NIPAL4 (NIPA like domain containing 4)

Gene

• Entrez ID: 348938
• Gene name: NIPA like domain containing 4
• Gene symbol: NIPAL4
• Synonyms (NCBI Gene): ARCI6, ICHTHYIN, ICHYN, NIPA4, SLC57A6
• Chromosome: 5
• Chromosome location: 5q33.3
• Summary: This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs188020393	C>G,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant, 5 prime UTR variant
rs199422216	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, 5 prime UTR variant, stop gained
rs199422217	C>A,G	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs370356566	G>A	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs371608909	A>C,G	Pathogenic	Synonymous variant, missense variant, coding sequence variant, 5 prime UTR variant
rs373501601	C>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs375688767	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs376074083	G>A,T	Pathogenic	Intron variant
rs750991783	C>G	Pathogenic	Coding sequence variant, missense variant
rs757041309	G>A	Pathogenic	Missense variant, coding sequence variant
rs775903553	G>A,T	Pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant
rs777992589	C>G,T	Pathogenic	Coding sequence variant, stop gained, synonymous variant, 5 prime UTR variant
rs886060339	C>A,T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant, synonymous variant
rs900769357	G>A	Pathogenic	5 prime UTR variant, intron variant, missense variant, coding sequence variant
rs1027052344	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs1212378071	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1255386092	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1561831443	ATACATG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1561831582	G>A	Pathogenic	Splice donor variant
rs1581265561	C>-	Pathogenic	5 prime UTR variant, coding sequence variant, frameshift variant
rs1581265715	T>A	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs1581269752	G>A	Pathogenic	Splice donor variant
rs1581271844	C>-	Pathogenic	Intron variant
rs1581271869	C>T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs1581272003	C>G	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant
rs1581272834	C>G	Pathogenic	Missense variant, coding sequence variant
rs1581273254	A>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1185681	hsa-miR-122	CLIP-seq
MIRT1185682	hsa-miR-1237	CLIP-seq
MIRT1185683	hsa-miR-3135b	CLIP-seq
MIRT1185684	hsa-miR-3179	CLIP-seq
MIRT1185685	hsa-miR-3202	CLIP-seq
MIRT1185686	hsa-miR-3616-3p	CLIP-seq
MIRT1185687	hsa-miR-3652	CLIP-seq
MIRT1185688	hsa-miR-3936	CLIP-seq
MIRT1185689	hsa-miR-423-3p	CLIP-seq
MIRT1185690	hsa-miR-4263	CLIP-seq
MIRT1185691	hsa-miR-4271	CLIP-seq
MIRT1185692	hsa-miR-4297	CLIP-seq
MIRT1185693	hsa-miR-4430	CLIP-seq
MIRT1185694	hsa-miR-4436b-3p	CLIP-seq
MIRT1185695	hsa-miR-4654	CLIP-seq
MIRT1185696	hsa-miR-4659a-3p	CLIP-seq
MIRT1185697	hsa-miR-4659b-3p	CLIP-seq
MIRT1185698	hsa-miR-4716-3p	CLIP-seq
MIRT1185699	hsa-miR-4718	CLIP-seq
MIRT1185700	hsa-miR-4725-3p	CLIP-seq
MIRT1185701	hsa-miR-4727-5p	CLIP-seq
MIRT1185702	hsa-miR-4733-5p	CLIP-seq
MIRT1185703	hsa-miR-4747-5p	CLIP-seq
MIRT1185704	hsa-miR-4755-3p	CLIP-seq
MIRT1185705	hsa-miR-4769-3p	CLIP-seq
MIRT1185706	hsa-miR-4769-5p	CLIP-seq
MIRT1185707	hsa-miR-515-5p	CLIP-seq
MIRT1185708	hsa-miR-541	CLIP-seq
MIRT1185709	hsa-miR-542-5p	CLIP-seq
MIRT1185710	hsa-miR-576-5p	CLIP-seq
MIRT1185711	hsa-miR-605	CLIP-seq
MIRT1185712	hsa-miR-625	CLIP-seq
MIRT1185713	hsa-miR-654-5p	CLIP-seq
MIRT1185714	hsa-miR-942	CLIP-seq
MIRT1185715	hsa-miR-4268	CLIP-seq
MIRT1185716	hsa-miR-4448	CLIP-seq
MIRT1185701	hsa-miR-4727-5p	CLIP-seq
MIRT1185702	hsa-miR-4733-5p	CLIP-seq
MIRT1185705	hsa-miR-4769-3p	CLIP-seq
MIRT1185711	hsa-miR-605	CLIP-seq
MIRT1551758	hsa-miR-138	CLIP-seq
MIRT1551759	hsa-miR-3157-5p	CLIP-seq
MIRT1551760	hsa-miR-4676-5p	CLIP-seq
MIRT1551761	hsa-miR-4691-3p	CLIP-seq
MIRT1551762	hsa-miR-575	CLIP-seq
MIRT1551763	hsa-miR-622	CLIP-seq
MIRT2053831	hsa-miR-3158-5p	CLIP-seq
MIRT2053832	hsa-miR-3166	CLIP-seq
MIRT2053833	hsa-miR-3180-5p	CLIP-seq
MIRT1185701	hsa-miR-4727-5p	CLIP-seq
MIRT1185705	hsa-miR-4769-3p	CLIP-seq
MIRT2053834	hsa-miR-4771	CLIP-seq
MIRT2053835	hsa-miR-642a	CLIP-seq
MIRT2053836	hsa-miR-665	CLIP-seq
MIRT2283000	hsa-miR-1296	CLIP-seq
MIRT2283001	hsa-miR-2909	CLIP-seq
MIRT2053831	hsa-miR-3158-5p	CLIP-seq
MIRT2053832	hsa-miR-3166	CLIP-seq
MIRT2283002	hsa-miR-4512	CLIP-seq
MIRT1185701	hsa-miR-4727-5p	CLIP-seq
MIRT2053834	hsa-miR-4771	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005886	Component	Plasma membrane	IEA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0015095	Function	Magnesium ion transmembrane transporter activity	IEA
GO:0015693	Process	Magnesium ion transport	IBA
GO:0015693	Process	Magnesium ion transport	IEA
GO:0016020	Component	Membrane	IBA
GO:0016020	Component	Membrane	IEA
GO:1903830	Process	Magnesium ion transmembrane transport	IEA

Other IDs

• MIM: 609383
• HGNC: 28018
• e!Ensembl: ENSG00000172548

Protein

• UniProt ID: Q0D2K0
• Protein name: Magnesium transporter NIPA4 (Ichthyin) (NIPA-like protein 4) (Non-imprinted in Prader-Willi/Angelman syndrome region protein 4)
• Protein function: Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Ba(2+), Sr(2+) and Fe(2+) but to a much less extent than Mg(2+) (By similarity). May be a receptor for ligands (trioxilins A3 and B3) from the hepoxilin pathway (Pub
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF05653	Mg_trans_NIPA	116 → 410	Magnesium transporter NIPA	Family

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in brain, lung, stomach, keratinocytes and leukocytes, and in all other tissues tested except liver, thyroid and fetal brain. {ECO:0000269|PubMed:15317751, ECO:0000269|PubMed:17557927}.
• Sequence:

  MPGDSSPGTLPLWDASLSPPLGPDPGGFSRASHAGDKSRPPAPELGSPGAVRPRVGSCAP
  GPMELRVSNTSCENGSLLHLYCSSQEVLCQIVNDLSPEVPSNATFHSWQERIRQNYGFYI
  GLGLAFLSSFLIGSSVILKKKGLLRLVATGATRAVDGGFGYLKDAMWWAGFLTMAAGEVA
  NFGAYAFAPATVVTPLGALSVLISAILSSYFLRESLNLLGKLGCVICVAGSTVMVIHAPE
  EEKVTTIMEMASKMKDTGFIVFAVLLLVSCLILIFVIAPRYGQRNILIYIIICSVIGAFS
  VAAVKGLGITIKNFFQGLPVVRHPLPYILSLILALSLSTQVNFLNRALDIFNTSLVFPIY
  YVFFTTVVVTSSIILFKEWYSMSAVDIAGTLSGFVTIILGVFMLHAFKDLDISCASLPHM
  HKNPPPSPAPEPTVIRLEDKNVLVDNIELASTSSPEEKPKVFIIHS

• Sequence length: 466

Pathways

Reactome:

Miscellaneous transport and binding events

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal recessive congenital ichthyosis	Likely pathogenic; Pathogenic	rs199422217, rs370356566	RCV001729333 RCV001729571	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Autosomal recessive congenital ichthyosis 6	Pathogenic; Likely pathogenic	rs199422216, rs199422217, rs1561831582, rs1754350429, rs1754471135, rs370356566, rs1561831443, rs373501601, rs1581262988, rs1581265561, rs775903553, rs900769357, rs371608909, rs777992589, rs1581271869, rs1581272003, rs1212378071, rs1027052344, rs375688767, rs1581272834, rs886060339, rs1581273254, rs1452328130, rs1581269752, rs1581271844	RCV000001799 RCV000001801 RCV000001802 RCV003134504 RCV004515761 RCV000791228 RCV000782390 RCV000782389 RCV000791216 RCV000791218 RCV000791220 RCV000791222 RCV000791223 RCV000791224 RCV000791227 RCV000791229 RCV000791231 RCV000791232 RCV000791234 RCV000791235 RCV000791236 RCV000791237 RCV000791217 RCV000791225 RCV000791226	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Erythrokeratodermia variabilis et progressiva 1	Likely pathogenic	rs2113670056	RCV001530404	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ichthyosis and erythrokeratoderma	Likely pathogenic; Pathogenic	rs199422217	RCV006249351	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lamellar ichthyosis	Pathogenic; Likely pathogenic	rs199422216, rs199422217, rs1258173126, rs2532907239, rs370356566, rs375688767	RCV004579514 RCV001844003 RCV002302480 RCV002470008 RCV001797712 RCV003155312	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital ichthyosiform erythroderma	Uncertain significance; Likely benign	ClinVar Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONGENITAL NON-BULLOUS ICHTHYOSIFORM ERYTHRODERMA	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NONBULLOUS ICHTHYOSIFORM ERYTHRODERMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NIPAL4-related disorder	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arthropathy	Arthropathy	BEFREE	31532840		★☆☆☆☆ Found in Text Mining only
Chronic otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ichthyosis	Congenital Ichthyosis	BEFREE	20016120, 26456858, 28122049, 29174370, 31347739, 31532840, 31836270		★☆☆☆☆ Found in Text Mining only
Congenital non-bullous ichthyosiform erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	BEFREE	20016120, 22098531, 26456858, 28122049, 29174370, 31347739, 31532840, 31836270		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	ORPHANET_DG	20016120, 22739337		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Corneal erosion	Corneal erosion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectropion	Ectropion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Erythrokeratodermia Variabilis	Erythrokeratodermia variabilis	Pubtator	34669720	Associate	★☆☆☆☆ Found in Text Mining only
Exfoliative dermatitis	Exfoliative Dermatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gangrene	Gangrene	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperkeratosis	Hyperkeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypohidrosis	Hypohidrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypotrichosis	Hypotrichosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	LHGDN	15317751		★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	BEFREE	29174370		★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma Congenital	Congenital ichthyosiform erythroderma	Pubtator	31876100	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	BEFREE	20016120, 22098531, 26456858, 28122049, 29174370, 31347739, 31532840, 31836270		★☆☆☆☆ Found in Text Mining only
Ichthyosis	Ichthyosis	Pubtator	27025581, 34983512	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosis Lamellar	Lamellar ichthyosis	Pubtator	19197536, 20016120	Associate	★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 6	Ichthyosis with hypotrichosis	UNIPROT_DG	15317751, 17557927, 26456858		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 6	Ichthyosis with hypotrichosis	CLINVAR_DG	15317751, 17557927, 20016120, 22622417, 24397709, 25458912, 26762237		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 6	Ichthyosis with hypotrichosis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 6	Ichthyosis with hypotrichosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratitis	Keratitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lamellar ichthyosis	Lamellar ichthyosis	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Lamellar ichthyosis type 3	Lamellar ichthyosis	Pubtator	17557927, 20016120, 22622417, 30600594, 34983512, 36980989	Associate	★☆☆☆☆ Found in Text Mining only
Osteogenesis imperfecta type 3	Osteogenesis imperfecta	Pubtator	17557927	Associate	★☆☆☆☆ Found in Text Mining only
Parakeratosis	Parakeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	35757399	Associate	★☆☆☆☆ Found in Text Mining only