INSL3

insulin like 3, the group of Receptor ligands

Basic information

Region (hg38): 19:17816511-17821574

Previous symbols: [ "RLNL" ]

Links

ENSG00000248099 ∙ NCBI:3640 ∙ OMIM:146738 ∙ HGNC:6086 ∙ Uniprot:P51460 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cryptorchidism (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cryptorchidism	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	11095425; 12601553; 12970298; 17028442; 17437853; 19416190

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INSL3 gene.

• Inborn genetic diseases (14 variants)
• not provided (7 variants)
• Cryptorchidism (4 variants)
• not specified (2 variants)
• Bilateral cryptorchidism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INSL3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			15	1	2	18
nonsense						0
start loss						0
frameshift		2				2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	2	15	1	6

Highest pathogenic variant AF is 0.0000657

Variants in INSL3

This is a list of pathogenic ClinVar variants found in the INSL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-17816591-C-T			Benign (Nov 12, 2018)
19-17816870-G-A		Inborn genetic diseases	Uncertain significance (May 18, 2022)
19-17816870-G-C			Uncertain significance (-)
19-17816920-G-C		Cryptorchidism	Pathogenic (Jan 01, 2003)
19-17816939-T-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
19-17816945-C-T		Cryptorchidism • not specified	Uncertain significance (May 04, 2022)
19-17816946-G-A		Cryptorchidism	Pathogenic (Sep 01, 2003)
19-17816972-G-A		Cryptorchidism	Pathogenic (Sep 01, 2003)
19-17817006-C-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
19-17817006-C-T		Inborn genetic diseases	Likely benign (Sep 14, 2023)
19-17817018-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
19-17817032-C-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
19-17817033-G-A		Cryptorchidism	Pathogenic (Nov 01, 2000)
19-17817039-C-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
19-17817050-A-G		Inborn genetic diseases	Uncertain significance (Jan 18, 2023)
19-17817059-C-A		Cryptorchidism • Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
19-17817059-C-G		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
19-17817089-G-A			Benign (Jun 20, 2021)
19-17821329-T-C		Cryptorchidism	Benign (Aug 19, 2021)
19-17821348-G-C		INSL3-related disorder	Likely benign (Mar 20, 2019)
19-17821358-C-CG		Inborn genetic diseases	Likely pathogenic (Apr 03, 2017)
19-17821363-G-GC		Bilateral cryptorchidism	Likely pathogenic (Jan 12, 2023)
19-17821381-T-C		Cryptorchidism	Benign (Aug 19, 2021)
19-17821392-C-G		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
19-17821392-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INSL3	protein_coding	protein_coding	ENST00000379695	3	5063

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0158	0.714	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.508	76	89.5	0.849	0.00000603	979
Missense in Polyphen		28	34.136	0.82024		307
Synonymous	-0.0303	42	41.8	1.01	0.00000337	341
Loss of Function	0.685	3	4.58	0.655	3.81e-7	40

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);MET in type 1 papillary renal cell carcinoma;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Relaxin receptors;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.113

Haploinsufficiency Scores

• pHI: 0.537
• hipred: N
• hipred_score: 0.146
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Insl3
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype; skeleton phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;cell-cell signaling;spermatogenesis;regulation of signaling receptor activity;positive regulation of epithelial cell migration;positive regulation of wound healing
• Cellular component: extracellular region;extracellular space
• Molecular function: G protein-coupled receptor binding;protease binding;signaling receptor binding;insulin receptor binding;hormone activity