FLYWCH2

Summary

FLYWCH2 (FLYWCH family member 2, HGNC:25178) is a protein-coding gene on chromosome 16p13.3, encoding FLYWCH family member 2 (Q96CP2).

Enables RNA binding activity.

Source: NCBI Gene 114984 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_138439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25178
Approved symbol	FLYWCH2
Name	FLYWCH family member 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162076
Ensembl biotype	protein_coding
Entrez	114984

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000293981, ENST00000396958, ENST00000572006, ENST00000572786, ENST00000573965, ENST00000872321, ENST00000872322, ENST00000872323, ENST00000872324, ENST00000872325, ENST00000922187, ENST00000943117, ENST00000943118, ENST00000943119, ENST00000943120, ENST00000943121

RefSeq mRNA: 3 — MANE Select: NM_138439 NM_001142499, NM_001142500, NM_138439

CCDS: CCDS10482

Canonical transcript exons

ENST00000396958 — 4 exons

Exon	Start	End
ENSE00001062481	2896352	2896771
ENSE00001062482	2895220	2895320
ENSE00001526883	2883215	2883366
ENSE00003850085	2899049	2899365

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.0451 / max 250.6128, expressed in 1818 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152333	27.1760	1814
152332	5.6217	1728
152329	2.0480	1188
152330	1.2578	927
152334	1.1316	746
152331	0.8100	549

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	93.52	gold quality
cerebellar vermis	UBERON:0004720	93.12	gold quality
left adrenal gland cortex	UBERON:0035825	92.79	gold quality
hypothalamus	UBERON:0001898	92.68	gold quality
right adrenal gland cortex	UBERON:0035827	92.61	gold quality
left adrenal gland	UBERON:0001234	92.42	gold quality
right adrenal gland	UBERON:0001233	92.39	gold quality
adrenal cortex	UBERON:0001235	92.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.05	gold quality
cerebellar cortex	UBERON:0002129	91.95	gold quality
cerebellar hemisphere	UBERON:0002245	91.94	gold quality
adenohypophysis	UBERON:0002196	91.63	gold quality
putamen	UBERON:0001874	91.55	gold quality
apex of heart	UBERON:0002098	91.50	gold quality
cerebellum	UBERON:0002037	91.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.87	gold quality
adrenal gland	UBERON:0002369	90.46	gold quality
prefrontal cortex	UBERON:0000451	90.44	gold quality
pituitary gland	UBERON:0000007	90.37	gold quality
right atrium auricular region	UBERON:0006631	90.31	gold quality
caudate nucleus	UBERON:0001873	90.22	gold quality
amygdala	UBERON:0001876	90.21	gold quality
nucleus accumbens	UBERON:0001882	90.20	gold quality
cardiac atrium	UBERON:0002081	90.05	gold quality
spleen	UBERON:0002106	90.04	gold quality
anterior cingulate cortex	UBERON:0009835	90.02	gold quality
right lobe of thyroid gland	UBERON:0001119	89.93	gold quality
left lobe of thyroid gland	UBERON:0001120	89.90	gold quality
spinal cord	UBERON:0002240	89.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting FLYWCH2, 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-548E-5P	99.89	72.73	4486
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6890-5P	92.89	65.83	442

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Flywch2	ENSMUSG00000023911
rattus_norvegicus	Flywch2	ENSRNOG00000004461

Paralogs (1): FLYWCH1 (ENSG00000059122)

Protein

Protein identifiers

FLYWCH family member 2 — Q96CP2 (reviewed: Q96CP2)

All UniProt accessions (3): Q96CP2, I3L1Y9, I3L4I0

RefSeq proteins (3): NP_001135971, NP_001135972, NP_612448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029279	FLYWCH_N	Domain
IPR040312	FWCH1/FWCH2	Family

Pfam: PF15423

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CP2-F1	67.03	0.05

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): 21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, TGCGCANK_UNKNOWN, MODULE_205, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, VDR_Q6, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, KOHOUTEK_CCNT2_TARGETS, SNF5_DN.V1_DN, CEBPZ_TARGET_GENES, CREB3L4_TARGET_GENES, FOXN3_TARGET_GENES, HHEX_TARGET_GENES, RBM34_TARGET_GENES, ZNF22_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1

Protein interactions and networks

STRING

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLYWCH2	HCFC1R1	Q9NWW0	491
FLYWCH2	BICDL2	A1A5D9	487
FLYWCH2	KRABD5	Q7Z2F6	473
FLYWCH2	THEM6	Q8WUY1	471
FLYWCH2	TMEM235	A6NFC5	447
FLYWCH2	FAM86C1P	Q9NVL1	445
FLYWCH2	TMEM200A	Q86VY9	402
FLYWCH2	MOSMO	Q8NHV5	394
FLYWCH2	THOC6	Q86W42	392
FLYWCH2	NHSL3	Q9P206	391
FLYWCH2	SYNGR2	O43760	387
FLYWCH2	PRSS33	Q8NF86	383
FLYWCH2	PCP4L1	A6NKN8	372
FLYWCH2	ERI2	A8K979	367
FLYWCH2	PLEKHG1	Q9ULL1	367

IntAct

68 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
CD9	IGSF8	psi-mi:“MI:0914”(association)	0.760
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
SLX1A	BACH1	psi-mi:“MI:0914”(association)	0.530
FLYWCH2	BAG4	psi-mi:“MI:0914”(association)	0.530
BPGM	FLYWCH2	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
RAB6B	SBF1	psi-mi:“MI:0914”(association)	0.530
CDR2	IGSF3	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PPARG	FLYWCH2	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
PSME3	ZNF891	psi-mi:“MI:0914”(association)	0.350
PSMC3		psi-mi:“MI:0914”(association)	0.350
SPATA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350
PCDHB11	CBX4	psi-mi:“MI:0914”(association)	0.350
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
TBC1D22A	ACSL4	psi-mi:“MI:0914”(association)	0.350
HDAC7	ZMYM6	psi-mi:“MI:0914”(association)	0.350
GRN	GNB2	psi-mi:“MI:0914”(association)	0.350
WDR54	OSCP1	psi-mi:“MI:0914”(association)	0.350
HSPA8	AGPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (123): FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), RXRB (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), TRUB1 (Co-fractionation), FLYWCH2 (Proximity Label-MS), FLYWCH2 (Proximity Label-MS), GET4 (Two-hybrid)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NP61, A7E321, E9PGG2, P07516, P18302, Q15554, Q2TBI2, Q32LQ1, Q3TVI4, Q3TYX8, Q49AM3, Q4KLY2, Q5FVJ4, Q5R866, Q5R9P4, Q5RA50, Q5SU73, Q5SXM2, Q5T6C5, Q5T7N3, Q5VTJ3, Q60829, Q6J4I0, Q6PG95, Q6PJ61, Q6ZMQ8, Q6ZNE9, Q7TSG2, Q7TSX9, Q80SU3, Q80VJ8, Q86V42, Q8BG26, Q8BG80, Q8BRJ3, Q8C0R7, Q8IY92, Q8K124

Diamond homologs: Q4VC44, Q5R9P4, Q8CI03, Q96CP2, Q9CQE9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
CLEC7A (Dectin-1) signaling	5	11.7×	1e-02
Regulation of HSF1-mediated heat shock response	5	11.4×	1e-02
Cellular responses to stress	9	5.4×	8e-03
Cellular responses to stimuli	10	5.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

715 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2896348:TTAG:T	acceptor_loss	0.9900
16:2896349:TA:T	acceptor_loss	0.9900
16:2896350:A:AT	acceptor_loss	0.9900
16:2896385:G:GT	donor_gain	0.9900
16:2883347:G:GT	donor_gain	0.9800
16:2883348:G:T	donor_gain	0.9800
16:2883372:G:GT	donor_gain	0.9800
16:2894342:G:GT	donor_gain	0.9800
16:2894470:GGCGC:G	donor_gain	0.9800
16:2895217:CA:C	acceptor_loss	0.9800
16:2895218:A:AC	acceptor_loss	0.9800
16:2895219:G:GT	acceptor_loss	0.9800
16:2895317:CAAGG:C	donor_loss	0.9800
16:2895318:AAG:A	donor_loss	0.9800
16:2895320:GGTT:G	donor_loss	0.9800
16:2895321:G:GA	donor_loss	0.9800
16:2895322:T:C	donor_loss	0.9800
16:2896350:A:AG	acceptor_gain	0.9800
16:2896350:AGGAC:A	acceptor_gain	0.9800
16:2896351:G:GG	acceptor_gain	0.9800
16:2896351:GGACG:G	acceptor_gain	0.9800
16:2895218:A:AG	acceptor_gain	0.9700
16:2895219:G:GG	acceptor_gain	0.9700
16:2895219:GGCCA:G	acceptor_gain	0.9700
16:2896351:GGAC:G	acceptor_gain	0.9700
16:2883363:GTCG:G	donor_gain	0.9600
16:2883362:CGTCG:C	donor_loss	0.9500
16:2883365:CGGTG:C	donor_loss	0.9500
16:2883366:GGTGA:G	donor_loss	0.9500
16:2883367:GTGA:G	donor_loss	0.9500

AlphaMissense

896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2896564:T:C	F39L	0.978
16:2896566:C:A	F39L	0.978
16:2896566:C:G	F39L	0.978
16:2896577:T:A	V43D	0.970
16:2896580:T:C	L44P	0.970
16:2896583:T:C	L45P	0.970
16:2896580:T:A	L44Q	0.964
16:2896574:T:A	L42Q	0.962
16:2896583:T:A	L45H	0.962
16:2896643:T:A	V65D	0.961
16:2896574:T:C	L42P	0.955
16:2896641:T:G	C64W	0.955
16:2896640:G:A	C64Y	0.950
16:2896639:T:C	C64R	0.944
16:2896580:T:G	L44R	0.939
16:2896571:A:T	K41I	0.927
16:2896574:T:G	L42R	0.918
16:2896583:T:G	L45R	0.915
16:2896648:T:C	S67P	0.914
16:2896630:G:C	G61R	0.909
16:2896647:G:A	M66I	0.909
16:2896647:G:C	M66I	0.909
16:2896647:G:T	M66I	0.909
16:2896688:T:A	L80H	0.909
16:2896586:C:T	T46I	0.906
16:2896654:G:T	G69W	0.898
16:2896589:C:A	A47D	0.895
16:2896646:T:G	M66R	0.891
16:2896600:A:C	S51R	0.890
16:2896602:C:A	S51R	0.890

dbSNP variants (sampled 300 via entrez): RS1000044314 (16:2891551 C>A,G,T), RS1000048971 (16:2888365 A>C,G,T), RS1000115750 (16:2890788 A>C,T), RS1000124235 (16:2897277 G>A), RS1000344981 (16:2882769 G>A,C), RS1000420188 (16:2891657 G>C), RS1000573245 (16:2899725 C>A,G), RS1000714423 (16:2886001 T>A), RS1001383559 (16:2887306 C>T), RS1001406911 (16:2883043 G>A,C,T), RS1001459934 (16:2887564 T>A), RS1001716238 (16:2894940 G>A), RS1001752599 (16:2887462 T>C), RS1002146911 (16:2899357 A>G), RS1002526836 (16:2893032 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	3
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tetrahydropalmatine	decreases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Manganese	increases abundance, increases expression	1
Potassium Dichromate	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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