INSL4

protein-coding

insulin like 4

Gene summary

INSL4 encodes the insulin-like 4 protein, a member of the insulin superfamily. INSL4 encodes a precursor that undergoes post-translational cleavage to produce 3 polypeptide chains, A-C, that form tertiary structures composed of either all three chains, or just the A and B chains. Expression of INSL4 products occurs within the early placental cytotrophoblast and syncytiotrophoblast. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002195.2

Inheritance

—

ClinVar variants

U:34B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.51

Max pathogenic AF

—

Genomic locus

chr9:5,231,419-5,235,304

External References & Databases

Ensembl (ENSG00000120211)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 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 INSL4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002195.2. 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
missense			34 clinvar	4 clinvar	1 clinvar	39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	34	4	2	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002195.2	RefSeq	NP_002186.1	2	MANE Select
ENST00000239316.4	Ensembl	ENSP00000239316.4	2	MANE Select
ENST00001094357.1	Ensembl	ENSP00000764163.1	3	Standard
ENST00001094358.1	Ensembl	ENSP00000764164.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

signal transduction
cell-cell signaling
multicellular organism development
female pregnancy
cell population proliferation

Molecular Function

signaling receptor binding
insulin-like growth factor receptor binding
hormone activity

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000239316
Coding exons: 2
Length: 3886
Individuals with no LoFs: 125388
Homozygous LoFs: 1
Heterozygous LoFs: 16
Defined: 125405
p: 0.0000678

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.43	112	76.7	1.46	0.00000413	870
Missense (PolyPhen)		23	12.86	1.7885		159
Synonymous	-0.213	32	30.5	1.05	0.00000148	295
Loss of Function	-0.856	5	3.32	1.51	2.26e-7	33

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000026	rare
South Asian	0.00043	0.00042	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in trophoblast development and in the regulation of bone formation.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.551
RVIS EVS: 0.71
RVIS percentile EVS: 85.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0962

Gene Damage Prediction

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