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 (153 variants)
• not_provided (58 variants)
• Inborn_genetic_diseases (29 variants)
• not_specified (15 variants)
• Hereditary_spastic_paraplegia (14 variants)
• NIPA1-related_disorder (8 variants)
• Spastic_paraplegia,_autosomal_dominant (2 variants)
• Spastic_paraplegia (2 variants)
• See_cases (1 variants)
• Amyotrophic_lateral_sclerosis (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. These statistics are base on transcript: NM_000144599.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	57	1	61
missense	4	1	93	3	1	102
nonsense						0
start loss			1			1
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	4	1	98	60	2

Highest pathogenic variant AF is 6.84856e-7

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