IMPDH1

inosine monophosphate dehydrogenase 1

Basic information

Region (hg38): 7:128392277-128409986

Previous symbols: [ "RP10" ]

Links

ENSG00000106348

∙ NCBI:3614 ∙ OMIM:146690 ∙ HGNC:6052 ∙ Uniprot:P20839 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

retinitis pigmentosa 10 (Moderate), mode of inheritance: AD
retinitis pigmentosa (Supportive), mode of inheritance: AD
Leber congenital amaurosis (Supportive), mode of inheritance: AD
retinitis pigmentosa 10 (Definitive), mode of inheritance: AD
Leber congenital amaurosis 11 (Definitive), mode of inheritance: AD
Leber congenital amaurosis 11 (Limited), mode of inheritance: AD
retinitis pigmentosa 10 (Strong), mode of inheritance: AD
inherited retinal dystrophy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 10; Leber congenital amaurosis 11	AD	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	Ophthalmologic	11875050; 11875049; 16384941; 20006823; 20238028; 20301475; 21791244

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IMPDH1 gene.

not_provided (542 variants)
Retinal_dystrophy (75 variants)
Leber_congenital_amaurosis_11 (51 variants)
Inborn_genetic_diseases (45 variants)
Retinitis_pigmentosa (43 variants)
Retinitis_pigmentosa_10 (26 variants)
IMPDH1-related_disorder (14 variants)
not_specified (11 variants)
Leber_congenital_amaurosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IMPDH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000883.4. 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			12 clinvar	135 clinvar	4 clinvar	151
missense	5 clinvar	15 clinvar	241 clinvar	19 clinvar		280
nonsense	6 clinvar	1 clinvar	1 clinvar			8
start loss						0
frameshift	7 clinvar	2 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)		5 clinvar	2 clinvar			7
Total	18	23	257	154	4

Highest pathogenic variant AF is 0.000261415

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IMPDH1	protein_coding	protein_coding	ENST00000338791	17	17976

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000578	0.999	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.69	261	350	0.745	0.0000227	3836
Missense in Polyphen		64	111.42	0.57443		1355
Synonymous	-0.673	155	145	1.07	0.0000101	1239
Loss of Function	2.83	14	31.0	0.451	0.00000173	350

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000754	0.000739
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.000109	0.000109
South Asian	0.0000981	0.0000980
Other	0.000494	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.;
Disease: DISEASE: Retinitis pigmentosa 10 (RP10) [MIM:180105]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:11875049, ECO:0000269|PubMed:11875050, ECO:0000269|PubMed:16384941}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 11 (LCA11) [MIM:613837]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:16384941}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Drug metabolism - other enzymes - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;Mycophenolic Acid Metabolism Pathway;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Mercaptopurine Metabolism Pathway;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Nucleotide Metabolism;Purine metabolism;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 de novo biosynthesis;guanosine ribonucleotides de novo biosynthesis;purine nucleotides de novo biosynthesis (Consensus)

Recessive Scores

pRec: 0.0985

Intolerance Scores

loftool: 0.0617
rvis_EVS: -0.24
rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

pHI: 0.696
hipred: Y
hipred_score: 0.589
ghis: 0.536

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0749

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Impdh1
Phenotype: immune system phenotype; vision/eye phenotype; hematopoietic system phenotype; cellular phenotype;

Zebrafish Information Network

Gene name: impdh1a
Affected structure: iridophore
Phenotype tag: abnormal
Phenotype quality: absent

Gene ontology

Biological process: GMP biosynthetic process;GTP biosynthetic process;purine ribonucleoside monophosphate biosynthetic process;neutrophil degranulation;lymphocyte proliferation;oxidation-reduction process
Cellular component: extracellular region;nucleus;cytoplasm;cytosol;secretory granule lumen;azurophil granule lumen;ficolin-1-rich granule lumen
Molecular function: nucleotide binding;nucleic acid binding;DNA binding;RNA binding;IMP dehydrogenase activity;metal ion binding