FSIP1

Summary

FSIP1 (fibrous sheath interacting protein 1, HGNC:21674) is a protein-coding gene on chromosome 15q14, encoding Fibrous sheath-interacting protein 1 (Q8NA03).

Predicted to act upstream of or within several processes, including axoneme assembly; homeostasis of number of cells within a tissue; and vesicle organization. Predicted to be active in acrosomal vesicle; nucleus; and sperm head.

Source: NCBI Gene 161835 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 102 total — 1 pathogenic
• MANE Select transcript: NM_152597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21674
Approved symbol	FSIP1
Name	fibrous sheath interacting protein 1
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35989
Ensembl gene	ENSG00000150667
Ensembl biotype	protein_coding
OMIM	615795
Entrez	161835

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000350221, ENST00000559547, ENST00000559692, ENST00000560769, ENST00000642527, ENST00000884360, ENST00000884361, ENST00000942556

RefSeq mRNA: 2 — MANE Select: NM_152597 NM_001324338, NM_152597

CCDS: CCDS10050

Canonical transcript exons

ENST00000350221 — 12 exons

Exon	Start	End
ENSE00000995830	39738091	39738201
ENSE00000995831	39765592	39765746
ENSE00000995832	39763821	39763914
ENSE00000995834	39770427	39770610
ENSE00000995836	39726589	39726747
ENSE00001099539	39617735	39618245
ENSE00001099540	39713444	39713581
ENSE00001283324	39782628	39782841
ENSE00001283336	39600031	39600926
ENSE00003532610	39739665	39739789
ENSE00003574039	39776399	39776531
ENSE00003614079	39741805	39741900

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 93.66.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0781 / max 43.0608, expressed in 557 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149457	0.8946	440
149451	0.1161	54
149452	0.0674	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.66	gold quality
rectum	UBERON:0001052	85.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.14	gold quality
transverse colon	UBERON:0001157	78.22	gold quality
right testis	UBERON:0004534	73.75	gold quality
sperm	CL:0000019	73.02	gold quality
left testis	UBERON:0004533	72.96	gold quality
cortical plate	UBERON:0005343	72.16	gold quality
testis	UBERON:0000473	71.74	gold quality
stromal cell of endometrium	CL:0002255	70.86	gold quality
ventricular zone	UBERON:0003053	69.51	gold quality
lower esophagus mucosa	UBERON:0035834	69.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.41	gold quality
ganglionic eminence	UBERON:0004023	65.55	gold quality
right uterine tube	UBERON:0001302	65.49	gold quality
colon	UBERON:0001155	65.03	gold quality
smooth muscle tissue	UBERON:0001135	64.84	gold quality
large intestine	UBERON:0000059	64.49	gold quality
bronchial epithelial cell	CL:0002328	64.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.83	gold quality
adenohypophysis	UBERON:0002196	62.99	gold quality
bronchus	UBERON:0002185	62.98	gold quality
calcaneal tendon	UBERON:0003701	62.74	gold quality
corpus callosum	UBERON:0002336	62.35	gold quality
islet of Langerhans	UBERON:0000006	62.06	gold quality
pituitary gland	UBERON:0000007	61.54	gold quality
prefrontal cortex	UBERON:0000451	60.84	gold quality
colonic epithelium	UBERON:0000397	60.00	gold quality
mucosa of stomach	UBERON:0001199	59.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting FSIP1, 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-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-499A-3P	99.18	69.20	1392

Literature-anchored findings (GeneRIF, showing 11)

• association between the variants in FSIP1 and aspirin intolerant asthma occurrence among asthmatics in a Korean population (PMID:20513247)
• prevalence and uniformity of FSIP1 expression in breast tumors (PMID:23905897)
• FSIP1 may play an important role in the tumorigenesis and invasion of breast cancer and is a potential biomarker for breast cancer diagnosis or prognosis. (PMID:25826084)
• Results suggest that evaluating fibrous sheath interacting protein 1 (FSIP1) status in addition to TNM stage during routine pathological examinations could improve prognostic predictions in non-small cell lung cancer (NSCLC) patients. (PMID:28086239)
• FSIP1 binds HER2 directly, which regulates breast cancer growth and invasiveness (PMID:28674022)
• High FSIP1 expression is associated with drug resistance in triple-negative breast cancer. (PMID:30509973)
• FSIP1 bound to the multidrug resistance protein 1 (MRP1) and stabilized it, and knocking out FSIP1 decreased MRP1 expression and increased cellular docetaxel accumulation. In sum, FSIP1 promotes breast carcinogenesis and mediates docetaxel resistance. (PMID:30814489)
• FSIP1 overexpression correlated with decreased overall survival in hormone receptor-positive breast cancer patients. (PMID:31713931)
• Loss-of-function variants in FSIP1 identified by targeted sequencing are associated with one particular subtype of mucosal melanoma. (PMID:32717308)
• FSIP1 Is Associated with Poor Prognosis and Can Be Used to Construct a Prognostic Model in Gastric Cancer. (PMID:35692888)
• FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway. (PMID:37460715)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fsip1	ENSMUSG00000027344
rattus_norvegicus	Fsip1	ENSRNOG00000005888

Protein

Protein identifiers

Fibrous sheath-interacting protein 1 — Q8NA03 (reviewed: Q8NA03)

All UniProt accessions (4): Q8NA03, A0A2R8Y503, A0A2R8YHB5, H0YNV9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FSIP1 family.

RefSeq proteins (2): NP_001311267, NP_689810* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026246	Fsip1	Family

Pfam: PF15554

UniProt features (18 total): sequence variant 6, compositionally biased region 4, region of interest 3, sequence conflict 2, chain 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA03-F1	61.23	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 87

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): WHITEHURST_PACLITAXEL_SENSITIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, chr15q14, TGTYNNNNNRGCARM_UNKNOWN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, ATF6_TARGET_GENES, BANP_TARGET_GENES, CIITA_TARGET_GENES, DYRK1A_TARGET_GENES, ELF2_TARGET_GENES, HES2_TARGET_GENES, HOXC6_TARGET_GENES, IRF5_TARGET_GENES, PITX1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FSIP1	HSD17B10	Q99714	982
FSIP1	DHRS11	Q6UWP2	881
FSIP1	TRMT10C	Q7L0Y3	836
FSIP1	PRORP	O15091	805
FSIP1	AKAP4	Q5JQC9	755
FSIP1	HADH	Q16836	630
FSIP1	HUWE1	Q7Z6Z7	594
FSIP1	ELAC2	Q9BQ52	479
FSIP1	ESR1	P03372	466
FSIP1	APP	P05067	460
FSIP1	STARD6	P59095	432
FSIP1	FMR1NB	Q8N0W7	431
FSIP1	TRMT10B	Q6PF06	419
FSIP1	FSIP2	Q5CZC0	416
FSIP1	C11orf86	A6NJI1	397

IntAct

4 interactions, top by confidence:

A	B	Type	Score
POLR2A	FSIP1	psi-mi:“MI:0915”(physical association)	0.400
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FSIP1	PHB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): FSIP1 (Affinity Capture-MS), FSIP1 (Two-hybrid), FSIP1 (Affinity Capture-MS), FSIP1 (Proximity Label-MS), FSIP1 (Affinity Capture-MS), FSIP1 (Negative Genetic), FSIP1 (Positive Genetic), FSIP1 (Proximity Label-MS), FSIP1 (Cross-Linking-MS (XL-MS)), TMTC3 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A1L2Y1, A2ALV5, A9JRX0, B2GUZ2, D3ZSP7, F1QB81, O35892, O70608, O75113, P23497, P70347, Q0P5X5, Q13129, Q16533, Q2T9I9, Q3U1D0, Q5CZC0, Q5H9M0, Q5REF4, Q5RHB5, Q5SW75, Q5T4T6, Q5T5J6, Q5XG69, Q5ZLE9, Q60664, Q63HN8, Q7M6U3, Q7Z4H7, Q80VH0, Q8BVK9, Q8C263, Q8CCC3, Q8NA03, Q90WN7, Q92844, Q96QP1

Diamond homologs: A1L2Y1, Q566N9, Q66H16, Q8NA03, Q95LY3, Q9D3V5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	76
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564194	GRCh37/hg19 15q14-15.1(chr15:38170429-40775075)x1	Pathogenic

SpliceAI

3841 predictions. Top by Δscore:

Variant	Effect	Δscore
15:39588524:A:AG	acceptor_gain	1.0000
15:39588525:G:GA	acceptor_gain	1.0000
15:39588525:GTC:G	acceptor_gain	1.0000
15:39588525:GTCA:G	acceptor_gain	1.0000
15:39588951:T:A	acceptor_gain	1.0000
15:39588955:TCAG:T	acceptor_loss	1.0000
15:39588957:A:AG	acceptor_gain	1.0000
15:39588957:AGAT:A	acceptor_gain	1.0000
15:39588958:G:GG	acceptor_gain	1.0000
15:39588958:GATG:G	acceptor_gain	1.0000
15:39589083:TGAGG:T	donor_loss	1.0000
15:39589086:GGT:G	donor_loss	1.0000
15:39589087:GTGAG:G	donor_loss	1.0000
15:39589088:T:G	donor_loss	1.0000
15:39589197:CATA:C	acceptor_loss	1.0000
15:39589198:A:AG	acceptor_gain	1.0000
15:39589198:ATAGT:A	acceptor_gain	1.0000
15:39589199:T:G	acceptor_gain	1.0000
15:39589200:A:AC	acceptor_loss	1.0000
15:39589200:A:AG	acceptor_gain	1.0000
15:39589200:AGT:A	acceptor_gain	1.0000
15:39589201:G:A	acceptor_loss	1.0000
15:39589201:G:GA	acceptor_gain	1.0000
15:39589201:GT:G	acceptor_gain	1.0000
15:39589201:GTG:G	acceptor_gain	1.0000
15:39589201:GTGC:G	acceptor_gain	1.0000
15:39589201:GTGCA:G	acceptor_gain	1.0000
15:39589353:AGGT:A	donor_loss	1.0000
15:39589355:G:GA	donor_loss	1.0000
15:39589802:CAGG:C	acceptor_loss	1.0000

AlphaMissense

3877 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:39739683:A:C	F254L	0.979
15:39739683:A:T	F254L	0.979
15:39739685:A:G	F254L	0.979
15:39741860:A:C	F200L	0.977
15:39741860:A:T	F200L	0.977
15:39741862:A:G	F200L	0.977
15:39738137:A:G	L282P	0.973
15:39713505:C:G	R376P	0.968
15:39763855:A:C	F175L	0.968
15:39763855:A:T	F175L	0.968
15:39763857:A:G	F175L	0.968
15:39738146:A:G	L279P	0.961
15:39765705:C:G	A118P	0.960
15:39713490:C:G	R381P	0.959
15:39713466:A:G	L389P	0.950
15:39739671:G:C	N258K	0.945
15:39739671:G:T	N258K	0.945
15:39765683:A:G	L125P	0.941
15:39713487:A:G	L382P	0.939
15:39765692:A:G	M122T	0.938
15:39739684:A:G	F254S	0.932
15:39741861:A:G	F200S	0.931
15:39765608:A:G	L150P	0.930
15:39763856:A:G	F175S	0.925
15:39738197:G:T	A262D	0.924
15:39776509:C:G	G6R	0.924
15:39776509:C:T	G6R	0.924
15:39617823:G:C	F537L	0.922
15:39617823:G:T	F537L	0.922
15:39617825:A:G	F537L	0.922

dbSNP variants (sampled 300 via entrez): RS1000003426 (15:39597935 G>A), RS1000012797 (15:39688493 T>C), RS1000017427 (15:39639430 CA>C), RS1000020386 (15:39669000 A>C), RS1000046771 (15:39619862 A>G), RS1000066470 (15:39688780 C>T), RS1000068327 (15:39638206 G>C), RS1000077855 (15:39620299 G>A), RS1000082862 (15:39645971 G>A), RS1000086781 (15:39771874 T>C), RS1000122180 (15:39746827 G>A), RS1000150713 (15:39705992 G>A), RS1000165511 (15:39655231 T>C), RS1000182417 (15:39662148 G>A), RS1000206180 (15:39663643 T>C)

Disease associations

OMIM: gene MIM:615795 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001762_820	Obesity-related traits	2.000000e-06
GCST006019_38	Gamma glutamyl transferase levels	5.000000e-08
GCST006479_33	Diverticular disease	3.000000e-06
GCST007005_7	Logical memory (immediate recall) in normal cognition	5.000000e-07
GCST008972_254	Urate levels	2.000000e-17
GCST008972_55	Urate levels	9.000000e-07
GCST011349_22	Gamma glutamyl transferase levels	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0009959	diverticular disease
EFO:0004874	memory performance
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7179742	Toxicity	3	aspirin	Asthma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7179742	FSIP1	3	2.50	1	aspirin

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	3
bisphenol A	affects expression, affects cotreatment, increases methylation	2
sodium arsenite	increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
methylmercuric chloride	decreases expression	1
hydroquinone	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases methylation	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Vorinostat	increases expression	1
Arsenic	increases response to substance	1
Aspirin	affects response to substance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Copper	affects binding, increases expression	1
Cytarabine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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