IMPDH2

Chr 3

inosine monophosphate dehydrogenase 2

Also known as: IMPD2, IMPDH-II

NCBI Gene: 3615 ENSG00000178035 UniProt: P12268

This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.35

OE 0.50 (0.33–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.50Z-score

OE missense 0.59 (0.52–0.67)

176 obs / 297.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.50 (0.33–0.80)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 13 / 25.9Missense obs/exp: 176 / 297.5Syn Z: -0.93

Background carrier burden — how many people carry a rare variant somewhere in IMPDH2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

537 rare PASS variants

Rare truncating (LoF)

1 in 1,200

115 rare PASS variants

Rare synonymous (reference)

1 in 200

303 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IMPDH2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 1,500
South Asian	~43k	1 in 140	1 in 770
Remaining (unassigned)	~30k	1 in 150	1 in 1,800
European (Finnish)	~27k	1 in 680	1 in 1,600
Admixed American	~22k	1 in 110	1 in 1,300
African / African American	~21k	1 in 210	1 in 1,400
East Asian	~20k	1 in 200	1 in 600
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.