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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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INSL6
insulin like 6
Chromosome 9 · 9p24.1
NCBI Gene: 11172Ensembl: ENSG00000120210.8HGNC: HGNC:6089UniProt: Q9Y581
9PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Swiss-Prot Reviewed
hormone activitysignal transductionextracellular regionpolycythemia veraulcerative colitisfood allergymyeloproliferative disorder
✦AI Summary

INSL6 (insulin-like 6) is a secreted peptide hormone belonging to the insulin/relaxin superfamily with primary roles in male reproductive physiology and tissue protection. INSL6 is predominantly expressed in meiotic and postmeiotic germ cells of the testis, specifically in spermatocytes and round spermatids 1. The protein is synthesized as a ~28 kDa precursor and undergoes posttranslational processing by furin protease and other mechanisms to generate an ~8 kDa mature form, with modifications including disulfide bonds, glycosylation, and ubiquitination 2. Mechanistically, INSL6 is essential for spermatogenesis progression; INSL6-deficient mice exhibit impaired fertility with arrested germ cell development at late meiotic prophase, reduced sperm motility, and increased germ cell apoptosis 3. Beyond reproduction, INSL6 functions as an injury-induced myokine with immunomodulatory properties—muscle-specific overexpression protects against autoimmune myositis through reduced lymphocyte infiltration and inflammatory cytokine expression 4. INSL6 also exhibits cardioprotective effects; genetic loss-of-function increases cardiac dysfunction and fibrosis in heart failure models, while recombinant INSL6 administration attenuates fibrosis and systolic dysfunction 5. Clinically, INSL6 expression is reduced in dermatomyositis and polymyositis patients and may serve as a prognostic biomarker in breast cancer 6. These findings suggest INSL6 has therapeutic potential for reproductive, autoimmune, and cardiovascular disorders.

Sources cited
1
INSL6 is expressed in meiotic and postmeiotic germ cells, is a secreted protein synthesized as ~28 kDa precursor processed to ~8 kDa mature form, and undergoes furin-dependent cleavage and multiple posttranslational modifications
PMID: 16935843
2
INSL6 is a member of the insulin family expressed at high levels in testis specifically within seminiferous tubules in spermatocytes and round spermatids
PMID: 10819760
3
INSL6-deficient mice exhibit impaired fertility with arrested spermatogenesis at late meiotic prophase, reduced sperm count and motility, and increased germ cell apoptosis
PMID: 19520787
4
INSL6 is an injury-induced myokine that protects against experimental autoimmune myositis through reduced lymphocyte infiltration and inflammatory cytokine expression
PMID: 25161767
5
INSL6 inhibits cardiac systolic dysfunction and fibrosis in heart failure models; INSL6-knockout mice show greater cardiac dysfunction and fibrosis
PMID: 29887522
6
INSL6 expression is reduced in multiple cancers including breast cancer and serves as a potential diagnostic and prognostic biomarker
PMID: 36798786
7
INSL6 is a major product of male germ cells; INSL6 gene disruption in mice leads to disruption of spermatogenesis
PMID: 27933606
8
INSL6 is involved in maintenance of adequate spermatogenesis and represents a neohormone with potential use as a biomarker of reproductive health
PMID: 23337591
Disease Associationsⓘ20
polycythemia veraOpen Targets
0.33Weak
ulcerative colitisOpen Targets
0.32Weak
food allergyOpen Targets
0.27Weak
myeloproliferative disorderOpen Targets
0.23Weak
inflammatory bowel diseaseOpen Targets
0.22Weak
blood diseaseOpen Targets
0.20Weak
insomniaOpen Targets
0.18Weak
hepatic vein thrombosisOpen Targets
0.18Weak
asthmaOpen Targets
0.18Weak
chronic myeloproliferative disorderOpen Targets
0.16Weak
thrombocythemia 3Open Targets
0.15Weak
allergic rhinitisOpen Targets
0.14Weak
genetic disorderOpen Targets
0.12Weak
respiratory system diseaseOpen Targets
0.10Weak
azoospermiaOpen Targets
0.10Weak
cervical carcinomaOpen Targets
0.09Suggestive
hematologic diseaseOpen Targets
0.09Suggestive
myelodysplastic syndromeOpen Targets
0.09Suggestive
clonal hematopoiesisOpen Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
INSL3Protein interaction98%INSL4Protein interaction98%TCEAL9Protein interaction77%INSL5Protein interaction74%RLN3Protein interaction72%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
15%
Ovary
8%
Lung
8%
Liver
5%
Brain
2%
Gene Interaction Network
Click a node to explore
INSL6INSL3INSL4TCEAL9INSL5RLN3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9Y581
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.61 [1.07–1.94]
RankingsWhere INSL6 stands among ~20K protein-coding genes
  • #17,349of 20,598
    Most Researched9
  • #17,630of 17,882
    Most Constrained (LOEUF)1.94
Genes detectedINSL6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Insulin-like peptide 6: characterization of secretory status and posttranslational modifications.
PMID: 16935843
Endocrinology · 2006
1.00
2
Identification of INSL6, a new member of the insulin family that is expressed in the testis of the human and rat.
PMID: 10819760
Biol Reprod · 2000
0.90
3
Relaxin-like peptides in male reproduction - a human perspective.
PMID: 27933606
Br J Pharmacol · 2017
0.80
4
The injury-induced myokine insulin-like 6 is protective in experimental autoimmune myositis.
PMID: 25161767
Skelet Muscle · 2014
0.70
5
Inactivation of insulin-like factor 6 disrupts the progression of spermatogenesis at late meiotic prophase.
PMID: 19520787
Endocrinology · 2009
0.60