PPIP5K2

diphosphoinositol pentakisphosphate kinase 2, the group of Cilia and flagella associated

Basic information

Region (hg38): 5:103120149-103212799

Previous symbols: [ "HISPPD1", "DFNB100" ]

Links

ENSG00000145725

∙ NCBI:23262 ∙ OMIM:611648 ∙ HGNC:29035 ∙ Uniprot:O43314 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hearing loss, autosomal recessive 100 (Moderate), mode of inheritance: AR
hearing loss, autosomal recessive 100 (Limited), mode of inheritance: AR
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
hearing loss, autosomal recessive 100 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 100	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	29590114

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPIP5K2 gene.

not_specified (89 variants)
not_provided (13 variants)
PPIP5K2-related_disorder (10 variants)
Hearing_loss,_autosomal_recessive_100 (2 variants)
Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPIP5K2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001276277.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	5 clinvar	7
missense			89 clinvar	1 clinvar	4 clinvar	94
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	91	3	9

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPIP5K2	protein_coding	protein_coding	ENST00000321521	29	92648

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.58e-21	0.983	125631	0	117	125748	0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.80	375	647	0.579	0.0000336	8012
Missense in Polyphen		63	206.36	0.3053		2523
Synonymous	0.806	197	212	0.930	0.0000105	2281
Loss of Function	2.78	43	67.7	0.636	0.00000402	846

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000974	0.000972
Ashkenazi Jewish	0.000217	0.000198
East Asian	0.00111	0.00109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000481	0.000475
Middle Eastern	0.00111	0.00109
South Asian	0.000510	0.000457
Other	0.000861	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis- diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at positions 1 or 3 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates at position 1 or 3 PP-InsP5, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752}.;
Pathway: Phosphatidylinositol signaling system - Homo sapiens (human);inositol pyrophosphates biosynthesis;Metabolism;superpathway of inositol phosphate compounds;Synthesis of pyrophosphates in the cytosol;Inositol phosphate metabolism (Consensus)

Recessive Scores

pRec: 0.114

Intolerance Scores

loftool: 0.918
rvis_EVS: -0.19
rvis_percentile_EVS: 39.24

Haploinsufficiency Scores

pHI: 0.102
hipred: Y
hipred_score: 0.706
ghis: 0.601

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ppip5k2
Phenotype: hearing/vestibular/ear 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);

Gene ontology

Biological process: inositol metabolic process;phosphorylation;inositol phosphate biosynthetic process;inositol phosphate metabolic process
Cellular component: cytosol
Molecular function: inositol-1,3,4,5,6-pentakisphosphate kinase activity;inositol hexakisphosphate kinase activity;inositol heptakisphosphate kinase activity;inositol hexakisphosphate 5-kinase activity;ATP binding;diphosphoinositol-pentakisphosphate kinase activity;inositol hexakisphosphate 1-kinase activity;inositol hexakisphosphate 3-kinase activity;5-diphosphoinositol pentakisphosphate 3-kinase activity