INSL6

protein-coding

insulin like 6

Gene summary

The protein encoded by this gene contains a classical signature of the insulin superfamily and is significantly similar to relaxin and relaxin-like factor. This gene is preferentially expressed in testis. Its expression in testis is restricted to interstitial cells surrounding seminiferous tubules, which suggests a role in sperm development and fertilization. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007179.3

Inheritance

—

ClinVar variants

U:53B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.43

Max pathogenic AF

—

Genomic locus

chr9:5,123,880-5,185,647

External References & Databases

Ensembl (ENSG00000120210)

Transcript & Mutation Effects

hg38 • Region Span ~61.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INSL6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007179.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			51 clinvar	1 clinvar	1 clinvar	53
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	0	0	53	3	2	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007179.3	RefSeq	NP_009110.2	2	MANE Select
ENST00000381641.4	Ensembl	ENSP00000371054.3	2	MANE Select
ENST00000649639.1	Ensembl	ENSP00000497955.1	3	Standard
ENST00000649639.2	Ensembl	ENSP00000497955.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
regulation of signaling receptor activity

Molecular Function

hormone activity

Cellular Component

cellular_component
extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381641
Coding exons: 2
Length: 53690
Individuals with no LoFs: 125401
Homozygous LoFs: 2
Heterozygous LoFs: 257
Defined: 125660
p: 0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.45	201	124	1.62	0.00000784	1364
Missense (PolyPhen)		39	27.522	1.4171		307
Synonymous	-3.20	75	47.1	1.59	0.00000298	405
Loss of Function	-1.11	11	7.67	1.43	3.26e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.0058	0.0056	notable
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.00014	0.00013	rare
Other	0.00067	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May have a role in sperm development and fertilization.;

Recessive Scores

pRec: 0.0846

Intolerance Scores

LoFtool: 0.408
RVIS EVS: 0.55
RVIS percentile EVS: 81.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00211

Gene Damage Prediction

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