WIPF3

Chr 7

WAS/WASL interacting protein family member 3

Also known as: CR16

NCBI Gene: 644150ENSG00000122574UniProt: A6NGB9

Predicted to enable alpha-tubulin binding activity and gamma-tubulin binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation; endosomal transport; and exocytosis. Predicted to be located in cytosol. Predicted to be part of WASH complex. Predicted to be active in early endosome; recycling endosome; and synapse. [provided by Alliance of Genome Resources, Jul 2025]

122
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— WIPF3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 92 VUS of 122 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.
0.81LOEUF
pLI 0.002
Z-score 2.13
OE 0.43 (0.24–0.81)
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.
-0.33Z-score
OE missense 1.06 (0.96–1.17)
272 obs / 257.1 exp
Tolerant

Tolerant to missense variation

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.0.43 (0.24–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.96–1.17)
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.1.08
0≤1.21.6
LoF obs/exp: 7 / 16.3Missense obs/exp: 272 / 257.1Syn Z: -0.62

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic4
VUS92
Likely Benign4
Benign2
20
Pathogenic
4
Likely Pathogenic
92
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
4
0
4
VUS
0
88
4
0
92
Likely Benign
0
4
0
0
4
Benign
0
1
0
1
2
Total093281122

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

View in ClinVar →

Protein Context — Lollipop Plot

WIPF3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Glucocorticoids, genes and brain function.
Juszczak GR et al.·Prog Neuropsychopharmacol Biol Psychiatry
2018Review
Identification of ARMH4 and WIPF3 as human podocyte proteins with potential roles in immunomodulation and cytoskeletal dynamics.
De Luca F et al.·PLoS One
2023
Identification of shared mechanisms between Alzheimer's disease and atherosclerosis by integrated bioinformatics analysis.
Wang J et al.·Eur J Med Res
2025Functional
Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients.
Hammoudeh SM et al.·Front Immunol
2021Cohort
[Testicular CR16 and spermatogenesis].
Fu XC et al.·Zhonghua Nan Ke Xue
2012Review
CR16 forms a complex with N-WASP in human testes.
Xiang W et al.·Cell Tissue Res
2011
Mammalian verprolin CR16 acts as a modulator of ITSN scaffold proteins association with actin.
Kropyvko S et al.·Biochem Biophys Res Commun
2017
CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family.
Ho HY et al.·Proc Natl Acad Sci U S A
2001
In vitro reconstitution of cdc42-mediated actin assembly using purified components.
Ho HY et al.·Methods Enzymol
2006
Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.
Ho HY et al.·Cell
2004
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