.997
15:22786810:G:C	G52R	0.997
15:22820368:G:A	G125R	0.997
15:22820368:G:C	G125R	0.997
15:22820369:G:A	G125E	0.997
15:22820383:T:C	C130R	0.997
15:22823834:C:G	C195W	0.997
15:22823847:A:C	S200R	0.997
15:22823849:T:A	S200R	0.997
15:22823849:T:G	S200R	0.997
15:22824139:G:A	G297E	0.997
15:22824159:G:A	G304R	0.997
15:22824159:G:C	G304R	0.997
15:22824159:G:T	G304W	0.997
15:22824160:G:A	G304E	0.997

dbSNP variants (sampled 300 via entrez): RS1000061107 (15:22825151 C>G), RS1000070978 (15:22825382 A>C), RS1000112263 (15:22787204 C>G,T), RS1000168351 (15:22788169 G>A,C), RS1000182012 (15:22785489 A>G), RS1000210274 (15:22808651 T>C), RS1000291664 (15:22827057 C>G), RS1000292924 (15:22815068 C>A,G), RS1000309819 (15:22803179 A>G), RS1000322387 (15:22827252 G>A), RS1000359941 (15:22803382 C>A,G,T), RS1000449428 (15:22800301 C>G,T), RS1000470411 (15:22796667 G>A), RS1000479400 (15:22786569 T>C,G), RS1000547745 (15:22787363 G>T)

Disease associations

OMIM: gene MIM:608145 | disease phenotypes: MIM:600363, MIM:303350, MIM:189800

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 6	Strong	Autosomal dominant

Mondo (3): hereditary spastic paraplegia 6 (MONDO:0010878), hereditary spastic paraplegia (MONDO:0019064), preeclampsia (MONDO:0005081)

Orphanet (3): Autosomal dominant spastic paraplegia type 6 (Orphanet:100988), Hereditary spastic paraplegia (Orphanet:685), Preeclampsia (Orphanet:275555)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000174	Abnormal palate morphology
HP:0000252	Microcephaly
HP:0000337	Broad forehead
HP:0000377	Abnormal pinna morphology
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001680	Coarctation of aorta
HP:0001761	Pes cavus
HP:0001999	Abnormal facial shape
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008162_45	Hip circumference	5.000000e-06
GCST009615_16	Triglyceride levels x loop diuretics use interaction	4.000000e-07
GCST009615_17	Triglyceride levels x loop diuretics use interaction	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C536866	Spastic paraplegia 6, autosomal dominant (supp.)

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

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
TL8-506	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression, increases methylation	1
potassium perchlorate	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	increases abundance, increases expression	1
aflatoxin B2	decreases methylation	1
diallyl trisulfide	increases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Leflunomide	increases expression	1
Atrazine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Poly I-C	affects cotreatment, increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Vanadates	decreases expression	1
Zinc	increases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KB	N/Tert-1 NIPA1	Telomerase immortalized cell line	Male
CVCL_D4H0	HCT116-NIPA1-KO-c16	Cancer cell line	Male
CVCL_D4H1	HCT116-NIPA1-KO-c22	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia