IPMK

inositol polyphosphate multikinase

Basic information

Region (hg38): 10:58191516-58267894

Links

ENSG00000151151 ∙ NCBI:253430 ∙ OMIM:609851 ∙ HGNC:20739 ∙ Uniprot:Q8NFU5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary neuroendocrine tumor of small intestine (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Small intestinal carcinoid, hereditary	AD	Oncologic	Individuals have been described as at high risk of small intestinal carcinoid tumors, and awareness may allow surveillance and prompt management	Oncologic	25865046

ClinVar

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

• Inborn genetic diseases (23 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IPMK 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	1
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	23	0	1

Variants in IPMK

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

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

Position	Type	Phenotype	Significance	ClinVar
10-58196090-T-C		not specified	Uncertain significance (Jun 22, 2023)
10-58196353-T-C		not specified	Uncertain significance (Feb 10, 2022)
10-58196371-G-A		not specified	Uncertain significance (Jul 13, 2021)
10-58196425-G-A		not specified	Uncertain significance (Jan 26, 2022)
10-58196428-G-A		not specified	Uncertain significance (Mar 24, 2023)
10-58196481-T-A		not specified	Uncertain significance (May 05, 2023)
10-58196487-T-G		not specified	Uncertain significance (Aug 08, 2023)
10-58196509-A-G		not specified	Uncertain significance (May 26, 2022)
10-58196597-T-C		not specified	Uncertain significance (Dec 28, 2023)
10-58196644-G-A		not specified	Uncertain significance (Dec 27, 2023)
10-58199249-T-C		not specified	Uncertain significance (Jan 23, 2023)
10-58199273-C-T		not specified	Uncertain significance (Dec 02, 2022)
10-58199303-C-T		not specified	Uncertain significance (Sep 22, 2022)
10-58199318-A-G		not specified	Uncertain significance (Nov 02, 2023)
10-58216171-T-C		not specified	Uncertain significance (Aug 14, 2023)
10-58216171-T-G		not specified	Uncertain significance (Dec 06, 2021)
10-58216278-T-A		not specified	Uncertain significance (Dec 21, 2023)
10-58227044-G-A			Benign (May 15, 2018)
10-58227061-G-A		not specified	Uncertain significance (Jan 26, 2022)
10-58227073-C-T		not specified	Uncertain significance (Jul 13, 2022)
10-58237732-A-T		not specified	Uncertain significance (Dec 05, 2022)
10-58267434-T-C		not specified	Uncertain significance (Apr 07, 2022)
10-58267473-C-T		not specified	Uncertain significance (Sep 06, 2022)
10-58267485-G-A		not specified	Uncertain significance (May 11, 2022)
10-58267516-G-C			Benign (May 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IPMK	protein_coding	protein_coding	ENST00000373935	6	76417

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.963	0.0374	125712	0	8	125720	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.773	183	215	0.852	0.0000100	2723
Missense in Polyphen		34	58.356	0.58263		740
Synonymous	-0.731	91	82.6	1.10	0.00000397	772
Loss of Function	3.62	2	19.1	0.105	9.90e-7	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000356	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inositol phosphate kinase with a broad substrate specificity. Has a preference for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (PubMed:12027805, PubMed:12223481). Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:29883610). {ECO:0000269|PubMed:12027805, ECO:0000269|PubMed:12223481, ECO:0000269|PubMed:29883610}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Inositol Phosphate Metabolism;Inositol Metabolism;D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;D-<i>myo</i>-inositol (3,4,5,6)-tetrakisphosphate biosynthesis;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);Inositol phosphate metabolism;inositol pyrophosphates biosynthesis;Metabolism;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;Synthesis of IPs in the nucleus;D-<i>myo</i>-inositol (1,4,5,6)-tetrakisphosphate biosynthesis;Inositol phosphate metabolism;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis V (from Ins(1,3,4)P3) (Consensus)

Recessive Scores

• pRec: 0.0941

Intolerance Scores

• loftool: 0.228
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.74

Haploinsufficiency Scores

• pHI: 0.510
• hipred: Y
• hipred_score: 0.701
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.841

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ipmk
• 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); embryo 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ipmkb
• Affected structure: cranium
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: phosphorylation;inositol phosphate biosynthetic process;inositol phosphate metabolic process;necroptotic process
• Cellular component: nucleus;nucleoplasm;nucleolus
• Molecular function: inositol-1,4,5-trisphosphate 6-kinase activity;inositol tetrakisphosphate 3-kinase activity;inositol tetrakisphosphate 6-kinase activity;ATP binding;inositol-1,4,5-trisphosphate 3-kinase activity;inositol tetrakisphosphate 5-kinase activity