NIPA1

protein-coding

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

Gene summary

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. [provided by RefSeq, Nov 2008]

Previous symbols:

SPG6

MANE transcript

NM_144599.5

Inheritance

ClinVar variants

P:7U:111B:72

Top phenotype

Spastic paraplegia 6, autosomal dominant

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr15:22,773,063-22,829,789

External References & Databases

Ensembl (ENSG00000170113)

Transcript & Mutation Effects

hg38 • Region Span ~56.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegia 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010878

Submitter: Labcorp Genetics (formerly Invitae)

hereditary spastic paraplegia 6SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010878

Submitter: Orphanet

hereditary spastic paraplegia 6MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0010878

Submitter: Ambry Genetics

hereditary spastic paraplegia 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010878

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spastic paraplegia 6, autosomal dominantAD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 7854534; 14508710; 15711826; 21419568; 21599812; 22302102

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NIPA1 variants in ClinVar

9 Conditions Cataloged

Hereditary spastic paraplegia 6Total: 172

not providedTotal: 76

Inborn genetic diseasesTotal: 31

not specifiedTotal: 29

NIPA1-related disorderTotal: 14

Hereditary spastic paraplegiaTotal: 14

Spastic paraplegiaTotal: 2

Amyotrophic lateral sclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144599.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	65 clinvar	1 clinvar	69
missense	4 clinvar	3 clinvar	106 clinvar	5 clinvar	1 clinvar	119
nonsense						0
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	4	3	111	70	2	190

Highest pathogenic variant AF is 6.8485554e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144599.5	RefSeq	NP_653200.2	5	MANE Select
ENST00000337435.9	Ensembl	ENSP00000337452.4	5	MANE Select
NM_001142275.1	RefSeq	NP_001135747.1	4	Standard
ENST00000437912.6	Ensembl	ENSP00000393962.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prader-Willi and Angelman Syndrome
Transport of small molecules
Miscellaneous transport and binding events

Biological Process

magnesium ion transport
transmembrane transport
magnesium ion transmembrane transport

Molecular Function

magnesium ion transmembrane transporter activity

Cellular Component

early endosome
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337435
Coding exons: 5
Length: 56729
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	110	184	0.597	0.0000108	2073
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.263
RVIS EVS: -0.32
RVIS percentile EVS: 31.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.162

Gene Damage Prediction

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