IMPDH1

Chr 7AD

inosine monophosphate dehydrogenase 1

Also known as: IMPD, IMPD1, IMPDH-I, LCA11, RP10, sWSS2608

NCBI Gene: 3614ENSG00000106348UniProt: P20839

The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Primary Disease Associations & Inheritance

Leber congenital amaurosis 11MIM #613837
AD
Retinitis pigmentosa 10MIM #180105
AD
590
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IMPDH1
🧬
Gene-Disease Validity (ClinGen)
IMPDH1-related retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 311 VUS of 590 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.000
Z-score 2.83
OE 0.45 (0.30–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.69Z-score
OE missense 0.75 (0.67–0.83)
261 obs / 350.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.30–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 14 / 31.0Missense obs/exp: 261 / 350.1Syn Z: -0.67

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic16
VUS311
Likely Benign178
Benign20
Conflicting38
27
Pathogenic
16
Likely Pathogenic
311
VUS
178
Likely Benign
20
Benign
38
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
17
0
27
Likely Pathogenic
5
8
3
0
16
VUS
3
241
57
10
311
Likely Benign
0
2
86
90
178
Benign
0
0
14
6
20
Conflicting
—38
Total16253177106590

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IMPDH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

IMPDH1-related Leber cogenital amaurosis

definitive
ADUndeterminedUncertain
Eye
G2P ↗

IMPDH1-related retinitis pigmentosa

definitive
ADDominant NegativeAltered Gene Product Structure
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leber congenital amaurosis 11

MIM #613837

Molecular basis of disorder known

Autosomal dominant

Retinitis pigmentosa 10

MIM #180105

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — IMPDH1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy.
Birtel J et al.·Sci Rep
2018Cohort
IMPDH1-associated autosomal dominant retinitis pigmentosa: natural history of novel variant Lys314Gln and a comprehensive literature search.
Sakti DH et al.·Ophthalmic Genet
2023Review
Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.
Wang L et al.·Int J Oral Sci
2024
c-Myc-IMPDH1/2 axis promotes tumourigenesis by regulating GTP metabolic reprogramming.
Zhang Q et al.·Clin Transl Med
2023
Novel Variant IMPDH1 c.134A>G, p.(Tyr45Cys): Phenotype-Genotype Correlation Revealed Likely Benign Clinical Significance.
Bjeloš M et al.·Int J Mol Sci
2023Case report
Impdh1 was identified as a key protein promotes diabetic vasculopathy by intervention of vascular endothelial cell pyroptosis.
Xie R et al.·BMC Cardiovasc Disord
2025
Clinical phenotype in a Swedish family with a mutation in the IMPDH1 gene.
Schatz P et al.·Ophthalmic Genet
2005
Inosine monophosphate dehydrogenase type1 sustains tumor growth in hepatocellular carcinoma.
Jia X et al.·J Clin Lab Anal
2022
Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.
Luce A et al.·J Transl Med
2025
Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis.
Bowne SJ et al.·Invest Ophthalmol Vis Sci
2006
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools