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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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WFIKKN1
WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 1
Chromosome 16 · 16p13.3
NCBI Gene: 117166Ensembl: ENSG00000127578.7HGNC: HGNC:30912UniProt: Q96NZ8
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of transforming growth factor beta receptor signaling pathwayprotein bindingreceptor antagonist activitytransforming growth factor beta bindingneurodegenerative diseasespondylometaphyseal dysplasia, A4 typeRichieri Costa-da Silva syndromePoland syndrome
✦AI Summary

WFIKKN1 is a multidomain extracellular protein containing WAP, follistatin, immunoglobulin, Kunitz-type protease inhibitor, and NTR domains that functions as a growth factor antagonist and binding protein 1. The protein binds with high affinity to growth and differentiation factors GDF8 (myostatin) and GDF11, serving as a potent antagonist that inhibits their biological activity in the nanomolar range 23. Structure-function studies reveal that the follistatin domain primarily mediates binding to mature growth factors, while the NTR domain contributes significantly to interactions with myostatin propeptide 2. WFIKKN1 also binds TGFβ1, BMP2, and BMP4 with high affinity but does not inhibit their signaling activity, suggesting it functions as a growth factor binding protein for these factors, potentially localizing their action and establishing growth factor gradients 3. The protein enhances BMP1-mediated activation of latent myostatin, likely by facilitating conformational changes that make cleavage sites more accessible 4. WFIKKN1 appears to function as a 'companion' protein that regulates TGFB activity by providing localized and sustained presentation of growth factors to their receptors 5. In zebrafish, WFIKKN1 is involved in AHR signaling and influences transcriptome, proteome, and behavioral development 6.

Sources cited
1
WFIKKN1 is a multidomain protein with WAP, follistatin, immunoglobulin, Kunitz protease inhibitor, and NTR domains that binds myostatin and GDF11 with high affinity
PMID: 21936825
2
WFIKKN1 binds GDF8/myostatin and GDF11 with high affinity, with follistatin domain responsible for mature growth factor binding and NTR domain for propeptide interaction
PMID: 18596030
3
WFIKKN1 inhibits GDF8 and GDF11 activity in nanomolar range but binds TGFβ1, BMP2, BMP4 without inhibiting their activity, functioning as binding protein
PMID: 21054789
4
WFIKKN1 enhances BMP1-mediated activation of latent myostatin, likely through conformational changes
PMID: 27782377
5
WFIKKN proteins function as 'companion' proteins regulating TGFB activity by providing localized growth factor presentation
PMID: 27325460
6
In zebrafish, WFIKKN1 is involved in AHR signaling and influences transcriptome, proteome, and behavior
PMID: 35377459
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.31Weak
spondylometaphyseal dysplasia, A4 typeOpen Targets
0.04Suggestive
Richieri Costa-da Silva syndromeOpen Targets
0.04Suggestive
Poland syndromeOpen Targets
0.04Suggestive
autosomal recessive spondylocostal dysostosisOpen Targets
0.04Suggestive
spondylocostal dysostosis 5Open Targets
0.04Suggestive
kyphomelic dysplasiaOpen Targets
0.03Suggestive
spondylocostal dysostosis 2, autosomal recessiveOpen Targets
0.03Suggestive
thoracolaryngopelvic dysplasiaOpen Targets
0.03Suggestive
Becker nevus syndromeOpen Targets
0.03Suggestive
Metaphyseal chondrodysplasia, Schmid typeOpen Targets
0.03Suggestive
Schmid metaphyseal chondrodysplasiaOpen Targets
0.03Suggestive
mesomelic dysplasia, Kantaputra typeOpen Targets
0.03Suggestive
metatropic dysplasiaOpen Targets
0.03Suggestive
short-rib thoracic dysplasia 17 with or without polydactylyOpen Targets
0.03Suggestive
autosomal dominant osteosclerosis, Worth typeOpen Targets
0.03Suggestive
spondylocostal dysostosis 1, autosomal recessiveOpen Targets
0.03Suggestive
Heart defects - limb shorteningOpen Targets
0.03Suggestive
heart defects-limb shortening syndromeOpen Targets
0.03Suggestive
esophageal diseaseOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MSTNProtein interaction88%GDF11Protein interaction88%NTSR1Protein interaction88%WFIKKN2Shared pathway80%FSTProtein interaction71%LRRC32Shared pathway67%
Tissue Expression6 tissues
Ovary
100%
Liver
84%
Lung
52%
Brain
31%
Bone Marrow
30%
Heart
5%
Gene Interaction Network
Click a node to explore
WFIKKN1MSTNGDF11NTSR1WFIKKN2FSTLRRC32
PROTEIN STRUCTURE
Preparing viewer…
PDB2DDI · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.58 [0.86–1.94]
RankingsWhere WFIKKN1 stands among ~20K protein-coding genes
  • #14,869of 20,598
    Most Researched18
  • #17,589of 17,882
    Most Constrained (LOEUF)1.94
Genes detectedWFIKKN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior.
PMID: 35377459
Toxicol Sci · 2022
1.00
2
WFIKKN1 and WFIKKN2: "Companion" proteins regulating TGFB activity.
PMID: 27325460
Cytokine Growth Factor Rev · 2016
0.90
3
Biological functions of the WAP domain-containing multidomain proteins WFIKKN1 and WFIKKN2.
PMID: 21936825
Biochem Soc Trans · 2011
0.80
4
Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11.
PMID: 18596030
J Biol Chem · 2008
0.70
5
WFIKKN1 and WFIKKN2 bind growth factors TGFβ1, BMP2 and BMP4 but do not inhibit their signalling activity.
PMID: 21054789
FEBS J · 2010
0.60