IMPDH2

inosine monophosphate dehydrogenase 2

Basic information

Region (hg38): 3:49024324-49029447

Links

ENSG00000178035 ∙ NCBI:3615 ∙ OMIM:146691 ∙ HGNC:6053 ∙ Uniprot:P12268 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
IMPDH2 enzyme activity, variation in	AD	Pharmacogenomic	Variants may be involved in response to treatment with medications such as mycophenolate mofetil in individuals who have undergone transplants	Biochemical	17496727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IMPDH2 gene.

• not provided (12 variants)
• Inborn genetic diseases (8 variants)
• Dystonic disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IMPDH2 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						0
missense		2	15			17
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	2	17	0	1

Variants in IMPDH2

This is a list of pathogenic ClinVar variants found in the IMPDH2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-49024514-C-T		not specified	Uncertain significance (Aug 14, 2023)
3-49024547-C-G			Uncertain significance (Jun 27, 2023)
3-49024547-CAAACTT-C			Uncertain significance (Sep 07, 2023)
3-49024587-G-A		IMPDH2-related disorder	Likely benign (Sep 04, 2019)
3-49024741-T-C		not specified	Uncertain significance (Sep 14, 2022)
3-49025134-G-A			Uncertain significance (Dec 01, 2022)
3-49025182-C-T			Uncertain significance (Apr 01, 2023)
3-49025232-G-T			Uncertain significance (Sep 24, 2022)
3-49026365-C-T		not specified	Uncertain significance (Aug 04, 2023)
3-49026549-A-G		not specified	Uncertain significance (Dec 28, 2023)
3-49026677-A-G		IMPDH2-related disorder	Benign (Jan 21, 2021)
3-49026719-G-A		IMPDH2 enzyme activity, variation in	Affects (Apr 01, 2007)
3-49026756-A-C		not specified	Uncertain significance (Oct 04, 2022)
3-49026757-A-C			Uncertain significance (Aug 11, 2022)
3-49026791-C-G			Uncertain significance (Jun 24, 2021)
3-49026793-T-C			Likely pathogenic (Feb 24, 2022)
3-49026960-C-G			Uncertain significance (May 15, 2019)
3-49026965-T-C		not specified	Uncertain significance (Oct 12, 2022)
3-49027038-T-C		not specified	Uncertain significance (Jun 03, 2022)
3-49027052-G-A		IMPDH2-related disorder	Likely benign (Feb 14, 2020)
3-49027801-G-A		not specified	Uncertain significance (Sep 29, 2023)
3-49027859-G-A		not specified	Uncertain significance (Aug 02, 2021)
3-49027873-G-C		not specified	Uncertain significance (Dec 19, 2022)
3-49027903-C-T		Dystonic disorder	Likely pathogenic (Mar 17, 2021)
3-49028438-G-T			Uncertain significance (Mar 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IMPDH2	protein_coding	protein_coding	ENST00000326739	14	5084

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000436	0.991	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	176	297	0.592	0.0000173	3367
Missense in Polyphen		46	114.97	0.40011		1301
Synonymous	-0.931	123	111	1.11	0.00000597	1021
Loss of Function	2.35	13	25.9	0.502	0.00000129	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000517	0.000454
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000549	0.000544
Finnish	0.000198	0.000185
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000549	0.000544
South Asian	0.000392	0.000392
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate- limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
• Pathway: Drug metabolism - other enzymes - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Mycophenolic Acid Metabolism Pathway;Neutrophil degranulation;Metabolism of nucleotides;urate biosynthesis/inosine 5,-phosphate degradation;purine nucleotides degradation;Innate Immune System;Immune System;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;Purine ribonucleoside monophosphate biosynthesis;guanosine nucleotides <i>de novo</i> biosynthesis;guanosine ribonucleotides <i>de novo</i> biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.394

Intolerance Scores

• loftool: 0.581
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.965
• hipred: Y
• hipred_score: 0.701
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Impdh2
• Phenotype: immune system phenotype; cellular phenotype; hematopoietic 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)

Zebrafish Information Network

• Gene name: impdh2
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: GMP biosynthetic process;GTP biosynthetic process;circadian rhythm;purine ribonucleoside monophosphate biosynthetic process;neutrophil degranulation;lymphocyte proliferation;protein homotetramerization;oxidation-reduction process;retina development in camera-type eye;cellular response to interleukin-4
• Cellular component: extracellular region;nucleus;cytoplasm;peroxisomal membrane;cytosol;membrane;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: nucleotide binding;DNA binding;RNA binding;IMP dehydrogenase activity;protein binding;metal ion binding