FNDC5

protein-coding

fibronectin type III domain containing 5, the group of Fibronectin type III domain containing

Gene summary

This gene encodes a secreted protein that is released from muscle cells during exercise. The encoded protein may participate in the development of brown fat. Translation of the precursor protein initiates at a non-AUG start codon at a position that is conserved as an AUG start codon in other organisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

MANE transcript

N/A

Inheritance

—

ClinVar variants

U:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:32,862,268-32,872,482

External References & Databases

Ensembl (ENSG00000160097)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 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 FNDC5 variants in ClinVar

0 Conditions Cataloged

No annotated ClinVar phenotypes.

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . 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						0
missense			11 clinvar			11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	0	0	11

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
ENST00000373471.10	Ensembl	ENSP00000362570.6	6	MANE Select
ENST00000373471.9	Ensembl	ENSP00000362570.5	6	MANE Select
NM_001171940.2	RefSeq	NP_001165411.2	6	Standard
NM_001171941.3	RefSeq	NP_001165412.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
regulation of signaling receptor activity
response to muscle activity
positive regulation of brown fat cell differentiation

Molecular Function

molecular_function
hormone activity

Cellular Component

extracellular region
peroxisomal membrane
endoplasmic reticulum
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000609187
Coding exons: 4
Length: 10215
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125746
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.603	73	89.0	0.820	0.00000543	907
Missense (PolyPhen)		32	42.165	0.75893		408
Synonymous	0.854	28	34.4	0.815	0.00000215	256
Loss of Function	2.00	1	6.53	0.153	2.77e-7	76

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue. {ECO:0000269|PubMed:24040023}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.224
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.330

Gene Damage Prediction

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