IMPA1

inositol monophosphatase 1, the group of Phosphoinositide phosphatases

Basic information

Region (hg38): 8:81656914-81686331

Previous symbols: [ "IMPA" ]

Links

ENSG00000133731 ∙ NCBI:3612 ∙ OMIM:602064 ∙ HGNC:6050 ∙ Uniprot:P29218 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 59 (Limited), mode of inheritance: AR
• intellectual disability, autosomal recessive 59 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal recessive 59	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	Neurologic	26416544

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IMPA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IMPA1 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			19	1	1	21
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	19	2	2

Variants in IMPA1

This is a list of pathogenic ClinVar variants found in the IMPA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-81659368-G-A		Intellectual disability, autosomal recessive 59	Likely pathogenic (Aug 01, 2021)
8-81659377-G-A		not specified	Uncertain significance (May 04, 2022)
8-81659398-C-T		not specified	Uncertain significance (Apr 23, 2024)
8-81659399-T-C		not specified	Uncertain significance (Oct 28, 2024)
8-81659401-T-C		not specified	Uncertain significance (Jun 06, 2023)
8-81659413-A-C		not specified	Uncertain significance (Sep 02, 2024)
8-81659437-C-T		not specified	Likely benign (Jun 26, 2024)
8-81659442-C-T		not specified	Uncertain significance (Mar 28, 2024)
8-81659466-C-T		Intellectual disability, autosomal recessive 59	Uncertain significance (Mar 02, 2019)
8-81660549-T-A		not specified	Uncertain significance (Jun 24, 2022)
8-81660615-C-T		not specified	Uncertain significance (Jun 02, 2023)
8-81660616-G-A		not specified	Likely benign (Jul 15, 2024)
8-81660621-T-C		Intellectual disability, autosomal recessive 59 • not specified	Uncertain significance (Nov 22, 2022)
8-81670952-T-C		not specified	Uncertain significance (Dec 07, 2024)
8-81670969-A-G		not specified	Uncertain significance (Jul 15, 2021)
8-81671001-T-C			Likely benign (Sep 01, 2024)
8-81671008-G-A		not specified	Uncertain significance (Jun 09, 2022)
8-81671011-G-GAGCCC		Intellectual disability, autosomal recessive 59	Pathogenic (Apr 07, 2022)
8-81671045-T-C		not specified	Uncertain significance (Nov 08, 2022)
8-81673891-C-T		not specified	Uncertain significance (May 20, 2024)
8-81673919-C-G		Intellectual disability, autosomal recessive 59	Uncertain significance (Mar 12, 2018)
8-81673921-A-G		not specified	Uncertain significance (May 23, 2023)
8-81676257-T-C			Benign (Nov 01, 2024)
8-81676288-A-T			Benign (Dec 31, 2019)
8-81679182-G-T		IMPA1-related disorder	Likely benign (Jul 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IMPA1	protein_coding	protein_coding	ENST00000449740	9	28733

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000478	0.970	125731	0	7	125738	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.435	157	173	0.907	0.00000816	2183
Missense in Polyphen		44	63.075	0.69758		775
Synonymous	0.718	50	56.9	0.879	0.00000299	651
Loss of Function	1.93	8	16.5	0.486	7.93e-7	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000531	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo- inositol monophosphates, myo-inositol 1,3-diphosphate, myo- inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1- phosphate, beta-glycerophosphate, and 2'-AMP as substrates. {ECO:0000269|PubMed:17068342, ECO:0000269|PubMed:8718889, ECO:0000269|PubMed:9462881}.
• Disease: DISEASE: Mental retardation, autosomal recessive 59 (MRT59) [MIM:617323]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT59 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:26416544}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Inositol Phosphate Metabolism;Inositol Metabolism;Integrated Breast Cancer Pathway;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;Inositol phosphate metabolism;D-<i>myo</i>-inositol (1,4,5)-trisphosphate degradation;Metabolism;<i>myo</i>-inositol <i>de novo</i> biosynthesis;Inositol phosphate metabolism;Synthesis of IP2, IP, and Ins in the cytosol (Consensus)

Recessive Scores

• pRec: 0.390

Intolerance Scores

• loftool: 0.832
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.525
• hipred: N
• hipred_score: 0.145
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Impa1
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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: inositol biosynthetic process;phosphatidylinositol biosynthetic process;phosphate-containing compound metabolic process;signal transduction;inositol phosphate metabolic process;phosphatidylinositol phosphorylation;inositol phosphate dephosphorylation
• Cellular component: cytoplasm;cytosol
• Molecular function: magnesium ion binding;protein binding;inositol monophosphate 1-phosphatase activity;manganese ion binding;lithium ion binding;identical protein binding;protein homodimerization activity;inositol monophosphate 3-phosphatase activity;inositol monophosphate 4-phosphatase activity;inositol monophosphate phosphatase activity