RFC3

Summary

RFC3 (replication factor C subunit 3, HGNC:9971) is a protein-coding gene on chromosome 13q13.2, encoding Replication factor C subunit 3 (P40938). Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kDa. This gene encodes the 38 kDa subunit. This subunit is essential for the interaction between the 140 kDa subunit and the core complex that consists of the 36, 37, and 40 kDa subunits. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 5983 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_002915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9971
Approved symbol	RFC3
Name	replication factor C subunit 3
Location	13q13.2
Locus type	gene with protein product
Status	Approved
Aliases	RFC38, MGC5276
Ensembl gene	ENSG00000133119
Ensembl biotype	protein_coding
OMIM	600405
Entrez	5983

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000380071, ENST00000434425, ENST00000616236, ENST00000931924

RefSeq mRNA: 2 — MANE Select: NM_002915 NM_002915, NM_181558

CCDS: CCDS45025, CCDS9352

Canonical transcript exons

ENST00000380071 — 9 exons

Exon	Start	End
ENSE00000680275	33835148	33835217
ENSE00000817036	33821132	33821269
ENSE00000817037	33823917	33823984
ENSE00000817038	33825789	33825886
ENSE00000817040	33830719	33830855
ENSE00000817041	33831256	33831354
ENSE00001349478	33829836	33830017
ENSE00001483649	33836104	33837500
ENSE00001912539	33818149	33818265

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 90.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9831 / max 312.3113, expressed in 1731 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134735	15.4000	1661
134734	2.8611	1038
134733	1.5447	803
134736	1.0709	550
134732	0.1063	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.97	gold quality
ventricular zone	UBERON:0003053	89.69	gold quality
embryo	UBERON:0000922	89.47	gold quality
ganglionic eminence	UBERON:0004023	88.54	gold quality
secondary oocyte	CL:0000655	87.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.31	gold quality
right adrenal gland cortex	UBERON:0035827	85.39	gold quality
endometrium epithelium	UBERON:0004811	84.57	gold quality
right adrenal gland	UBERON:0001233	84.55	gold quality
left adrenal gland	UBERON:0001234	84.13	gold quality
left adrenal gland cortex	UBERON:0035825	84.11	gold quality
vermiform appendix	UBERON:0001154	83.91	gold quality
rectum	UBERON:0001052	83.57	gold quality
bone marrow	UBERON:0002371	83.48	gold quality
amniotic fluid	UBERON:0000173	83.32	gold quality
adrenal cortex	UBERON:0001235	83.26	gold quality
adrenal gland	UBERON:0002369	83.18	gold quality
tongue squamous epithelium	UBERON:0006919	83.04	gold quality
trabecular bone tissue	UBERON:0002483	82.96	gold quality
calcaneal tendon	UBERON:0003701	81.84	gold quality
endometrium	UBERON:0001295	81.80	gold quality
adrenal tissue	UBERON:0018303	81.55	gold quality
lymph node	UBERON:0000029	81.07	gold quality
tendon	UBERON:0000043	80.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.20	gold quality
placenta	UBERON:0001987	79.91	gold quality
caecum	UBERON:0001153	79.82	gold quality
tonsil	UBERON:0002372	79.71	gold quality
lower lobe of lung	UBERON:0008949	79.25	gold quality
esophagus squamous epithelium	UBERON:0006920	79.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.44
E-GEOD-99795	no	233.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CREB1, E2F4, TFDP2

miRNA regulators (miRDB)

82 targeting RFC3, 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-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
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-4262	100.00	73.26	3931
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-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3912-5P	99.95	66.11	925
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• RFC3 mutation and loss of RFC3 expression occur in large fractions of gastric and colorectal cancers and suggest that these alterations may contribute to the cancer pathogenesis by deregulating DNA repair and replication. (PMID:20573375)
• Data identified RFC3 as a candidate oncogene amplified in esophageal adenocarcinoma (EAC). (PMID:22328562)
• 9-cis-RA-activated RXRalpha suppresses the growth of retinoid-sensitive breast cancer and embryonic cells through RFC3. (PMID:22949521)
• our findings suggest that RFC3 protein is an important and independent biomarker with prognostic implications for patients with ovarian carcinoma. (PMID:25030735)
• High RFC3 expression is associated with neoplastic myelopoiesis. (PMID:25541153)
• The expression level of RFC3 was markedly upregulated in the HCC tissues and cells. (PMID:26397132)
• The expression level of RFC3 was remarkably up-regulated in ovarian cancer OVCAR-3 cells. Down-regulation of RFC3 expression arrested the cell cycle of OVCAR-3 cell in the S-phase and induced apoptosis. (PMID:26464638)
• Ectopic expression of RFC3 induced epithelialmesenchymal transition (EMT), as determined by downregulation of Ecadherin, and upregulation of Ncadherin, vimentin and Wnt signaling target genes, including cMYC, Wnt1 and betacatenin, and the ratio of phosphorylatedglycogen synthase kinase 3 (GSK3)beta (Ser9)/GSK3beta. (PMID:31661124)
• IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3. (PMID:34930359)
• RFC3 serves as a novel prognostic biomarker and target for head and neck squamous cell carcinoma. (PMID:37861747)
• Abnormal activation of RFC3, A YAP1/TEAD downstream target, promotes gastric cancer progression. (PMID:38383698)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfc3	ENSDARG00000055969
mus_musculus	Rfc3	ENSMUSG00000033970
rattus_norvegicus	Rfc3	ENSRNOG00000001088
drosophila_melanogaster	RfC38	FBGN0028700
caenorhabditis_elegans		WBGENE00004339

Paralogs (3): RFC2 (ENSG00000049541), RFC5 (ENSG00000111445), RFC4 (ENSG00000163918)

Protein

Protein identifiers

Replication factor C subunit 3 — P40938 (reviewed: P40938)

Alternative names: Activator 1 38 kDa subunit, Activator 1 subunit 3, Replication factor C 38 kDa subunit

All UniProt accessions (2): A0A087X270, P40938

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA.

Subunit / interactions. Subunit of the RFC complex, an heteropentameric complex consisting of a large subunit RFC1 and four small subunits RFC2, RFC3, RFC4 and RFC5; the RFC complex interacts with PCNA. Forms an heterotetrameric complex with RFC2, RFC4 and RFC5; this complex has ATPase activity but is not stimulated by PCNA. The heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 interacts with RAD17. Interacts with CNTD1; this interaction facilitates crossover formation.

Subcellular location. Nucleus.

Similarity. Belongs to the activator 1 small subunits family.

Isoforms (2)

UniProt ID	Names	Canonical?
P40938-1	1	yes
P40938-2	2

RefSeq proteins (2): NP_002906, NP_853536 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR008921	DNA_pol3_clamp-load_cplx_C	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050238	DNA_Rep/Repair_Clamp_Loader	Family

Pfam: PF13177, PF21960, PF22534

Enzyme classification (BRENDA):

• EC 3.6.4.B8 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (40 total): helix 20, strand 11, turn 4, modified residue 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8UMV	ELECTRON MICROSCOPY	2.75
8UMY	ELECTRON MICROSCOPY	2.83
8UMW	ELECTRON MICROSCOPY	2.93
8ZWO	ELECTRON MICROSCOPY	2.99
8UN0	ELECTRON MICROSCOPY	3
8UII	ELECTRON MICROSCOPY	3.04
8UI8	ELECTRON MICROSCOPY	3.1
8UMU	ELECTRON MICROSCOPY	3.16
9IIN	ELECTRON MICROSCOPY	3.2
9UIQ	ELECTRON MICROSCOPY	3.2
8UMT	ELECTRON MICROSCOPY	3.33
8UNJ	ELECTRON MICROSCOPY	3.35
6VVO	ELECTRON MICROSCOPY	3.4
8UI9	ELECTRON MICROSCOPY	3.5
7Z6H	ELECTRON MICROSCOPY	3.59
8UI7	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40938-F1	87.58	0.51

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 (2): 20, 125

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-110312	Translesion synthesis by REV1
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5655862	Translesion synthesis by POLK
R-HSA-5656121	Translesion synthesis by POLI
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69091	Polymerase switching
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9709570	Impaired BRCA2 binding to RAD51

MSigDB gene sets: 388 (showing top): PID_FANCONI_PATHWAY, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GNF2_CKS1B, REACTOME_DNA_REPLICATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, MORF_BUB1, CROONQUIST_NRAS_SIGNALING_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (6): DNA synthesis involved in DNA repair (GO:0000731), DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), DNA strand elongation involved in DNA replication (GO:0006271), DNA repair (GO:0006281), positive regulation of DNA-directed DNA polymerase activity (GO:1900264)

GO Molecular Function (6): DNA binding (GO:0003677), DNA clamp loader activity (GO:0003689), ATP-dependent activity, acting on DNA (GO:0008094), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887), single-stranded DNA helicase activity (GO:0017116)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), DNA replication factor C complex (GO:0005663), Ctf18 RFC-like complex (GO:0031390), chromosome (GO:0005694), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	5
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
G2/M Checkpoints	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
DNA Damage Bypass	1
Telomere C-strand (Lagging Strand) Synthesis	1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
Leading Strand Synthesis	1
Lagging Strand Synthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA biosynthetic process	2
DNA metabolic process	2
DNA replication	2
ATP-dependent activity	2
DNA repair	1
DNA-templated DNA replication	1
DNA strand elongation	1
DNA synthesis involved in DNA replication	1
DNA damage response	1
DNA-directed DNA polymerase activity	1
positive regulation of catalytic activity	1
regulation of transferase activity	1
positive regulation of DNA biosynthetic process	1
nucleic acid binding	1
DNA binding	1
ATP-dependent activity, acting on DNA	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
replication fork	1
protein-containing complex	1
chromosome	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

3174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFC3	RFC2	P32846	992
RFC3	RFC5	P40937	992
RFC3	RFC4	P35249	991
RFC3	CHTF8	P0CG13	970
RFC3	DSCC1	Q9BVC3	962
RFC3	CHTF18	Q8WVB6	960
RFC3	RFC1	P35251	918
RFC3	SMC3	Q9UQE7	811
RFC3	RAD17	O75943	785
RFC3	WAPL	Q7Z5K2	767
RFC3	ESCO1	Q5FWF5	758
RFC3	ESCO2	Q56NI9	743
RFC3	MCM7	P33993	737
RFC3	POLE	Q07864	730
RFC3	PDS5A	Q29RF7	689

IntAct

167 interactions, top by confidence:

A	B	Type	Score
RFC4	RFC5	psi-mi:“MI:0914”(association)	0.950
RFC3	RFC4	psi-mi:“MI:0915”(physical association)	0.860
RFC4	RFC3	psi-mi:“MI:0915”(physical association)	0.860
RFC4	RFC2	psi-mi:“MI:0914”(association)	0.810
RFC2	RFC4	psi-mi:“MI:0915”(physical association)	0.810
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RAD17	RFC4	psi-mi:“MI:0914”(association)	0.730
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC1	RFC4	psi-mi:“MI:0914”(association)	0.710
RFC1	RFC4	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
RFC3	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.560
RFC3	PICK1	psi-mi:“MI:0915”(physical association)	0.560
RFC3	ANKRD40	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS3	RFC3	psi-mi:“MI:0915”(physical association)	0.560
RFC3	INCA1	psi-mi:“MI:0915”(physical association)	0.560
DSCC1	CHTF8	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530

BioGRID (256): RFC3 (Affinity Capture-MS), RFC3 (Affinity Capture-MS), RFC3 (Affinity Capture-MS), RFC2 (Co-fractionation), RFC3 (Co-fractionation), RFC3 (Co-fractionation), RFC4 (Co-fractionation), RFC5 (Co-fractionation), RFC3 (Affinity Capture-MS), RFC3 (Affinity Capture-Western), RFC3 (Affinity Capture-Western), RFC3 (Affinity Capture-Western), RFC3 (Affinity Capture-MS), RFC3 (Affinity Capture-MS), RFC3 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A2VE14, A5PLN9, A7MB76, A7YWS7, D3K5L7, E1C6Q1, E2R222, O35345, O54865, O60684, O70133, O94973, P16068, P17427, P18484, P20595, P40938, P97834, Q02153, Q08211, Q0V7M0, Q0VCK5, Q0VFT9, Q13042, Q13098, Q15645, Q28141, Q2TBV1, Q3TIR1, Q3UA06, Q4ZHR9, Q503E9, Q5M887, Q5R874, Q5RBV0, Q5RCG0, Q5XHZ9, Q5ZHN3, Q5ZKQ6

Diamond homologs: A0B6D7, A1RSA2, A1RV38, A1RWU7, A2SQT3, A3CUX9, A3DNV9, A3MS28, A4FZ74, A4WGV2, A4WLY0, A5UMF3, A5UMF4, A6US36, A6VJ61, A7I781, A7I8Y0, A9A6K6, B0R7H7, B9LPV1, O14003, O26342, O26343, O28219, O57852, O57853, O74111, O94449, O94697, P0C7N7, P34429, P35249, P35250, P38251, P38629, P40339, P40348, P40937, P40938, P53016

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RFC3	“form complex”	“RF-C complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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
Translesion synthesis by REV1	5	40.5×	2e-05
Translesion synthesis by POLI	5	38.2×	2e-05
Translesion synthesis by POLK	5	36.0×	2e-05
Translesion Synthesis by POLH	5	34.1×	2e-05
Polymerase switching on the C-strand of the telomere	6	28.8×	1e-05
Gap-filling DNA repair synthesis and ligation in GG-NER	5	25.0×	8e-05
Activation of ATR in response to replication stress	7	23.9×	9e-06
Recognition of DNA damage by PCNA-containing replication complex	5	21.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	6	11.1×	3e-03
mRNA splicing, via spliceosome	9	6.7×	2e-03
DNA repair	12	6.2×	2e-04
DNA damage response	11	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1473 predictions. Top by Δscore:

Variant	Effect	Δscore
13:33818261:ACCTG:A	donor_gain	1.0000
13:33818262:CCTG:C	donor_gain	1.0000
13:33818263:CTG:C	donor_gain	1.0000
13:33818263:CTGGT:C	donor_loss	1.0000
13:33818264:TG:T	donor_gain	1.0000
13:33818265:GG:G	donor_gain	1.0000
13:33818265:GGT:G	donor_loss	1.0000
13:33818266:G:GG	donor_gain	1.0000
13:33818266:GTGA:G	donor_loss	1.0000
13:33818267:T:G	donor_loss	1.0000
13:33821127:TTCA:T	acceptor_loss	1.0000
13:33821128:TCA:T	acceptor_loss	1.0000
13:33821227:TGTTG:T	donor_gain	1.0000
13:33821228:GTTGG:G	donor_gain	1.0000
13:33821265:TCACA:T	donor_gain	1.0000
13:33821266:CACA:C	donor_gain	1.0000
13:33821267:ACA:A	donor_gain	1.0000
13:33821268:CA:C	donor_gain	1.0000
13:33821270:G:GG	donor_gain	1.0000
13:33821270:GTAAG:G	donor_loss	1.0000
13:33821271:T:A	donor_loss	1.0000
13:33823908:T:TA	acceptor_gain	1.0000
13:33823911:CCACA:C	acceptor_loss	1.0000
13:33823914:C:G	acceptor_gain	1.0000
13:33823914:CA:C	acceptor_loss	1.0000
13:33823915:A:AG	acceptor_gain	1.0000
13:33823916:G:GT	acceptor_gain	1.0000
13:33823916:GA:G	acceptor_gain	1.0000
13:33823916:GAC:G	acceptor_gain	1.0000
13:33823916:GACT:G	acceptor_gain	1.0000

AlphaMissense

2332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:33821169:G:A	G42E	1.000
13:33829977:G:C	R178T	1.000
13:33829977:G:T	R178M	1.000
13:33831296:T:A	W251R	1.000
13:33831296:T:C	W251R	1.000
13:33821157:T:C	L38P	0.999
13:33821168:G:A	G42R	0.999
13:33821168:G:C	G42R	0.999
13:33821169:G:T	G42V	0.999
13:33821184:G:A	G47E	0.999
13:33823956:A:C	S89R	0.999
13:33823957:G:T	S89I	0.999
13:33823958:T:A	S89R	0.999
13:33823958:T:G	S89R	0.999
13:33823965:C:G	H92D	0.999
13:33829863:T:C	L140P	0.999
13:33829875:C:A	A144D	0.999
13:33829879:G:C	Q145H	0.999
13:33829879:G:T	Q145H	0.999
13:33829884:C:A	A147D	0.999
13:33829887:T:C	L148S	0.999
13:33829893:G:C	R150T	0.999
13:33829894:A:C	R150S	0.999
13:33829894:A:T	R150S	0.999
13:33829901:G:A	E153K	0.999
13:33829902:A:T	E153V	0.999
13:33829903:A:C	E153D	0.999
13:33829903:A:T	E153D	0.999
13:33829923:G:C	R160T	0.999
13:33829924:A:C	R160S	0.999

dbSNP variants (sampled 300 via entrez): RS1000020361 (13:33838625 T>C), RS1000027154 (13:33921504 C>T), RS1000058149 (13:33921305 A>C), RS1000058469 (13:33952455 T>G), RS1000074457 (13:33968737 C>T), RS1000083276 (13:33903421 C>G), RS1000105300 (13:33968788 A>G), RS1000112227 (13:33925644 A>G), RS1000120882 (13:33897075 G>A), RS1000123527 (13:33926667 T>C), RS1000130395 (13:33961611 G>C), RS1000131321 (13:33918893 T>A), RS1000136394 (13:33969088 G>A,T), RS1000140918 (13:33886152 G>C), RS1000172467 (13:33828378 C>A)

Disease associations

OMIM: gene MIM:600405 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000484_4	Alzheimer’s disease	6.000000e-07
GCST001762_414	Obesity-related traits	3.000000e-06
GCST001762_895	Obesity-related traits	3.000000e-06
GCST007856_78	Colorectal cancer or advanced adenoma	3.000000e-07
GCST010397_106	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725144 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.44	Kd	36	nM	MOLIBRESIB
7.30	Kd	50.52	nM	CHEMBL5653589
7.30	ED50	50.52	nM	CHEMBL5653589
7.05	IC50	90	nM	MOLIBRESIB
6.32	Kd	484.7	nM	CHEMBL3752910
6.32	ED50	484.7	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179104: Binding affinity against RFC3 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0360	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149219: Binding affinity to human RFC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0505	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149219: Binding affinity to human RFC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.4847	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Valproic Acid	increases expression, affects expression, decreases expression	3
Cyclosporine	decreases expression	3
bisphenol A	decreases expression	2
Irinotecan	decreases expression, increases response to substance	2
Cannabidiol	increases expression, decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Oxygen	decreases expression	2
Testosterone	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
riddelliine	decreases expression, increases metabolic processing	1
arsenite	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652261	Binding	Binding affinity to human RFC3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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