NIPA1

NIPA magnesium transporter 1, the group of Solute carrier family 57, NIPA-like magnesium transporters

Basic information

Region (hg38): 15:22773063-22829789

Previous symbols: [ "SPG6" ]

Links

ENSG00000170113 ∙ NCBI:123606 ∙ OMIM:608145 ∙ HGNC:17043 ∙ Uniprot:Q7RTP0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 6 (Moderate), mode of inheritance: AD
• hereditary spastic paraplegia 6 (Supportive), mode of inheritance: AD
• hereditary spastic paraplegia 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 6, autosomal dominant	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	7854534; 14508710; 15711826; 21419568; 21599812; 22302102

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NIPA1 gene.

• Hereditary spastic paraplegia 6 (4 variants)
• Hereditary spastic paraplegia (1 variants)
• not provided (1 variants)
• Spastic paraplegia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NIPA1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	45	2	50
missense	4		72	1	1	78
nonsense						0
start loss			1			1
frameshift						0
inframe indel			9	6	1	16
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding			80	29	57	166
Total	4	0	165	81	61

Variants in NIPA1

This is a list of pathogenic ClinVar variants found in the NIPA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-22786298-C-G			Benign (Jun 16, 2018)
15-22786362-G-C			Likely benign (Jan 28, 2019)
15-22786446-CG-C			Benign (Sep 20, 2019)
15-22786638-G-A		Spastic paraplegia, autosomal dominant	Uncertain significance (Jun 14, 2016)
15-22786647-C-G		NIPA1-related disorder	Likely benign (Jun 15, 2022)
15-22786657-A-G		Hereditary spastic paraplegia 6	Uncertain significance (Jan 12, 2018)
15-22786662-G-C		Hereditary spastic paraplegia 6	Likely benign (Sep 15, 2022)
15-22786663-ACTGCAG-A		Hereditary spastic paraplegia 6	Uncertain significance (Sep 26, 2023)
15-22786664-C-T		Hereditary spastic paraplegia 6	Uncertain significance (Oct 24, 2023)
15-22786665-TGCAGCTGCG-T		Hereditary spastic paraplegia 6	Uncertain significance (Jun 15, 2023)
15-22786667-C-T		Hereditary spastic paraplegia	Uncertain significance (Dec 12, 2016)
15-22786669-G-T			Uncertain significance (Dec 24, 2019)
15-22786670-C-T		Hereditary spastic paraplegia 6	Uncertain significance (Dec 30, 2023)
15-22786671-TGCGGCA-T		Hereditary spastic paraplegia 6 • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Oct 13, 2023)
15-22786671-TGCGGCAGCG-T		Hereditary spastic paraplegia 6	Uncertain significance (Oct 17, 2022)
15-22786671-TGCGGCAGCGGCGGCG-T		Hereditary spastic paraplegia 6	Uncertain significance (Jul 17, 2023)
15-22786671-TGCGGCAGCGGCGGCGGCG-T		Hereditary spastic paraplegia 6	Uncertain significance (Jan 21, 2023)
15-22786671-TGCGGCAGCGGCGGCGGCGGCGGCGGCG-T		Hereditary spastic paraplegia 6	Uncertain significance (Nov 07, 2023)
15-22786671-T-TGCGGCA		Hereditary spastic paraplegia 6	Benign (Aug 09, 2022)
15-22786673-C-A		Hereditary spastic paraplegia 6	Uncertain significance (Mar 16, 2018)
15-22786673-C-G		not specified • Hereditary spastic paraplegia 6	Conflicting classifications of pathogenicity (Dec 14, 2023)
15-22786673-C-T		Hereditary spastic paraplegia 6	Uncertain significance (Nov 27, 2023)
15-22786674-GGCA-G		Hereditary spastic paraplegia 6 • Hereditary spastic paraplegia	Benign/Likely benign (Apr 07, 2023)
15-22786675-G-A		Hereditary spastic paraplegia 6	Uncertain significance (Aug 12, 2021)
15-22786676-C-T		Hereditary spastic paraplegia 6	Uncertain significance (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NIPA1	protein_coding	protein_coding	ENST00000337435	5	56729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00587	0.912	125738	0	9	125747	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	110	184	0.597	0.0000108	2073
Missense in Polyphen		24	53.597	0.44779		601
Synonymous	-1.32	107	90.9	1.18	0.00000649	725
Loss of Function	1.49	5	10.1	0.495	4.30e-7	125

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Mn(2+) and Co(2+) but to a much less extent than Mg(2+) (By similarity). {ECO:0000250}.
• Pathway: Prader-Willi and Angelman Syndrome;Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.263
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.424
• hipred: Y
• hipred_score: 0.607
• ghis: 0.610

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.162

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nipa1
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: magnesium ion transport;transmembrane transport;magnesium ion transmembrane transport
• Cellular component: early endosome;plasma membrane;integral component of membrane
• Molecular function: magnesium ion transmembrane transporter activity