INSL6

Chr 9

insulin like 6

Also known as: RIF1

NCBI Gene: 11172ENSG00000120210UniProt: Q9Y581OMIM: 606414

The protein encoded by INSL6 belongs to the insulin superfamily and may function in sperm development and fertilization, with expression restricted to testicular interstitial cells. Mutations in INSL6 cause autosomal recessive cryptorchidism with or without insulin-like factor 6 deficiency, affecting male reproductive development. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.92
Clinical Summary— INSL6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 161 VUS of 300 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
1.92LOEUF
pLI 0.000
Z-score -1.11
OE 1.43 (0.88–1.92)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.45Z-score
OE missense 1.62 (1.44–1.82)
201 obs / 124.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.43 (0.88–1.92)
0≤0.351.4
Missense OE1.62 (1.44–1.82)
0≤0.61.4
Synonymous OE1.59
0≤1.21.6
LoF obs/exp: 11 / 7.7Missense obs/exp: 201 / 124.1Syn Z: -3.20
DN
0.79top 25%
GOF
0.2895th %ile
LOF
0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic1
VUS161
Likely Benign54
Benign28
Conflicting7
30
Pathogenic
1
Likely Pathogenic
161
VUS
54
Likely Benign
28
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
1
0
0
1
VUS
3
148
10
0
161
Likely Benign
1
7
18
28
54
Benign
0
1
22
5
28
Conflicting
—7
Total41578033281

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

View in ClinVar →

Protein Context — Lollipop Plot

INSL6 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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 3 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