RHOXF1

Summary

RHOXF1 (Rhox homeobox family member 1, HGNC:29993) is a protein-coding gene on chromosome Xq24, encoding Rhox homeobox family member 1 (Q8NHV9). Transcription factor maybe involved in reproductive processes.

This gene is a member of the PEPP subfamily of paired-like homoebox genes. The gene may be regulated by androgens and epigenetic mechanisms. The encoded nuclear protein is likely a transcription factor that may play a role in human reproduction.

Source: NCBI Gene 158800 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure (Moderate, GenCC)
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_139282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29993
Approved symbol	RHOXF1
Name	Rhox homeobox family member 1
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	OTEX, PEPP1
Ensembl gene	ENSG00000101883
Ensembl biotype	protein_coding
OMIM	300446
Entrez	158800

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000217999, ENST00000422226, ENST00000555168, ENST00000701130, ENST00000701644, ENST00000703667, ENST00000956250, ENST00000956251

RefSeq mRNA: 1 — MANE Select: NM_139282 NM_139282

CCDS: CCDS14593

Canonical transcript exons

ENST00000217999 — 3 exons

Exon	Start	End
ENSE00000675731	120112869	120112914
ENSE00000675733	120115465	120115913
ENSE00001187848	120109051	120109302

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 92.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0229 / max 18.9456, expressed in 5 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200333	0.0086	4
200334	0.0082	3
200335	0.0062	3

Top tissues by expression

238 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	92.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.24	gold quality
right testis	UBERON:0004534	81.43	gold quality
left testis	UBERON:0004533	80.88	gold quality
testis	UBERON:0000473	79.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.22	gold quality
right uterine tube	UBERON:0001302	76.35	gold quality
cerebellar hemisphere	UBERON:0002245	75.48	gold quality
cerebellar cortex	UBERON:0002129	75.24	gold quality
cerebellum	UBERON:0002037	73.40	gold quality
granulocyte	CL:0000094	70.20	gold quality
right ovary	UBERON:0002118	66.12	gold quality
right frontal lobe	UBERON:0002810	65.97	gold quality
left ovary	UBERON:0002119	65.31	gold quality
Brodmann (1909) area 23	UBERON:0013554	63.63	silver quality
right adrenal gland cortex	UBERON:0035827	63.38	gold quality
adipose tissue	UBERON:0001013	62.96	gold quality
hypothalamus	UBERON:0001898	62.81	gold quality
ovary	UBERON:0000992	62.73	gold quality
left uterine tube	UBERON:0001303	62.50	gold quality
metanephros cortex	UBERON:0010533	62.40	gold quality
middle temporal gyrus	UBERON:0002771	62.29	gold quality
adult organism	UBERON:0007023	62.14	gold quality
lower esophagus	UBERON:0013473	62.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.89	gold quality
skin of hip	UBERON:0001554	61.48	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.10	gold quality
primary visual cortex	UBERON:0002436	61.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.19
E-ANND-3	no	0.96

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BCL2	Activation

JASPAR motifs

Motif	Name	Family
MA0719.1	RHOXF1	Paired-related HD factors
MA0719.2	RHOXF1	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:18585360

miRNA regulators (miRDB)

16 targeting RHOXF1, 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-4803	99.98	71.99	3117
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-6888-5P	95.89	63.78	831

Literature-anchored findings (GeneRIF, showing 2)

• cloning and characterization of human OTEX (PMID:11980563)
• Deleterious variants in X-linked RHOXF1 cause male infertility with oligo- and azoospermia. (PMID:38258527)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rhox13	ENSMUSG00000050197
rattus_norvegicus	Rhox13	ENSRNOG00000028050

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), 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), SHOX (ENSG00000185960)

Protein

Protein identifiers

Rhox homeobox family member 1 — Q8NHV9 (reviewed: Q8NHV9)

Alternative names: Ovary-, testis- and epididymis-expressed gene protein, Paired-like homeobox protein PEPP-1

All UniProt accessions (1): Q8NHV9

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.

Subunit / interactions. Does not interact with itself.

Subcellular location. Nucleus.

Tissue specificity. Ovary, testis and epididymis. Also detected in the prostate and the mammary gland. Expressed in many tumor cell lines derived from acute lymphocytic leukemia, prostate, endometrial adenocarcinoma, melanoma, bladder carcinoma, colon carcinoma, erythroleukemia and breast carcinoma. Not expressed in placenta. In testis, mainly expressed in germ cells, but also detected in somatic cells such as Sertoli cells, Leydig cells and peritubular cells.

Domain organisation. Mutagenesis of amino acids 147 to 164 and 155 to 164 lead to a major cytoplasmic localization, with only minor localization in the nucleus.

Induction. By androgen.

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

RefSeq proteins (1): NP_644811* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050649	Paired_Homeobox_TFs	Family

Pfam: PF00046

UniProt features (11 total): sequence variant 6, chain 1, DNA-binding region 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHV9-F1	65.63	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEUROGENESIS, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, CONRAD_STEM_CELL, GOBP_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXq24, MADAN_DPPA4_TARGETS

GO Biological Process (5): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), androgen receptor signaling pathway (GO:0030521), neuron development (GO:0048666)

GO Molecular Function (6): 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), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of gene expression	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
nuclear receptor-mediated steroid hormone signaling pathway	1
neuron differentiation	1
cell development	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
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOXF1	AR	P10275	523
RHOXF1	UNC5C	O95185	462
RHOXF1	ZNF354C	Q86Y25	449
RHOXF1	PLTP	P55058	353
RHOXF1	GDAP1	Q8TB36	353
RHOXF1	FBXO39	Q8N4B4	330
RHOXF1	TGIF2LX	Q8IUE1	328
RHOXF1	DCAF4L1	Q3SXM0	324
RHOXF1	DPRX	A6NFQ7	321
RHOXF1	ZSCAN1	Q8NBB4	320
RHOXF1	PAGE2B	Q5JRK9	302
RHOXF1	D6RAR5	D6RAR5	301
RHOXF1	MZF1	P28698	297
RHOXF1	VCX3B	Q9H321	297
RHOXF1	ZNF502	Q8TBZ5	290

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RHOXF1	MAP1LC3C	psi-mi:“MI:0915”(physical association)	0.560
NPAS2	RHOXF1	psi-mi:“MI:0915”(physical association)	0.370
RHOXF1	VTN	psi-mi:“MI:0915”(physical association)	0.370
RHOXF1	MAP1LC3C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): MAP1LC3C (Two-hybrid), RHOXF1 (Positive Genetic), RHOXF1 (Two-hybrid), VTN (Two-hybrid)

ESM2 similar proteins: A0A1W2PPF3, A0A3B3IT52, E9Q3T6, O02747, O13161, O42173, O57374, O73622, O95238, P01103, P01104, P09632, P0C7M4, P10242, P14837, P17278, P30561, P31538, P41738, P46200, Q1KKS8, Q28G02, Q32NH9, Q4JM65, Q5REX1, Q5WM45, Q66IG8, Q68EH7, Q6U8D7, Q6ZTZ1, Q7T1K4, Q8BIL2, Q8BKE5, Q8CFH6, Q8IWB6, Q8JIT7, Q8NHV9, Q8R4S2, Q8R4S4, Q8R4S5

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

1 interactions.

A	Effect	B	Mechanism
RHOXF1	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

680 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120112773:TTAGA:T	donor_gain	1.0000
X:120112910:CCCTT:C	acceptor_gain	1.0000
X:120112911:CCTTC:C	acceptor_gain	1.0000
X:120159414:G:GG	donor_gain	1.0000
X:120159424:GCG:G	donor_gain	1.0000
X:120159427:GTA:G	donor_loss	1.0000
X:120159428:T:A	donor_loss	1.0000
X:120163449:T:A	acceptor_gain	1.0000
X:120112791:AG:A	donor_gain	0.9900
X:120112912:CTT:C	acceptor_gain	0.9900
X:120112913:TT:T	acceptor_gain	0.9900
X:120112915:C:CC	acceptor_gain	0.9900
X:120115460:CTTA:C	donor_loss	0.9900
X:120115461:TTA:T	donor_loss	0.9900
X:120115462:TA:T	donor_loss	0.9900
X:120115463:A:AC	donor_gain	0.9900
X:120115463:A:C	donor_loss	0.9900
X:120115464:C:CC	donor_gain	0.9900
X:120115507:T:A	donor_gain	0.9900
X:120159427:G:GG	donor_gain	0.9900
X:120163453:T:A	acceptor_gain	0.9900
X:120163456:A:AG	acceptor_gain	0.9900
X:120163457:G:GG	acceptor_gain	0.9900
X:120163457:GATTT:G	acceptor_gain	0.9900
X:120109298:CAAAC:C	acceptor_gain	0.9800
X:120109300:AAC:A	acceptor_gain	0.9800
X:120109301:ACCTA:A	acceptor_loss	0.9800
X:120109302:CCTAC:C	acceptor_loss	0.9800
X:120109303:C:CC	acceptor_gain	0.9800
X:120109303:CTAC:C	acceptor_loss	0.9800

AlphaMissense

1205 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120109294:A:C	F151L	0.999
X:120109294:A:T	F151L	0.999
X:120109296:A:G	F151L	0.999
X:120115497:G:C	F122L	0.999
X:120115497:G:T	F122L	0.999
X:120115499:A:G	F122L	0.999
X:120109295:A:G	F151S	0.997
X:120115533:G:C	F110L	0.997
X:120115533:G:T	F110L	0.997
X:120115535:A:G	F110L	0.997
X:120115483:T:C	Y127C	0.996
X:120115498:A:G	F122S	0.996
X:120109282:C:A	R155S	0.995
X:120109282:C:G	R155S	0.995
X:120112903:G:T	A137D	0.995
X:120115534:A:C	F110C	0.995
X:120115481:G:A	P128S	0.994
X:120115499:A:C	F122V	0.994
X:120115534:A:G	F110S	0.994
X:120109296:A:T	F151I	0.993
X:120115498:A:C	F122C	0.993
X:120115499:A:T	F122I	0.993
X:120109295:A:C	F151C	0.992
X:120109296:A:C	F151V	0.992
X:120109270:C:A	R159S	0.991
X:120109270:C:G	R159S	0.991
X:120112904:C:G	A137P	0.991
X:120115480:G:T	P128H	0.991
X:120115510:A:G	L118P	0.990
X:120109285:T:A	K154N	0.989

dbSNP variants (sampled 300 via entrez): RS1000927824 (X:120120963 G>A,T), RS1001155981 (X:120111814 T>C), RS1001599870 (X:120116858 G>A), RS1002051265 (X:120119349 A>G), RS1002114263 (X:120117228 C>A), RS1002221084 (X:120110309 G>A), RS1002336556 (X:120119004 G>T), RS1002713821 (X:120115275 C>A), RS1004397492 (X:120119576 C>G), RS1004940043 (X:120112735 T>C,G), RS1005515651 (X:120117617 C>A), RS1005661828 (X:120108667 A>G), RS1006154703 (X:120108997 A>G), RS1006413099 (X:120110375 C>T), RS1008432815 (X:120120556 C>T)

Disease associations

OMIM: gene MIM:300446 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure	Moderate	X-linked

Mondo (1): spermatogenic failure (MONDO:0004983)

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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Decitabine	increases expression	1
Arsenic	affects methylation	1
Estradiol	decreases expression	1
Lead	increases expression	1
Malathion	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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