NIPAL2

Summary

NIPAL2 (NIPA like domain containing 2, HGNC:25854) is a protein-coding gene on chromosome 8q22.2, encoding NIPA-like protein 2 (Q9H841).

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

Source: NCBI Gene 79815 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001321635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25854
Approved symbol	NIPAL2
Name	NIPA like domain containing 2
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13955, SLC57A4
Ensembl gene	ENSG00000104361
Ensembl biotype	protein_coding
Entrez	79815

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000341166, ENST00000430223, ENST00000519324, ENST00000520545, ENST00000520735, ENST00000521820, ENST00000521949, ENST00000522188, ENST00000852806, ENST00000852807, ENST00000852808

RefSeq mRNA: 3 — MANE Select: NM_001321635 NM_001321635, NM_001321636, NM_024759

CCDS: CCDS6278, CCDS83310

Canonical transcript exons

ENST00000430223 — 11 exons

Exon	Start	End
ENSE00002110763	98294003	98294235
ENSE00003486014	98254019	98254087
ENSE00003490567	98194728	98194822
ENSE00003511074	98203108	98203196
ENSE00003511700	98205111	98205246
ENSE00003548568	98236155	98236214
ENSE00003594860	98189826	98193090
ENSE00003611065	98212405	98212501
ENSE00003637822	98222479	98222600
ENSE00003641221	98252463	98252634
ENSE00003684345	98195942	98196005

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0283 / max 82.3464, expressed in 1515 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94086	3.3417	1253
94087	0.8934	576
94089	0.7083	426
94090	0.3189	173
94088	0.3188	158
94083	0.1271	62
94093	0.1111	50
94092	0.0979	49
94091	0.0690	31
94084	0.0300	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.99	gold quality
upper leg skin	UBERON:0004262	97.58	gold quality
nasal cavity epithelium	UBERON:0005384	96.95	gold quality
skin of hip	UBERON:0001554	96.85	gold quality
parotid gland	UBERON:0001831	96.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.00	gold quality
middle temporal gyrus	UBERON:0002771	95.46	gold quality
ileal mucosa	UBERON:0000331	95.44	gold quality
pancreatic ductal cell	CL:0002079	95.16	gold quality
rectum	UBERON:0001052	94.93	gold quality
mammalian vulva	UBERON:0000997	94.84	gold quality
gingiva	UBERON:0001828	94.83	gold quality
gingival epithelium	UBERON:0001949	94.81	gold quality
left ovary	UBERON:0002119	94.52	gold quality
skin of abdomen	UBERON:0001416	93.86	gold quality
zone of skin	UBERON:0000014	93.76	gold quality
right ovary	UBERON:0002118	93.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.70	gold quality
endothelial cell	CL:0000115	93.56	gold quality
skin of leg	UBERON:0001511	93.53	gold quality
colonic mucosa	UBERON:0000317	93.28	gold quality
corpus epididymis	UBERON:0004359	93.12	gold quality
esophagus mucosa	UBERON:0002469	92.81	gold quality
primary visual cortex	UBERON:0002436	92.62	gold quality
penis	UBERON:0000989	92.46	gold quality
palpebral conjunctiva	UBERON:0001812	92.35	gold quality
epithelial cell of pancreas	CL:0000083	92.34	silver quality
lower esophagus mucosa	UBERON:0035834	92.25	gold quality
oral cavity	UBERON:0000167	92.21	gold quality
endocervix	UBERON:0000458	92.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting NIPAL2, 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-12118	100.00	65.88	1270
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30E-3P	99.87	69.68	2942

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nipal2	ENSMUSG00000038879
rattus_norvegicus	Nipal2	ENSRNOG00000005190

Paralogs (5): NIPAL3 (ENSG00000001461), NIPA2 (ENSG00000140157), NIPAL1 (ENSG00000163293), NIPA1 (ENSG00000170113), NIPAL4 (ENSG00000172548)

Protein

Protein identifiers

NIPA-like protein 2 — Q9H841 (reviewed: Q9H841)

All UniProt accessions (1): Q9H841

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the NIPA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H841-2	1	yes
Q9H841-1	2

RefSeq proteins (3): NP_001308564, NP_001308565, NP_079035 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008521	Mg_trans_NIPA	Family
IPR037185	EmrE-like	Homologous_superfamily

Pfam: PF05653

UniProt features (16 total): transmembrane region 9, glycosylation site 3, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H841-F1	79.86	0.54

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 (3): 23, 33, 274

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 107 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, RYTTCCTG_ETS2_B, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, USF_02, NERF_Q2, GOBP_TRANSMEMBRANE_TRANSPORT, MGGAAGTG_GABP_B, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (2): magnesium ion transport (GO:0015693), magnesium ion transmembrane transport (GO:1903830)

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

GO Cellular Component (1): 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
magnesium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
cellular anatomical structure	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIPAL2	MAGT1	Q9H0U3	755
NIPAL2	PTP4A2	Q12974	635
NIPAL2	SLC41A1	Q8IVJ1	624
NIPAL2	CNNM2	Q9H8M5	605
NIPAL2	CNNM3	Q8NE01	595
NIPAL2	CCDC90B	Q9GZT6	566
NIPAL2	CNNM4	Q6P4Q7	557
NIPAL2	TRPM6	Q9BX84	540
NIPAL2	CNNM1	Q9NRU3	495
NIPAL2	WDR74	Q6RFH5	490
NIPAL2	TXNDC16	Q9P2K2	476
NIPAL2	MRS2	Q9HD23	476
NIPAL2	IQGAP3	Q86VI3	474
NIPAL2	VPS13B	Q7Z7G8	454
NIPAL2	MMGT1	Q8N4V1	451

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NIPAL2	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
MFSD6	EIF3CL	psi-mi:“MI:0914”(association)	0.350
NIPAL2	ATP5MC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): NIPAL2 (Two-hybrid), NIPAL2 (Affinity Capture-RNA), NIPAL2 (Affinity Capture-MS), ATP5G3 (Affinity Capture-MS), ATR (Affinity Capture-MS)

ESM2 similar proteins: A1L272, A2RV80, A4IF30, A6QL92, A6QPI1, O02777, O80605, P17200, P20272, P21554, P47746, P51810, P56971, P70259, Q1LZI2, Q2V4F9, Q3TDN0, Q3UGM2, Q4R794, Q5F383, Q5FVJ3, Q5IS73, Q5R4D7, Q5R6J3, Q5RD30, Q66H88, Q6P0E8, Q6P499, Q6R5J2, Q71SP5, Q8BGN5, Q8BZK4, Q8CBH5, Q8IY50, Q8NA31, Q8NBV4, Q8R314, Q8RWF4, Q8WV83, Q91WB2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1869 predictions. Top by Δscore:

Variant	Effect	Δscore
8:98193434:A:C	acceptor_gain	1.0000
8:98252630:TATTT:T	acceptor_gain	1.0000
8:98252632:TTT:T	acceptor_gain	1.0000
8:98252634:TCTGA:T	acceptor_loss	1.0000
8:98252636:T:C	acceptor_loss	1.0000
8:98252647:C:CT	acceptor_gain	1.0000
8:98254013:TCTTA:T	donor_loss	1.0000
8:98254014:CTTA:C	donor_loss	1.0000
8:98254015:TTA:T	donor_loss	1.0000
8:98254016:TACC:T	donor_loss	1.0000
8:98254017:ACCT:A	donor_loss	1.0000
8:98254018:C:CG	donor_loss	1.0000
8:98254086:ATCTG:A	acceptor_loss	1.0000
8:98254087:TCTG:T	acceptor_loss	1.0000
8:98254088:C:CC	acceptor_gain	1.0000
8:98254088:C:T	acceptor_loss	1.0000
8:98254089:T:A	acceptor_loss	1.0000
8:98293997:CCTTA:C	donor_loss	1.0000
8:98293998:CTTA:C	donor_loss	1.0000
8:98293999:TTAC:T	donor_loss	1.0000
8:98294000:TA:T	donor_loss	1.0000
8:98193430:A:AC	acceptor_gain	0.9900
8:98193433:CA:C	acceptor_gain	0.9900
8:98193434:A:AC	acceptor_gain	0.9900
8:98194803:C:CT	acceptor_gain	0.9900
8:98194804:A:T	acceptor_gain	0.9900
8:98205109:A:AC	donor_gain	0.9900
8:98205110:C:CC	donor_gain	0.9900
8:98205110:CTTGA:C	donor_gain	0.9900
8:98205242:TGAGG:T	acceptor_gain	0.9900

AlphaMissense

2477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:98254037:A:C	S62R	0.990
8:98254037:A:T	S62R	0.990
8:98254039:T:G	S62R	0.990
8:98195942:C:T	G315E	0.975
8:98203121:A:C	S289R	0.969
8:98203121:A:T	S289R	0.969
8:98203123:T:G	S289R	0.969
8:98222557:A:C	F160L	0.962
8:98222557:A:T	F160L	0.962
8:98222559:A:G	F160L	0.962
8:98195943:C:G	G315R	0.957
8:98195943:C:T	G315R	0.957
8:98222579:C:T	G153E	0.955
8:98194821:A:G	C316R	0.953
8:98195943:C:A	G315W	0.951
8:98222580:C:G	G153R	0.950
8:98222580:C:T	G153R	0.950
8:98252519:G:T	A107D	0.950
8:98194802:C:T	G322D	0.949
8:98254054:C:G	G57R	0.945
8:98254054:C:T	G57R	0.945
8:98194803:C:G	G322R	0.943
8:98222600:C:T	G146D	0.938
8:98203108:C:G	G294R	0.936
8:98254049:G:C	N58K	0.931
8:98254049:G:T	N58K	0.931
8:98205220:C:G	A228P	0.930
8:98252507:G:T	A111D	0.930
8:98236155:C:G	G146R	0.928
8:98254074:C:T	G50E	0.925

dbSNP variants (sampled 300 via entrez): RS1000022314 (8:98211773 T>G), RS1000029250 (8:98276352 C>A,T), RS1000035041 (8:98230366 T>C), RS1000106651 (8:98230015 G>A), RS1000120924 (8:98222118 C>G), RS1000162314 (8:98217922 G>T), RS1000194726 (8:98239481 C>T), RS1000200521 (8:98287569 T>C), RS1000201092 (8:98234013 A>G), RS1000212769 (8:98217418 C>G,T), RS1000225419 (8:98274081 G>A), RS1000288881 (8:98194945 A>C,G), RS1000291763 (8:98254734 C>G,T), RS1000303107 (8:98201706 A>G), RS1000330239 (8:98236550 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001859_45	Thiazide-induced adverse metabolic effects in hypertensive patients	4.000000e-06
GCST003991_12	Childhood ear infection	1.000000e-08
GCST005013_62	Childhood ear infection	1.000000e-08
GCST008399_10	Cocaine dependence	4.000000e-06
GCST009438_5	Voxel-wise structural brain imaging measurements in Alzheimer’s disease	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs199755581	NIPAL2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	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
belinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Lactic Acid	decreases 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_D4H4	HCT116-NIPAL2-KO-c3	Cancer cell line	Male
CVCL_D4H5	HCT116-NIPAL2-KO-c5	Cancer cell line	Male

Clinical trials (associated diseases)

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