PDE4DIP

Chr 1

phosphodiesterase 4D interacting protein

Also known as: CMYA2, MMGL

NCBI Gene: 9659 ENSG00000178104 UniProt: Q5VU43 OMIM: 608117

The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.82

Clinical Summary— PDE4DIP

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 2 VUS of 151 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 3.13

OE 0.68 (0.56–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.40Z-score

OE missense 1.12 (1.07–1.18)

1136 obs / 1010.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.68 (0.56–0.82)

0≤0.351.4

Missense OE?1.12 (1.07–1.18)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 76 / 111.7Missense obs/exp: 1136 / 1010.5Syn Z: 0.27

This gene — mechanism propensity

0.77top 25%

GOF

0.6444th %ile

LOF

0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS2

Likely Benign15

Benign7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	2	0	0	2
VUS	0	1	0	1	2
Likely Benign	0	1	0	14	15
Benign	3	3	1	0	7
Total	3	8	1	15	27

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

View in ClinVar →

73 pathogenic / likely-pathogenic (of 98) ClinVar copy-number / structural variants overlap PDE4DIP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →