RESF1

Summary

RESF1 (retroelement silencing factor 1, HGNC:25559) is a protein-coding gene on chromosome 12p11.21, encoding Retroelement silencing factor 1 (Q9HCM1). Plays a role in the regulation of imprinted gene expression, regulates repressive epigenetic modifications associated with SETDB1.

Predicted to enable histone binding activity and histone methyltransferase binding activity. Predicted to be involved in transposable element silencing by heterochromatin formation. Predicted to act upstream of or within response to bacterium. Predicted to be active in nucleus.

Source: NCBI Gene 55196 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 355 total
• MANE Select transcript: NM_018169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25559
Approved symbol	RESF1
Name	retroelement silencing factor 1
Location	12p11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20696, FLJ10652, UTA2-1, GET
Ensembl gene	ENSG00000174718
Ensembl biotype	protein_coding
OMIM	615621
Entrez	55196

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000312561, ENST00000381054, ENST00000397578, ENST00000535596, ENST00000535606, ENST00000540924, ENST00000541981, ENST00000543763, ENST00000870365, ENST00000913392, ENST00000913393, ENST00000913394, ENST00000913395, ENST00000913396, ENST00000913397, ENST00000913398, ENST00000952432, ENST00000952433, ENST00000952434, ENST00000952435

RefSeq mRNA: 1 — MANE Select: NM_018169 NM_018169

CCDS: CCDS8725

Canonical transcript exons

ENST00000312561 — 6 exons

Exon	Start	End
ENSE00001186075	31992378	31993107
ENSE00001269832	31980878	31985957
ENSE00001487366	31970189	31970356
ENSE00001487367	31960777	31960871
ENSE00001487370	31959415	31959491
ENSE00003624701	31987239	31987322

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5430 / max 2585.0853, expressed in 1764 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124955	17.9850	1503
124954	13.2226	1618
124951	1.7868	265
124957	0.9033	333
124953	0.6740	374
124952	0.5684	106
124964	0.4404	171
124956	0.3809	172
124961	0.3243	142
124958	0.2411	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.72	gold quality
lymph node	UBERON:0000029	97.70	gold quality
jejunal mucosa	UBERON:0000399	97.68	gold quality
blood	UBERON:0000178	97.58	gold quality
granulocyte	CL:0000094	97.49	gold quality
spleen	UBERON:0002106	97.09	gold quality
buccal mucosa cell	CL:0002336	97.03	gold quality
left ovary	UBERON:0002119	96.40	gold quality
leukocyte	CL:0000738	96.34	gold quality
right ovary	UBERON:0002118	96.28	gold quality
monocyte	CL:0000576	96.24	gold quality
mononuclear cell	CL:0000842	96.18	gold quality
epithelium of nasopharynx	UBERON:0001951	96.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.05	gold quality
nasopharynx	UBERON:0001728	96.04	gold quality
ovary	UBERON:0000992	95.95	gold quality
secondary oocyte	CL:0000655	95.81	gold quality
germinal epithelium of ovary	UBERON:0001304	95.73	gold quality
vermiform appendix	UBERON:0001154	95.64	gold quality
trabecular bone tissue	UBERON:0002483	95.59	gold quality
endometrium	UBERON:0001295	95.36	gold quality
right lobe of liver	UBERON:0001114	94.94	gold quality
oocyte	CL:0000023	94.87	gold quality
duodenum	UBERON:0002114	94.29	gold quality
bone marrow cell	CL:0002092	94.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.06	gold quality
calcaneal tendon	UBERON:0003701	94.06	gold quality
superficial temporal artery	UBERON:0001614	93.96	gold quality
bone marrow	UBERON:0002371	93.66	gold quality
tonsil	UBERON:0002372	93.53	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	952.97
E-CURD-122	yes	48.99
E-MTAB-9543	yes	15.79
E-GEOD-106540	no	1603.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting RESF1, 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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Resf1	ENSMUSG00000032712
rattus_norvegicus	Resf1	ENSRNOG00000036913

Protein

Protein identifiers

Retroelement silencing factor 1 — Q9HCM1 (reviewed: Q9HCM1)

All UniProt accessions (3): Q9HCM1, F5H488, J3KPI3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of imprinted gene expression, regulates repressive epigenetic modifications associated with SETDB1. Required for the recruitment or accumulation of SETDB1 to the endogenous retroviruses (ERVs) and maintenance of repressive chromatin configuration, contributing to a subset of the SETDB1-dependent ERV silencing in embryonic stem cells.

Subunit / interactions. Interacts with SETDB1.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_060639* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027866	RESF1	Family

Pfam: PF15395

UniProt features (45 total): sequence variant 16, compositionally biased region 8, region of interest 6, modified residue 6, cross-link 6, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCM1-F1	38.45	0.02

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 (12): 221, 1145, 1240, 1358, 1708, 1740, 216, 707, 1136, 1528, 1636, 1723

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, CAGCTG_AP4_Q5, chr12p11, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, YGACNNYACAR_UNKNOWN, FREAC3_01, KORKOLA_EMBRYONAL_CARCINOMA_UP, TGIF_01, KIM_GERMINAL_CENTER_T_HELPER_UP, BENPORATH_NOS_TARGETS, BASAKI_YBX1_TARGETS_DN

GO Biological Process (1): transposable element silencing by heterochromatin formation (GO:0141005)

GO Molecular Function (3): histone binding (GO:0042393), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transposable element silencing	1
constitutive heterochromatin formation	1
protein binding	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RESF1	GARRE1	O15063	543
RESF1	ARHGEF10L	Q9HCE6	519
RESF1	SPRYD3	Q8NCJ5	448
RESF1	AFMID	Q63HM1	448
RESF1	USO1	O60763	435
RESF1	PEMT	Q9UBM1	425
RESF1	CZIB	Q9NWV4	423
RESF1	PHC1	P78364	423
RESF1	MYO1B	O43795	418
RESF1	RPS24	P16632	410
RESF1	KHK	P50053	409
RESF1	TRIM28	Q13263	408
RESF1	RSAD1	Q9HA92	407
RESF1	LRATD1	Q96KN4	402
RESF1	SETDB1	Q15047	389

IntAct

43 interactions, top by confidence:

A	B	Type	Score
KRT86	RESF1	psi-mi:“MI:0915”(physical association)	0.560
KRT36	RESF1	psi-mi:“MI:0915”(physical association)	0.560
GABARAP	RESF1	psi-mi:“MI:0407”(direct interaction)	0.440
GABARAPL1	RESF1	psi-mi:“MI:0407”(direct interaction)	0.440
GABARAPL2	RESF1	psi-mi:“MI:0407”(direct interaction)	0.440
RESF1	VIM	psi-mi:“MI:0915”(physical association)	0.400
RESF1	TOP2A	psi-mi:“MI:0915”(physical association)	0.400
TBC1D4	RESF1	psi-mi:“MI:0915”(physical association)	0.370
vBCL2	RESF1	psi-mi:“MI:0915”(physical association)	0.370
RESF1	GAMMAHV.ORF35	psi-mi:“MI:0915”(physical association)	0.370
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
USP20	MYO9A	psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
SRF	ZNF292	psi-mi:“MI:2364”(proximity)	0.270
ERG	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
ZMYM2	ZBTB5	psi-mi:“MI:2364”(proximity)	0.270
RESF1	EXOC1	psi-mi:“MI:0915”(physical association)	0.000
EXOC1	RESF1	psi-mi:“MI:0915”(physical association)	0.000
RESF1	KRT86	psi-mi:“MI:0915”(physical association)	0.000
RESF1	KRT36	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): KIAA1551 (Affinity Capture-MS), KIAA1551 (Biochemical Activity), KIAA1551 (Affinity Capture-MS), KIAA1551 (Two-hybrid), KIAA1551 (Two-hybrid), KIAA1551 (Proximity Label-MS), KIAA1551 (Proximity Label-MS), KIAA1551 (Affinity Capture-MS), KIAA1551 (Affinity Capture-MS), KIAA1551 (Affinity Capture-MS), KIAA1551 (Affinity Capture-MS), KIAA1551 (Affinity Capture-MS), KIAA1551 (Proximity Label-MS), KIAA1551 (Proximity Label-MS), KIAA1551 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1S3C4H6, A0A338P6K9, A2RRX6, A6NCI8, B9FXV5, C7IW64, E9QAT4, O13658, O14029, O14269, O60187, O74808, P0C9Z7, P15822, P48415, P80074, P86273, Q10076, Q14207, Q196W1, Q2KHR3, Q3V0A6, Q3Y4E1, Q4JK59, Q5DTW7, Q5R782, Q5Z8V7, Q61624, Q62806, Q66IN2, Q6AYN3, Q6CM10, Q6N021, Q6YXY2, Q76E23, Q76KD6, Q8BMA5, Q8K4L6, Q8NEV8

Diamond homologs: Q5DTW7, Q9HCM1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	27.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	305
Likely benign	32
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1001 predictions. Top by Δscore:

Variant	Effect	Δscore
12:31959488:GTCG:G	donor_gain	0.9900
12:31959492:G:C	donor_loss	0.9900
12:31959492:G:GG	donor_gain	0.9900
12:31970188:GCT:G	acceptor_gain	0.9900
12:31970233:A:AG	acceptor_gain	0.9900
12:31970332:G:GG	donor_gain	0.9900
12:31992376:A:AG	acceptor_gain	0.9900
12:31992377:G:GG	acceptor_gain	0.9900
12:31992377:GATA:G	acceptor_gain	0.9900
12:31970331:A:AG	donor_gain	0.9800
12:31980872:TTACA:T	acceptor_loss	0.9800
12:31980873:TACAG:T	acceptor_loss	0.9800
12:31980874:ACAG:A	acceptor_loss	0.9800
12:31980875:CA:C	acceptor_loss	0.9800
12:31980876:A:AT	acceptor_loss	0.9800
12:31987508:GC:G	donor_gain	0.9800
12:31959489:TCG:T	donor_gain	0.9700
12:31959490:CG:C	donor_gain	0.9700
12:31959491:GG:G	donor_gain	0.9700
12:31980876:A:AG	acceptor_gain	0.9700
12:31980877:G:GG	acceptor_gain	0.9700
12:31992373:CTTA:C	acceptor_loss	0.9700
12:31992374:TTA:T	acceptor_loss	0.9700
12:31992375:TAGAT:T	acceptor_loss	0.9700
12:31992376:A:G	acceptor_loss	0.9700
12:31992377:GAT:G	acceptor_gain	0.9700
12:31992377:GATAA:G	acceptor_gain	0.9700
12:31960771:CCCTA:C	acceptor_loss	0.9600
12:31960772:CCTAG:C	acceptor_loss	0.9600
12:31960773:CTA:C	acceptor_loss	0.9600

AlphaMissense

11590 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:31985715:T:C	F1587S	0.997
12:31985859:T:C	F1635S	0.996
12:31985714:T:C	F1587L	0.995
12:31985716:T:A	F1587L	0.995
12:31985716:T:G	F1587L	0.995
12:31983237:C:A	A761D	0.994
12:31985858:T:C	F1635L	0.994
12:31985860:T:A	F1635L	0.994
12:31985860:T:G	F1635L	0.994
12:31984128:T:C	L1058P	0.992
12:31984139:T:C	F1062L	0.992
12:31984141:T:A	F1062L	0.992
12:31984141:T:G	F1062L	0.992
12:31982993:T:A	W680R	0.991
12:31982993:T:C	W680R	0.991
12:31987268:T:A	W1678R	0.990
12:31987268:T:C	W1678R	0.990
12:31984140:T:C	F1062S	0.987
12:31985715:T:G	F1587C	0.987
12:31983236:G:C	A761P	0.986
12:31985709:T:A	V1585D	0.984
12:31984517:T:C	C1188R	0.983
12:31985739:T:A	I1595N	0.983
12:31982184:T:C	L410P	0.982
12:31982995:G:C	W680C	0.982
12:31982995:G:T	W680C	0.982
12:31984484:T:A	W1177R	0.982
12:31984484:T:C	W1177R	0.982
12:31985739:T:G	I1595S	0.982
12:31985745:T:A	L1597H	0.981

dbSNP variants (sampled 300 via entrez): RS1000130362 (12:31979275 C>A,G), RS1000292032 (12:31983883 G>A), RS1000314442 (12:31978416 C>T), RS1000350362 (12:31978125 T>A,C), RS1000503934 (12:31979126 T>C), RS1000515200 (12:31962860 G>A,T), RS1000543135 (12:31963943 G>A), RS1000546761 (12:31958183 G>A,C), RS1000566919 (12:31959174 C>T), RS1000598299 (12:31958833 C>G), RS1000703460 (12:31989306 G>C), RS1000770693 (12:31990077 G>A), RS1000771034 (12:31990565 G>A), RS1000858773 (12:31974726 T>C), RS1000988205 (12:31969085 C>A,T)

Disease associations

OMIM: gene MIM:615621 | 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_401	Obesity-related traits	5.000000e-06
GCST004635_24	Testicular germ cell tumor	2.000000e-11
GCST008466_6	Alanine aminotransferase levels in non-alcoholic fatty liver disease	6.000000e-06
GCST90002381_488	Eosinophil count	2.000000e-15
GCST90002382_308	Eosinophil percentage of white cells	9.000000e-17
GCST90002396_524	Mean reticulocyte volume	2.000000e-15
GCST90002397_424	Mean spheric corpuscular volume	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
jinfukang	decreases expression	1
NSC 689534	increases expression, affects binding	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	decreases expression	1
Nickel	increases expression	1
Plant Oils	increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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