FNDC8

Summary

FNDC8 (fibronectin type III domain containing 8, HGNC:25286) is a protein-coding gene on chromosome 17q12, encoding Fibronectin type III domain-containing protein 8 (Q8TC99).

Located in nucleus.

Source: NCBI Gene 54752 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_017559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25286
Approved symbol	FNDC8
Name	fibronectin type III domain containing 8
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434H2215
Ensembl gene	ENSG00000073598
Ensembl biotype	protein_coding
Entrez	54752

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000158009

RefSeq mRNA: 1 — MANE Select: NM_017559 NM_017559

CCDS: CCDS11290

Canonical transcript exons

ENST00000158009 — 4 exons

Exon	Start	End
ENSE00000714180	35127042	35127417
ENSE00000714182	35129422	35129658
ENSE00001160547	35130282	35130732
ENSE00001160550	35121615	35121902

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 94.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2850 / max 298.6183, expressed in 4 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160336	0.2356	4
160334	0.0281	3
160335	0.0213	3

Top tissues by expression

212 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.08	gold quality
right testis	UBERON:0004534	94.08	gold quality
testis	UBERON:0000473	90.80	gold quality
sperm	CL:0000019	85.02	gold quality
male germ cell	CL:0000015	84.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.75	gold quality
adult organism	UBERON:0007023	75.76	gold quality
pancreatic ductal cell	CL:0002079	75.73	silver quality
triceps brachii	UBERON:0001509	75.32	gold quality
gluteal muscle	UBERON:0002000	73.50	gold quality
vastus lateralis	UBERON:0001379	72.48	gold quality
olfactory bulb	UBERON:0002264	71.72	gold quality
type B pancreatic cell	CL:0000169	71.61	gold quality
quadriceps femoris	UBERON:0001377	71.57	gold quality
tongue squamous epithelium	UBERON:0006919	71.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.01	gold quality
diaphragm	UBERON:0001103	65.86	gold quality
biceps brachii	UBERON:0001507	65.19	gold quality
vena cava	UBERON:0004087	64.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	64.48	gold quality
deltoid	UBERON:0001476	63.75	gold quality
left ventricle myocardium	UBERON:0006566	63.69	gold quality
heart right ventricle	UBERON:0002080	62.74	gold quality
CA1 field of hippocampus	UBERON:0003881	62.03	gold quality
thymus	UBERON:0002370	62.02	gold quality
layer of synovial tissue	UBERON:0007616	61.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	60.80	gold quality
substantia nigra pars compacta	UBERON:0001965	60.74	gold quality
inferior olivary complex	UBERON:0002127	60.56	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	60.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.21
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting FNDC8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-5194	96.77	63.91	1021

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fndc8	ENSMUSG00000018844
rattus_norvegicus	Fndc8	ENSRNOG00000008264

Protein

Protein identifiers

Fibronectin type III domain-containing protein 8 — Q8TC99 (reviewed: Q8TC99)

All UniProt accessions (1): Q8TC99

RefSeq proteins (1): NP_060029* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily

Pfam: PF00041

UniProt features (4 total): sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC99-F1	60.64	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, XU_GH1_AUTOCRINE_TARGETS_UP, CAGCTG_AP4_Q5, SCGGAAGY_ELK1_02, CACTGCC_MIR34A_MIR34C_MIR449, MIKKELSEN_MEF_LCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_D, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, ZWANG_DOWN_BY_2ND_EGF_PULSE, SRC_UP.V1_UP, KRAS.300_UP.V1_UP, KRAS.600_UP.V1_UP, KRAS.600.LUNG.BREAST_UP.V1_UP, KRAS.LUNG_UP.V1_UP, KRAS.LUNG.BREAST_UP.V1_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNDC8	SCP2D1	Q9UJQ7	665
FNDC8	SYNGR4	O95473	606
FNDC8	MGAT4D	A6NG13	598
FNDC8	GLB1L	Q6UWU2	576
FNDC8	FSCN3	Q9NQT6	541
FNDC8	TMEM202	A6NGA9	480
FNDC8	FAM221B	A6H8Z2	478
FNDC8	SLC36A3	Q495N2	461
FNDC8	HMGB4	Q8WW32	432
FNDC8	PRM1	P04553	418
FNDC8	TEX13A	Q9BXU3	417
FNDC8	MAMLD1	Q13495	399
FNDC8	USP26	Q9BXU7	376
FNDC8	MORN3	Q6PF18	369
FNDC8	BPIFA3	Q9BQP9	355

IntAct

21 interactions, top by confidence:

A	B	Type	Score
MAD2L1BP	FNDC8	psi-mi:“MI:0915”(physical association)	0.670
SMCO1	FNDC8	psi-mi:“MI:0915”(physical association)	0.560
	FNDC8	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	FNDC8	psi-mi:“MI:0915”(physical association)	0.560
FNDC8	PIK3R3	psi-mi:“MI:0915”(physical association)	0.560
FNDC8	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
FNDC8	ZNF609	psi-mi:“MI:0914”(association)	0.350
SPARCL1	DUSP14	psi-mi:“MI:0914”(association)	0.350
MAD2L1BP	FNDC8	psi-mi:“MI:0915”(physical association)	0.000
SMCO1	FNDC8	psi-mi:“MI:0915”(physical association)	0.000
	FNDC8	psi-mi:“MI:0915”(physical association)	0.000
ZNF76	FNDC8	psi-mi:“MI:0915”(physical association)	0.000
PIK3R3	FNDC8	psi-mi:“MI:0915”(physical association)	0.000
MCRS1	FNDC8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): FNDC8 (Two-hybrid), PIK3R3 (Two-hybrid), MAD2L1BP (Two-hybrid), MCRS1 (Two-hybrid), SMCO1 (Two-hybrid), MBLAC1 (Two-hybrid), KLHL24 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), ZNF609 (Affinity Capture-MS), FNDC8 (Affinity Capture-MS), METTL18 (Affinity Capture-MS), SP3 (Affinity Capture-MS), EIF2AK2 (Affinity Capture-MS), DCP2 (Affinity Capture-MS), PTS (Affinity Capture-MS)

ESM2 similar proteins: A2CI98, A6NMN3, A7MBB4, B2RXB0, B4F6Q9, D3YV92, F1M5M3, F1MJR8, O43283, P15304, P56645, Q14CH0, Q1HKZ5, Q28F43, Q2KIP3, Q2NKQ1, Q2PFD7, Q2YDH8, Q3UPF5, Q3UZD7, Q3V1D5, Q4G017, Q4R767, Q5R7R7, Q5R8X7, Q5RA75, Q5RJN7, Q5SW75, Q61194, Q68FV5, Q6NRK3, Q6NXP2, Q6P995, Q75NT5, Q76I76, Q7M6U3, Q80TM9, Q8BPQ7, Q8BQU7, Q8CCC3

Diamond homologs: Q2YDH8, Q4R767, Q8TC99, Q9D2H8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

63 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

459 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35121898:CTACT:C	donor_gain	1.0000
17:35121900:ACT:A	donor_gain	1.0000
17:35121903:G:GG	donor_gain	1.0000
17:35127034:T:TA	acceptor_gain	1.0000
17:35127037:TCCA:T	acceptor_loss	1.0000
17:35127038:CCA:C	acceptor_loss	1.0000
17:35127040:A:AG	acceptor_gain	1.0000
17:35127040:AG:A	acceptor_gain	1.0000
17:35127041:G:GG	acceptor_gain	1.0000
17:35127041:GG:G	acceptor_gain	1.0000
17:35127041:GGA:G	acceptor_gain	1.0000
17:35127041:GGAA:G	acceptor_gain	1.0000
17:35127413:C:G	donor_gain	1.0000
17:35127415:GTG:G	donor_gain	1.0000
17:35127415:GTGGT:G	donor_loss	1.0000
17:35127416:TGGTG:T	donor_loss	1.0000
17:35127417:GGT:G	donor_loss	1.0000
17:35127418:G:GG	donor_gain	1.0000
17:35127418:GTG:G	donor_loss	1.0000
17:35127419:TGCG:T	donor_loss	1.0000
17:35129569:C:G	donor_gain	1.0000
17:35129575:GAGC:G	donor_gain	1.0000
17:35129578:C:G	donor_gain	1.0000
17:35129606:GT:G	donor_gain	1.0000
17:35129659:G:GG	donor_gain	1.0000
17:35130278:TCA:T	acceptor_loss	1.0000
17:35130279:CAGT:C	acceptor_loss	1.0000
17:35130280:A:AG	acceptor_gain	1.0000
17:35130280:AGT:A	acceptor_loss	1.0000
17:35130281:G:A	acceptor_loss	1.0000

AlphaMissense

2126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35129428:T:A	W198R	0.996
17:35129428:T:C	W198R	0.996
17:35129612:G:C	R259P	0.995
17:35127413:C:A	A194D	0.993
17:35129609:T:A	V258D	0.993
17:35129641:T:A	W269R	0.993
17:35129641:T:C	W269R	0.993
17:35130283:T:C	F275S	0.992
17:35129430:G:C	W198C	0.991
17:35129430:G:T	W198C	0.991
17:35129643:G:C	W269C	0.988
17:35129643:G:T	W269C	0.988
17:35130282:T:C	F275L	0.988
17:35130284:T:A	F275L	0.988
17:35130284:T:G	F275L	0.988
17:35129579:T:C	L248P	0.987
17:35127412:G:C	A194P	0.986
17:35129429:G:C	W198S	0.986
17:35129570:T:C	L245P	0.984
17:35129564:T:A	V243D	0.983
17:35127377:C:A	P182H	0.982
17:35129423:T:A	I196N	0.981
17:35129464:T:G	Y210D	0.981
17:35130283:T:G	F275C	0.981
17:35129596:T:G	Y254D	0.979
17:35129471:T:C	L212P	0.978
17:35129635:G:T	G267W	0.977
17:35129636:G:T	G267V	0.977
17:35129423:T:G	I196S	0.976
17:35129477:T:C	L214S	0.976

dbSNP variants (sampled 300 via entrez): RS1000021705 (17:35123075 G>A), RS1000053048 (17:35122632 C>G), RS1000163855 (17:35130645 G>A), RS1000369254 (17:35124788 C>G,T), RS1000425693 (17:35130934 C>G,T), RS1000677557 (17:35123609 G>A), RS1001110921 (17:35123371 G>A), RS1001509744 (17:35128113 G>A), RS1002022743 (17:35127825 G>A), RS1002383568 (17:35121470 G>A), RS1002440909 (17:35128469 C>T), RS1002684549 (17:35120476 A>G), RS1003128646 (17:35120269 T>G), RS1003513514 (17:35125087 A>G), RS1004034235 (17:35124786 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614291

GenCC curated gene-disease

Mondo (1): breast-ovarian cancer, familial, susceptibility to, 4 (MONDO:0013669)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
N-(1-naphthyl)ethylenediamine	affects response to substance	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.