PANK2

pantothenate kinase 2, the group of Pantothenate kinase family|MicroRNA protein coding host genes

Basic information

Region (hg38): 20:3888839-3929887

Previous symbols: [ "C20orf48", "NBIA1" ]

Links

ENSG00000125779 ∙ NCBI:80025 ∙ OMIM:606157 ∙ HGNC:15894 ∙ Uniprot:Q9BZ23 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pantothenate kinase-associated neurodegeneration (Strong), mode of inheritance: AR
• hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (Definitive), mode of inheritance: AR
• pantothenate kinase-associated neurodegeneration (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration; Neurodegeneration with brain iron accumulation 1	AD/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	Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	477009; 7158329; 3969211; 1447570; 1734303; 7885538; 7898702; 8944032; 11479594; 12058097; 12510040; 14638969; 15911822; 15642932; 16240131; 16437574; 16687521; 18981035; 20301663; 21286947

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PANK2 gene.

• Pigmentary pallidal degeneration (58 variants)
• not provided (9 variants)
• Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (4 variants)
• Retinitis pigmentosa (2 variants)
• Neurodegeneration (2 variants)
• Inborn genetic diseases (2 variants)
• Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration;Pigmentary pallidal degeneration (1 variants)
• PANK2-related disorder (1 variants)
• Dystonic disorder (1 variants)
• Pigmentary pallidal degeneration;Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PANK2 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			1	193	1	195
missense	14	21	172	9	1	217
nonsense	11	3	4			18
start loss				1		1
frameshift	29	7	1			37
inframe indel		2	4			6
splice donor/acceptor (+/-2bp)	5	6				11
splice region	1	1	4	14	1	21
non coding	3	1	17	84	23	128
Total	62	40	199	287	25

Highest pathogenic variant AF is 0.000217

Variants in PANK2

This is a list of pathogenic ClinVar variants found in the PANK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-3888963-G-A			Likely benign (Sep 11, 2018)
20-3889048-G-A			Likely benign (Jul 26, 2019)
20-3889079-G-C			Likely benign (Sep 26, 2018)
20-3889090-G-A		not specified • Pigmentary pallidal degeneration	Benign/Likely benign (Sep 05, 2018)
20-3889097-G-T		PANK2-related disorder	Likely benign (Mar 12, 2019)
20-3889107-A-C		Pigmentary pallidal degeneration	Likely benign (May 22, 2023)
20-3889109-G-A		Pigmentary pallidal degeneration	Likely benign (Dec 09, 2023)
20-3889109-G-T		Pigmentary pallidal degeneration • Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
20-3889112-C-G		Pigmentary pallidal degeneration	Likely benign (Sep 26, 2023)
20-3889112-C-T		Pigmentary pallidal degeneration	Conflicting classifications of pathogenicity (May 01, 2023)
20-3889114-G-A		Pigmentary pallidal degeneration	Uncertain significance (Apr 04, 2022)
20-3889118-C-T		Pigmentary pallidal degeneration	Likely benign (Aug 02, 2023)
20-3889124-C-T		Pigmentary pallidal degeneration	Likely benign (Oct 22, 2023)
20-3889130-C-T		Pigmentary pallidal degeneration • PANK2-related disorder	Likely benign (Oct 15, 2023)
20-3889131-G-A		Pigmentary pallidal degeneration	Uncertain significance (Jun 03, 2022)
20-3889134-C-T		Pigmentary pallidal degeneration • not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 08, 2024)
20-3889136-TTGGGCGGCGCCGCCATCACTCTCTTC-T		Pigmentary pallidal degeneration	Conflicting classifications of pathogenicity (Aug 23, 2022)
20-3889137-T-C		Pigmentary pallidal degeneration • Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
20-3889138-G-A		Pigmentary pallidal degeneration	Uncertain significance (Aug 09, 2022)
20-3889142-G-A		Pigmentary pallidal degeneration	Likely benign (Jul 16, 2023)
20-3889145-G-A		Pigmentary pallidal degeneration	Likely benign (Sep 18, 2023)
20-3889148-G-A		Pigmentary pallidal degeneration	Likely benign (Nov 10, 2023)
20-3889154-A-G		Pigmentary pallidal degeneration	Conflicting classifications of pathogenicity (Dec 12, 2023)
20-3889155-C-T		Pigmentary pallidal degeneration	Uncertain significance (Mar 11, 2021)
20-3889158-T-C		Pigmentary pallidal degeneration	Uncertain significance (May 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PANK2	protein_coding	protein_coding	ENST00000316562	7	38120

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.40e-7	0.909	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.179	298	307	0.971	0.0000165	3576
Missense in Polyphen		50	88.235	0.56667		1021
Synonymous	-2.36	163	129	1.26	0.00000696	1224
Loss of Function	1.68	13	21.4	0.608	0.00000111	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000380	0.000380
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000248	0.000246
Middle Eastern	0.000272	0.000272
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be the master regulator of the CoA biosynthesis. {ECO:0000250}.
• Disease: DISEASE: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP) [MIM:607236]: Rare syndrome with many clinical similarities to PKAN. {ECO:0000269|PubMed:12058097}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pantothenate and CoA biosynthesis - Homo sapiens (human);Coenzyme A biosynthesis;Vitamin B5 - CoA biosynthesis from pantothenate;Metabolism;Vitamin B5 (pantothenate) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;coenzyme A biosynthesis (Consensus)

Recessive Scores

• pRec: 0.192

Intolerance Scores

• loftool: 0.132
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.11

Haploinsufficiency Scores

• pHI: 0.461
• hipred: N
• hipred_score: 0.446
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pank2
• Phenotype: renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system 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); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: pank2
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: spatial pattern

Gene ontology

• Biological process: spermatid development;aerobic respiration;coenzyme biosynthetic process;coenzyme A biosynthetic process;pantothenate metabolic process;phosphorylation;regulation of fatty acid metabolic process;regulation of mitochondrial membrane potential;mitochondrion morphogenesis;regulation of triglyceride metabolic process;regulation of bile acid metabolic process
• Cellular component: nucleus;mitochondrion;mitochondrial intermembrane space;cytosol
• Molecular function: pantothenate kinase activity;ATP binding