DIAPH2

Chr XXLD

diaphanous related formin 2

Also known as: DIA, DIA2, DRF2, POF, POF2, POF2A

NCBI Gene: 1730ENSG00000147202UniProt: O60879

This gene encodes a formin family protein that regulates actin cytoskeleton dynamics and endosome motility, and may function in oogenesis. Mutations cause premature ovarian failure 2A with X-linked dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.28), suggesting intolerance to protein disruption.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Premature ovarian failure 2AMIM #300511
XLD
0
Active trials
3
Pubs (1 yr)
27
P/LP submissions
0%
P/LP missense
0.28
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— DIAPH2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 105 VUS of 310 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.994
Z-score 5.14
OE 0.14 (0.08–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.83Z-score
OE missense 0.73 (0.66–0.81)
261 obs / 358.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.08–0.28)
0≤0.351.4
Missense OE0.73 (0.66–0.81)
0≤0.61.4
Synonymous OE1.15
0≤1.21.6
LoF obs/exp: 6 / 41.9Missense obs/exp: 261 / 358.7Syn Z: -1.33

ClinVar Variant Classifications

310 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
VUS105
Likely Benign17
Benign2
25
Pathogenic
105
VUS
17
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
0
0
0
VUS
1
93
11
0
105
Likely Benign
0
8
4
5
17
Benign
0
0
2
0
2
Total1101425149

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

View in ClinVar →

Protein Context — Lollipop Plot

DIAPH2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients