NIPAL4

NIPA like domain containing 4, the group of Solute carrier family 57, NIPA-like magnesium transporters

Basic information

Region (hg38): 5:157460213-157474722

Links

ENSG00000172548 ∙ NCBI:348938 ∙ OMIM:609383 ∙ HGNC:28018 ∙ Uniprot:Q0D2K0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive congenital ichthyosis 6 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 6 (Definitive), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 6 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 6 (Strong), mode of inheritance: AR
• lamellar ichthyosis (Supportive), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 6	AR	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	Dermatologic	15317751; 17557927; 20301593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NIPAL4 gene.

• not provided (6 variants)
• Autosomal recessive congenital ichthyosis 6 (6 variants)
• Lamellar ichthyosis (4 variants)
• Autosomal recessive congenital ichthyosis (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NIPAL4 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			6	5	4	15
missense	3	1	38	3	4	49
nonsense	4	2				6
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding			32	6	20	58
Total	8	5	76	14	28

Highest pathogenic variant AF is 0.000775

Variants in NIPAL4

This is a list of pathogenic ClinVar variants found in the NIPAL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-157460218-CTCGC-T		not specified	Uncertain significance (Dec 23, 2021)
5-157460220-C-A			Uncertain significance (Nov 30, 2023)
5-157460228-A-C		Inborn genetic diseases	Uncertain significance (Mar 21, 2023)
5-157460241-A-G			Uncertain significance (Aug 05, 2019)
5-157460250-G-A		Autosomal recessive congenital ichthyosis 6	Uncertain significance (Nov 06, 2017)
5-157460262-C-T			Benign (Apr 08, 2022)
5-157460300-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
5-157460324-G-T		Lamellar ichthyosis	Likely pathogenic (Sep 16, 2022)
5-157460331-G-A		not specified	Uncertain significance (Apr 11, 2024)
5-157460331-G-C		Inborn genetic diseases	Likely benign (Sep 14, 2023)
5-157460362-G-C		Autosomal recessive congenital ichthyosis 6	Pathogenic (May 16, 2019)
5-157460366-G-T			Likely benign (Jan 31, 2018)
5-157460381-C-G			Benign (Jun 19, 2021)
5-157460465-G-A			Benign (Jun 20, 2021)
5-157463148-A-G			Benign (Nov 11, 2023)
5-157463151-AC-A		Autosomal recessive congenital ichthyosis 6	Pathogenic (May 16, 2019)
5-157463152-C-A			Uncertain significance (Dec 11, 2023)
5-157463153-C-T		Inborn genetic diseases	Uncertain significance (Mar 23, 2022)
5-157463165-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
5-157463166-T-C		Autosomal recessive congenital ichthyosis 6 • NIPAL4-related disorder	Benign/Likely benign (Jul 27, 2023)
5-157463173-C-A		Inborn genetic diseases	Uncertain significance (Apr 09, 2023)
5-157463195-C-T			Pathogenic (Jan 02, 2024)
5-157463201-A-C		Autosomal recessive congenital ichthyosis 6	Uncertain significance (Jan 13, 2018)
5-157463210-C-G		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
5-157463249-C-T		Autosomal recessive congenital ichthyosis 6	Conflicting classifications of pathogenicity (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NIPAL4	protein_coding	protein_coding	ENST00000311946	6	14699

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00137	0.967	124632	0	21	124653	0.0000842

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	200	254	0.787	0.0000139	2979
Missense in Polyphen		73	96.047	0.76004		1145
Synonymous	1.17	99	115	0.862	0.00000711	1002
Loss of Function	1.89	7	14.9	0.470	7.83e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.00	0.00
East Asian	0.000446	0.000445
Finnish	0.0000958	0.0000928
European (Non-Finnish)	0.0000361	0.0000354
Middle Eastern	0.000446	0.000445
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Ba(2+), Mn(2+), Sr(2+) and Co(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. {ECO:0000250, ECO:0000269|PubMed:15317751}.
• Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Intolerance Scores

• loftool: 0.211
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.49

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.170
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.522

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nipal4
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

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