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.

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.

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				2	6	8
missense			29	1	6	36
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					24	24
Total	0	0	30	3	36

Variants in PPIP5K2

This is a list of pathogenic ClinVar variants found in the PPIP5K2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-103129219-G-C			Benign (May 14, 2021)
5-103133552-T-C		not specified	Uncertain significance (Dec 01, 2022)
5-103133607-A-G		not specified	Uncertain significance (Jul 14, 2024)
5-103136737-C-G		not specified	Uncertain significance (Jun 07, 2023)
5-103136793-C-T		PPIP5K2-related disorder	Benign (Dec 23, 2019)
5-103136856-A-G			Benign (May 22, 2021)
5-103138463-C-G		not specified	Uncertain significance (Oct 27, 2023)
5-103138467-A-C		not specified	Uncertain significance (Jun 21, 2022)
5-103147827-T-A			Benign (May 14, 2021)
5-103147896-G-A			Benign (May 22, 2021)
5-103147973-C-T		Hearing loss, autosomal recessive 100	Uncertain significance (Oct 19, 2020)
5-103149252-A-T		not specified	Uncertain significance (Dec 13, 2023)
5-103149306-C-G		not specified	Uncertain significance (Oct 04, 2022)
5-103151019-G-C			Benign (May 14, 2021)
5-103151287-A-G		not specified	Uncertain significance (Sep 20, 2023)
5-103151311-T-G		not specified	Uncertain significance (Nov 20, 2023)
5-103151384-T-G		PPIP5K2-related disorder	Benign (Dec 23, 2019)
5-103152479-G-A			Benign (May 22, 2021)
5-103152485-C-T			Benign (May 20, 2021)
5-103152867-T-C			Benign (May 14, 2021)
5-103153807-T-G			Benign (May 14, 2021)
5-103153930-C-G		not specified	Uncertain significance (Dec 01, 2022)
5-103154707-T-G		PPIP5K2-related disorder	Benign (Mar 01, 2022)
5-103154708-C-T		not specified	Uncertain significance (Nov 10, 2024)
5-103154817-A-G			Benign (May 22, 2021)

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