RFX8

Summary

RFX8 (regulatory factor X8, HGNC:37253) is a protein-coding gene on chromosome 2q11.2, encoding DNA-binding protein RFX8 (Q6ZV50). May be a transcription factor.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 731220 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_001145664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37253
Approved symbol	RFX8
Name	regulatory factor X8
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ42986
Ensembl gene	ENSG00000196460
Ensembl biotype	protein_coding
Entrez	731220

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000428343, ENST00000481179, ENST00000484091, ENST00000492238, ENST00000646446, ENST00000646893, ENST00000939864

RefSeq mRNA: 4 — MANE Select: NM_001145664 NM_001145664, NM_001367508, NM_001367509, NM_001367510

CCDS: CCDS46376

Canonical transcript exons

ENST00000428343 — 12 exons

Exon	Start	End
ENSE00001471808	101421724	101421777
ENSE00001756204	101414854	101414912
ENSE00003480590	101405943	101406057
ENSE00003518179	101402436	101402752
ENSE00003559003	101410619	101410713
ENSE00003581494	101412915	101413071
ENSE00003605685	101422362	101422472
ENSE00003676652	101418851	101418964
ENSE00003679552	101466777	101466900
ENSE00003694337	101417534	101417684
ENSE00003844077	101474636	101475112
ENSE00003850912	101397359	101397724

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 82.85.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2479 / max 77.3136, expressed in 494 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29955	0.9763	359
29952	0.7812	329
29953	0.1815	100
29956	0.1569	78
29954	0.1520	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.85	gold quality
bone marrow	UBERON:0002371	72.16	gold quality
thoracic mammary gland	UBERON:0005200	69.60	gold quality
tibial nerve	UBERON:0001323	69.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.82	gold quality
adipose tissue	UBERON:0001013	65.62	gold quality
superior frontal gyrus	UBERON:0002661	65.24	gold quality
bone marrow cell	CL:0002092	65.20	silver quality
islet of Langerhans	UBERON:0000006	64.91	gold quality
sural nerve	UBERON:0015488	64.34	gold quality
omental fat pad	UBERON:0010414	64.17	gold quality
prefrontal cortex	UBERON:0000451	63.94	gold quality
testis	UBERON:0000473	62.76	gold quality
frontal cortex	UBERON:0001870	62.69	gold quality
primary visual cortex	UBERON:0002436	62.23	gold quality
left testis	UBERON:0004533	62.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.16	gold quality
right testis	UBERON:0004534	62.16	gold quality
placenta	UBERON:0001987	61.88	gold quality
stromal cell of endometrium	CL:0002255	61.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.24	gold quality
skin of abdomen	UBERON:0001416	61.03	gold quality
skin of leg	UBERON:0001511	60.92	gold quality
zone of skin	UBERON:0000014	60.90	gold quality
right frontal lobe	UBERON:0002810	60.64	gold quality
cerebral cortex	UBERON:0000956	59.99	gold quality
smooth muscle tissue	UBERON:0001135	59.70	gold quality
descending thoracic aorta	UBERON:0002345	59.25	gold quality
left uterine tube	UBERON:0001303	58.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting RFX8, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-217-3P	95.67	68.42	1000

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rfx8	ENSMUSG00000057173
rattus_norvegicus	Rfx8	ENSRNOG00000058243
caenorhabditis_elegans		WBGENE00000914

Paralogs (7): RFX3 (ENSG00000080298), RFX2 (ENSG00000087903), RFX4 (ENSG00000111783), RFX1 (ENSG00000132005), RFX5 (ENSG00000143390), RFX7 (ENSG00000181827), RFX6 (ENSG00000185002)

Protein

Protein identifiers

DNA-binding protein RFX8 — Q6ZV50 (reviewed: Q6ZV50)

Alternative names: Regulatory factor X 8

All UniProt accessions (5): A0A2R8Y560, A0A2R8YED2, D6RAX4, E9PDA6, Q6ZV50

UniProt curated annotations — full annotation on UniProt →

Function. May be a transcription factor.

Subcellular location. Nucleus.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the RFX family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZV50-1	1	yes
Q6ZV50-2	2
Q6ZV50-3	3

RefSeq proteins (4): NP_001139136, NP_001354437, NP_001354438, NP_001354439 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003150	DNA-bd_RFX	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039779	RFX-like	Family
IPR057321	RFX1-4/6/8-like_BCD	Domain

Pfam: PF02257, PF25340

UniProt features (10 total): splice variant 5, sequence conflict 3, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZV50-F1	71.29	0.30

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): CAGCTG_AP4_Q5, HEN1_01, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, chr2q11, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, S8_01, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MAFG_TARGET_GENES, MIR519E_5P, MIR515_5P, MIR221_3P, MIR222_3P, MIR217_3P, GSE16522_ANTI_CD3CD28_STIM_VS_UNSTIM_NAIVE_CD8_TCELL_UP, CEBPGAMMA_Q6

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFX8	RFX7	Q2KHR2	606
RFX8	RFX5	P48382	557
RFX8	LENG1	Q96BZ8	553
RFX8	LLPH	Q9BRT6	528
RFX8	TUSC1	Q2TAM9	486
RFX8	PDAP1	Q13442	463
RFX8	KRT85	P78386	462
RFX8	ACSS3	Q9H6R3	460
RFX8	LRRTM4	Q86VH4	457
RFX8	PIGQ	Q9BRB3	453
RFX8	SMIM15	Q7Z3B0	440
RFX8	THOC1	Q96FV9	438
RFX8	MSRB3	Q8IXL7	438
RFX8	FAM228A	Q86W67	430
RFX8	ZMYM3	Q14202	416
RFX8	OR14C36	Q8NHC7	416

IntAct

0 interactions, top by confidence:

BioGRID (1): RFX8 (Affinity Capture-MS)

ESM2 similar proteins: A2BGP7, A2CJ06, A6H5X4, A7E316, E2RSS3, F7BHS0, O35144, O55036, P0DOV1, Q13342, Q1LX29, Q2HJ93, Q3B7D9, Q3TD16, Q3U827, Q5I0E2, Q5I0J8, Q5NBU8, Q5RCZ8, Q5XFX8, Q60953, Q66JT0, Q6AXZ2, Q6AZF8, Q6IE82, Q6IRU7, Q6ZQF7, Q6ZV50, Q7TNY7, Q80VH0, Q8BP86, Q8BVK9, Q8BVM9, Q8C0G2, Q8C0V1, Q8C267, Q8CGE8, Q8K2H3, Q8NDB2, Q91YK2

Diamond homologs: A0A1L8GWK2, A0A1L8H0H2, A0JMF8, A2BGA0, A6QLW9, B1WAV2, B2GV50, D2HNW6, D3YU81, F8VPJ6, P22670, P48377, P48378, P48379, P48380, P48381, P48382, P48383, P48743, Q09555, Q0V9K5, Q2KHR2, Q32NR3, Q33E94, Q4R3I8, Q4R3Z4, Q59V88, Q5EAP5, Q5RDR2, Q5RJA1, Q6ZV50, Q7TNK1, Q8C7R7, Q8HWS3, Q9JL61, Q5AMQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2646 predictions. Top by Δscore:

Variant	Effect	Δscore
2:101452443:CAAG:C	acceptor_gain	1.0000
2:101466772:CTTA:C	donor_loss	1.0000
2:101466773:TTA:T	donor_loss	1.0000
2:101466774:TA:T	donor_loss	1.0000
2:101466775:A:AC	donor_gain	1.0000
2:101466775:AC:A	donor_gain	1.0000
2:101466775:ACCTT:A	donor_gain	1.0000
2:101466776:C:CC	donor_gain	1.0000
2:101466776:C:CG	donor_loss	1.0000
2:101466776:CC:C	donor_gain	1.0000
2:101466776:CCTT:C	donor_gain	1.0000
2:101466776:CCTTC:C	donor_gain	1.0000
2:101466896:CCAAC:C	acceptor_gain	1.0000
2:101466897:CAAC:C	acceptor_gain	1.0000
2:101466897:CAACC:C	acceptor_gain	1.0000
2:101466898:AAC:A	acceptor_gain	1.0000
2:101466898:AACCT:A	acceptor_loss	1.0000
2:101466899:AC:A	acceptor_gain	1.0000
2:101466900:CC:C	acceptor_gain	1.0000
2:101466900:CCT:C	acceptor_loss	1.0000
2:101466901:CT:C	acceptor_loss	1.0000
2:101466902:T:A	acceptor_loss	1.0000
2:101474634:ACAC:A	donor_gain	1.0000
2:101474635:CA:C	donor_gain	1.0000
2:101474635:CACC:C	donor_gain	1.0000
2:101474635:CACCT:C	donor_gain	1.0000
2:101397721:TGAG:T	acceptor_gain	0.9900
2:101397725:C:CC	acceptor_gain	0.9900
2:101406069:T:C	acceptor_gain	0.9900
2:101406069:T:TC	acceptor_gain	0.9900

AlphaMissense

3139 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012656 (2:101460689 G>A), RS1000038474 (2:101435113 C>T), RS1000079067 (2:101454935 C>A), RS1000102539 (2:101441396 G>A), RS1000141999 (2:101462442 G>T), RS1000184025 (2:101429372 A>G), RS1000256925 (2:101435363 C>G), RS1000262555 (2:101476337 T>G), RS1000289402 (2:101441172 G>A), RS1000294870 (2:101442591 T>C,G), RS1000314058 (2:101424097 G>T), RS1000330497 (2:101442220 G>A), RS1000371318 (2:101470829 C>T), RS1000380647 (2:101402748 G>A), RS1000407630 (2:101423906 T>A)

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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol A	increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	decreases expression	1
Dexamethasone	decreases expression	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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