RHOXF2B

Summary

RHOXF2B (Rhox homeobox family member 2B, HGNC:33519) is a protein-coding gene on chromosome Xq24, encoding Rhox homeobox family member 2B (P0C7M4). Transcription factor maybe involved in reproductive processes.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in positive regulation of gene expression. Predicted to be located in chromatin.

Source: NCBI Gene 727940 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001099685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33519
Approved symbol	RHOXF2B
Name	Rhox homeobox family member 2B
Location	Xq24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203989
Ensembl biotype	protein_coding
Entrez	727940

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371402

RefSeq mRNA: 1 — MANE Select: NM_001099685 NM_001099685

CCDS: CCDS43985

Canonical transcript exons

ENST00000371402 — 4 exons

Exon	Start	End
ENSE00001594748	120076877	120077288
ENSE00001605304	120075900	120075945
ENSE00001642029	120077474	120077690
ENSE00001747102	120072264	120072845

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 94.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6132 / max 59.7410, expressed in 55 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209796	0.6132	55

Top tissues by expression

102 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	94.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.75	gold quality
right testis	UBERON:0004534	89.48	gold quality
testis	UBERON:0000473	88.94	gold quality
left testis	UBERON:0004533	88.70	gold quality
bone marrow cell	CL:0002092	43.77	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
bone marrow	UBERON:0002371	36.81	gold quality
liver	UBERON:0002107	36.70	gold quality
skeletal muscle tissue	UBERON:0001134	36.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.56	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right ovary	UBERON:0002118	35.98	silver quality
ovary	UBERON:0000992	35.59	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
blood	UBERON:0000178	35.33	gold quality
gastrocnemius	UBERON:0001388	35.15	gold quality
left ovary	UBERON:0002119	35.01	silver quality
muscle of leg	UBERON:0001383	34.68	gold quality
heart left ventricle	UBERON:0002084	34.02	gold quality
muscle tissue	UBERON:0002385	33.47	gold quality
right adrenal gland	UBERON:0001233	32.27	gold quality
mucosa of stomach	UBERON:0001199	31.86	gold quality
multicellular organism	UBERON:0000468	31.82	gold quality
heart	UBERON:0000948	31.35	gold quality
pancreas	UBERON:0001264	31.08	gold quality
body of pancreas	UBERON:0001150	30.95	gold quality
left adrenal gland	UBERON:0001234	30.95	gold quality
fundus of stomach	UBERON:0001160	30.81	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.80
E-ANND-3	no	1.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting RHOXF2B, 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-8485	100.00	77.57	4731
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-606	98.72	67.34	960
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-18B-3P	98.05	65.55	595
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-3157-3P	95.86	67.08	454
HSA-MIR-31-3P	95.17	69.82	575
HSA-MIR-371B-3P	94.48	66.59	345

Cross-species orthologs

0 orthologs

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155)

Protein

Protein identifiers

Rhox homeobox family member 2B — P0C7M4 (reviewed: P0C7M4)

All UniProt accessions (1): P0C7M4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor maybe involved in reproductive processes. Modulates expression of target genes encoding proteins involved in processes relevant to spermatogenesis.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis, mainly expressed in germ cells, but also detected in somatic cells such as Sertoli cells, Leydig cells and peritubular cells.

Similarity. Belongs to the paired-like homeobox family. PEPP subfamily.

RefSeq proteins (1): NP_001093155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF00046

UniProt features (10 total): sequence variant 4, compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7M4-F1	63.61	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GOBP_NEUROGENESIS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXq24, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, DELACROIX_RAR_BOUND_ES, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR1468_3P, MIR5003_3P, MIR3128, MIR149_5P, MIR31_3P, MIR18B_3P, MIR424_3P, GOBP_POSITIVE_REGULATION_OF_GENE_EXPRESSION, GOBP_GENERATION_OF_NEURONS

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), neuron development (GO:0048666), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677)

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 gene expression	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
neuron differentiation	1
cell development	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOXF2B	TPRX1	Q8N7U7	570
RHOXF2B	DPRX	A6NFQ7	506
RHOXF2B	ARGFX	A6NJG6	497
RHOXF2B	DUXB	A0A1W2PPF3	490
RHOXF2B	NANOGNB	Q7Z5D8	480
RHOXF2B	TGIF2LX	Q8IUE1	476
RHOXF2B	DUXA	A6NLW8	448
RHOXF2B	D6RAR5	D6RAR5	388
RHOXF2B	UNC5C	O95185	387
RHOXF2B	NKAP	Q8N5F7	370
RHOXF2B	INHA	P05111	349
RHOXF2B	SPATA3	Q8NHX4	349
RHOXF2B	SEBOX	Q9HB31	348
RHOXF2B	ANHX	E9PGG2	342
RHOXF2B	LEUTX	A8MZ59	337

IntAct

0 interactions, top by confidence:

BioGRID (1): RHOXF2B (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPF3, A0A1W2PPM1, A1A546, A1YGI6, A2T763, A5YC49, A6NFQ7, A6NJG6, D2HQI1, G3X9P6, O42173, O57374, P09632, P0C7M4, P10242, P14837, P17278, P31272, P31538, Q1KKS8, Q28ET4, Q28G02, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5W1J6, Q68EH7, Q6NSW7, Q80Z64, Q8IUE1, Q8JH55, Q8JIT7, Q8JJ26, Q8MIB7, Q8MIB8, Q8MIE9, Q91685

Diamond homologs: A1A546, A1YEV8, A1YEY5, A1YFI3, A1YG25, A1YG57, A2T711, A2T733, A2T7P4, A6NNA5, A6YP92, F6YCR7, G5EC89, G5EDS1, O14813, O18400, O35085, O35137, O35160, O35602, O35690, O42115, O42201, O42356, O42357, O42358, O42567, O43186, O54751, O70137, O73917, O75360, O75364, O88436, O93385, O95076, O97039, P06601, P0C7M4, P26367

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

466 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120072853:C:CT	acceptor_gain	1.0000
X:120072854:A:T	acceptor_gain	1.0000
X:120076876:CCG:C	donor_gain	1.0000
X:120076888:A:AC	donor_gain	1.0000
X:120076889:C:CC	donor_gain	1.0000
X:120072841:CAAAT:C	acceptor_gain	0.9900
X:120072846:C:CC	acceptor_gain	0.9900
X:120072850:A:T	acceptor_gain	0.9900
X:120076870:GGCTT:G	donor_loss	0.9900
X:120076871:GCTT:G	donor_loss	0.9900
X:120076872:CTT:C	donor_loss	0.9900
X:120076873:TTA:T	donor_loss	0.9900
X:120076874:TACCG:T	donor_loss	0.9900
X:120076875:A:AC	donor_gain	0.9900
X:120076876:C:CC	donor_gain	0.9900
X:120072844:ATCT:A	acceptor_loss	0.9800
X:120072845:TCT:T	acceptor_loss	0.9800
X:120072846:C:CA	acceptor_loss	0.9800
X:120072849:C:CT	acceptor_gain	0.9800
X:120077472:AC:A	donor_gain	0.9800
X:120077473:CC:C	donor_gain	0.9800
X:120072843:AAT:A	acceptor_gain	0.9700
X:120075946:C:CC	acceptor_gain	0.9700
X:120075667:T:C	donor_gain	0.9600
X:120072844:AT:A	acceptor_gain	0.9500
X:120072842:AAAT:A	acceptor_gain	0.9400
X:120072844:ATCTT:A	acceptor_gain	0.9300
X:120074572:AGTGC:A	donor_gain	0.9300
X:120075666:A:AC	donor_gain	0.9300
X:120072845:TCTTC:T	acceptor_gain	0.9200

AlphaMissense

1919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120072837:A:C	F182L	0.994
X:120072837:A:T	F182L	0.994
X:120072839:A:G	F182L	0.994
X:120076909:G:C	F153L	0.991
X:120076909:G:T	F153L	0.991
X:120076911:A:G	F153L	0.991
X:120076945:G:C	F141L	0.991
X:120076945:G:T	F141L	0.991
X:120076947:A:G	F141L	0.991
X:120072825:T:A	R186S	0.985
X:120072825:T:G	R186S	0.985
X:120072838:A:G	F182S	0.980
X:120076894:G:C	F158L	0.978
X:120076894:G:T	F158L	0.978
X:120076896:A:G	F158L	0.978
X:120076910:A:G	F153S	0.978
X:120076946:A:C	F141C	0.976
X:120072828:T:A	R185S	0.974
X:120072828:T:G	R185S	0.974
X:120072838:A:C	F182C	0.973
X:120076910:A:C	F153C	0.973
X:120076931:A:G	L146P	0.971
X:120076946:A:G	F141S	0.970
X:120072826:C:G	R186T	0.969
X:120076922:A:G	L149P	0.966
X:120072813:C:A	R190S	0.965
X:120072813:C:G	R190S	0.965
X:120072839:A:T	F182I	0.958
X:120076933:C:A	Q145H	0.958
X:120076933:C:G	Q145H	0.958

dbSNP variants (sampled 300 via entrez): RS112514689 (X:120078252 C>A,G), RS1157028494 (X:120078205 TTTTCTTTCTTTC>T,TTTTC,TTTTCTTTC,TTTTCTTTCTTTCTTTC), RS1157142630 (X:120075908 C>A,T), RS1158390261 (X:120075286 C>A), RS1158505991 (X:120073451 T>C), RS1159669051 (X:120074313 T>A), RS1160639641 (X:120077938 A>G), RS1163397537 (X:120077068 G>A,C), RS1163414586 (X:120075438 T>C), RS1164269883 (X:120074538 T>G), RS1164654176 (X:120073669 C>T), RS1165310975 (X:120074523 T>C), RS1167887648 (X:120075675 T>C), RS1168002778 (X:120073893 T>C), RS1169222092 (X:120073702 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:300257

GenCC curated gene-disease

Mondo (1): Danon disease (MONDO:0010281)

Orphanet (1): Danon disease (Orphanet:34587)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D052120	Glycogen Storage Disease Type IIb	C10.597.606.360.455.562; C14.280.238.458; C16.320.322.201; C16.320.565.202.449.510; C18.452.648.202.449.510

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06092034	PHASE2	RECRUITING	A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease
NCT03882437	PHASE1	UNKNOWN	Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B
NCT03766386	Not specified	UNKNOWN	The Natural History of Danon Disease
NCT05548855	Not specified	COMPLETED	Natural History of Danon Disease
NCT06214507	Not specified	RECRUITING	Danon Disease Natural History Study
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques