IMPDH1

inosine monophosphate dehydrogenase 1

Basic information

Region (hg38): 7:128392276-128410252

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 (459 variants)
• Leber congenital amaurosis 11 (79 variants)
• Retinitis pigmentosa (76 variants)
• Inborn genetic diseases (18 variants)
• Retinal dystrophy (16 variants)
• Retinitis pigmentosa 10 (11 variants)
• not specified (10 variants)
• Retinitis pigmentosa 10;Leber congenital amaurosis 11 (2 variants)
• Leber congenital amaurosis 11;Retinitis pigmentosa 10 (1 variants)
• IMPDH1-related condition (1 variants)
• IMPDH1-Related Disorders (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.

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			6	95	4	105
missense	4	4	182	3		193
nonsense			3			3
start loss						0
frameshift			6			6
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)			3			3
splice region			15	29	3	47
non coding			30	77	19	126
Total	4	4	233	176	23

Variants in IMPDH1

This is a list of pathogenic ClinVar variants found in the IMPDH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-128392285-G-A		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392286-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
7-128392313-G-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
7-128392365-C-T		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 12, 2018)
7-128392373-G-A		Retinitis pigmentosa • Leber congenital amaurosis 11	Benign (Jan 12, 2018)
7-128392376-G-A		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392394-A-G		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392410-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Benign (Jan 13, 2018)
7-128392463-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Likely benign (Jan 13, 2018)
7-128392597-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
7-128392686-C-A		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 13, 2018)
7-128392686-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392731-G-A		Leber congenital amaurosis 11 • Retinitis pigmentosa	Benign/Likely benign (Apr 27, 2017)
7-128392748-C-T		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392749-G-A		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392751-A-G		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 13, 2018)
7-128392776-G-C		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 13, 2018)
7-128392779-C-T		Retinitis pigmentosa • Leber congenital amaurosis 11	Benign/Likely benign (Jan 12, 2018)
7-128392784-G-A		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 12, 2018)
7-128392784-G-C		Leber congenital amaurosis 11 • Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 13, 2018)
7-128392784-G-T		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 13, 2018)
7-128392805-G-A		Leber congenital amaurosis 11 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-128392811-G-A		Retinitis pigmentosa • Leber congenital amaurosis 11	Conflicting classifications of pathogenicity (Jan 13, 2018)
7-128392839-C-T		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Jan 13, 2018)
7-128392870-C-G		Retinitis pigmentosa • Leber congenital amaurosis 11	Uncertain significance (Apr 27, 2017)

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 <i>de novo</i> biosynthesis;guanosine ribonucleotides <i>de novo</i> biosynthesis;purine nucleotides <i>de novo</i> 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