RHOF

Summary

RHOF (ras homolog family member F, filopodia associated, HGNC:15703) is a protein-coding gene on chromosome 12q24.31, encoding Rho-related GTP-binding protein RhoF (Q9HBH0). Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. It is a selective cancer dependency (DepMap: 14.2% of cell lines).

Predicted to enable GTP binding activity; GTPase activity; and protein kinase binding activity. Involved in actin filament organization. Located in extracellular exosome.

Source: NCBI Gene 54509 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 39 total
• GTEx eGene: eQTL in 32 tissues, sQTL in 33 (q < 0.05)
• Cancer dependency (DepMap): dependent in 14.2% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.53 (unconstrained)
• MANE Select transcript: NM_019034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15703
Approved symbol	RHOF
Name	ras homolog family member F, filopodia associated
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20247, RIF
Ensembl gene	ENSG00000139725
Ensembl biotype	protein_coding
OMIM	618867
Entrez	54509

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000267205

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 5: 4

ENST00000267205, ENST00000535560, ENST00000537171, ENST00000537265, ENST00000541657, ENST00000545544, ENST00000546227, ENST00000984996, ENST00001038381, ENST00001067622, ENST00001113634, ENST00001124447, ENST00001127034, ENST00001138479

RefSeq mRNA: 1 — MANE Select: NM_019034 NM_019034

CCDS: CCDS9222

Canonical transcript exons

ENST00000267205 — 5 exons

Exon	Start	End
ENSE00001320034	121777754	121779662
ENSE00003705133	121793152	121793239
ENSE00003708134	121781083	121781192
ENSE00003708483	121780872	121781006
ENSE00003842855	121793496	121793688

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 94.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7424 / max 995.1086, expressed in 1682 samples.

Highest expression (Bgee): granulocyte, lower esophagus mucosa, blood, mucosa of transverse colon, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RHOF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 33 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 65 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	1.5e-33	+0.79	12:121800474:T:G
Nerve Tibial	sqtl	1.8e-24	+0.73	12:121793667:C:T
Testis	sqtl	3.2e-22	+0.86	12:121800474:T:G
Skin Sun Exposed Lower leg	sqtl	1.8e-16	+0.61	12:121810676:C:G
Cells Cultured fibroblasts	eqtl	6.0e-16	-0.39	12:121818562:C:CA
Nerve Tibial	eqtl	1.4e-15	+0.32	12:121801702:A:G
Skin Sun Exposed Lower leg	eqtl	1.5e-14	+0.30	12:121796183:T:A
Pituitary	eqtl	8.8e-13	+0.54	12:121800394:G:A
Adipose Subcutaneous	eqtl	3.9e-12	-0.30	12:121825909:C:G
Artery Tibial	eqtl	5.3e-12	+0.25	12:121807183:A:G
Muscle Skeletal	sqtl	1.2e-11	-0.54	12:121805999:C:T
Lung	sqtl	1.3e-11	+0.51	12:121813750:G:A
Brain Cerebellum	sqtl	2.1e-11	-0.96	12:121796183:T:A
Skin Not Sun Exposed Suprapubic	sqtl	4.2e-11	-0.56	12:121838758:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-10	+0.25	12:121801168:C:A
Breast Mammary Tissue	eqtl	7.3e-10	+0.29	12:121800394:G:A
Esophagus Mucosa	eqtl	1.2e-09	-0.33	12:121783628:G:A
Colon Transverse	sqtl	4.9e-09	+0.52	12:121795589:G:C
Esophagus Mucosa	sqtl	8.7e-09	+0.50	12:121815398:G:GC
Minor Salivary Gland	eqtl	1.1e-08	-0.62	12:121818535:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
133758	22.9672	1312
133759	12.5225	1473
133761	1.3954	659
133763	1.1487	549
133760	0.4756	111
133757	0.1248	52
133752	0.1082	36

Top tissues by expression

showing 100 of 269 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.96	gold quality
lower esophagus mucosa	UBERON:0035834	91.77	gold quality
blood	UBERON:0000178	91.43	gold quality
mucosa of transverse colon	UBERON:0004991	90.84	gold quality
apex of heart	UBERON:0002098	89.62	gold quality
lymph node	UBERON:0000029	89.05	gold quality
cartilage tissue	UBERON:0002418	88.22	gold quality
duodenum	UBERON:0002114	87.83	gold quality
jejunal mucosa	UBERON:0000399	87.25	gold quality
spleen	UBERON:0002106	86.28	gold quality
leukocyte	CL:0000738	86.09	gold quality
epithelium of nasopharynx	UBERON:0001951	85.57	gold quality
bone marrow cell	CL:0002092	85.49	gold quality
vermiform appendix	UBERON:0001154	85.38	gold quality
monocyte	CL:0000576	85.29	gold quality
mononuclear cell	CL:0000842	85.28	gold quality
colonic mucosa	UBERON:0000317	85.28	gold quality
upper lobe of left lung	UBERON:0008952	84.84	gold quality
bone marrow	UBERON:0002371	84.66	gold quality
upper lobe of lung	UBERON:0008948	84.49	gold quality
metanephros cortex	UBERON:0010533	84.44	gold quality
amniotic fluid	UBERON:0000173	84.39	gold quality
ileal mucosa	UBERON:0000331	84.27	silver quality
heart left ventricle	UBERON:0002084	84.22	gold quality
cardiac ventricle	UBERON:0002082	84.03	gold quality
adrenal tissue	UBERON:0018303	83.74	gold quality
caecum	UBERON:0001153	83.35	gold quality
small intestine	UBERON:0002108	83.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.04	gold quality
transverse colon	UBERON:0001157	82.92	gold quality
right lobe of thyroid gland	UBERON:0001119	82.49	gold quality
left lobe of thyroid gland	UBERON:0001120	81.91	gold quality
bone element	UBERON:0001474	81.69	gold quality
ectocervix	UBERON:0012249	81.64	gold quality
pancreatic ductal cell	CL:0002079	81.46	silver quality
right hemisphere of cerebellum	UBERON:0014890	81.23	gold quality
thyroid gland	UBERON:0002046	81.12	gold quality
right lung	UBERON:0002167	81.04	gold quality
cerebellar vermis	UBERON:0004720	80.95	silver quality
left adrenal gland cortex	UBERON:0035825	80.80	gold quality
left adrenal gland	UBERON:0001234	80.68	gold quality
jejunum	UBERON:0002115	80.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.62	gold quality
intestine	UBERON:0000160	80.42	gold quality
rectum	UBERON:0001052	80.33	gold quality
substantia nigra pars compacta	UBERON:0001965	80.31	silver quality
right adrenal gland	UBERON:0001233	80.25	gold quality
buccal mucosa cell	CL:0002336	80.24	gold quality
adrenal gland	UBERON:0002369	80.21	gold quality
cerebellar cortex	UBERON:0002129	80.17	gold quality
body of stomach	UBERON:0001161	80.11	gold quality
cerebellar hemisphere	UBERON:0002245	80.06	gold quality
adrenal cortex	UBERON:0001235	80.00	gold quality
right adrenal gland cortex	UBERON:0035827	79.75	gold quality
lung	UBERON:0002048	79.71	gold quality
cerebellum	UBERON:0002037	79.67	gold quality
heart right ventricle	UBERON:0002080	79.67	gold quality
colon	UBERON:0001155	79.59	gold quality
large intestine	UBERON:0000059	79.58	gold quality
superficial temporal artery	UBERON:0001614	79.48	silver quality
prefrontal cortex	UBERON:0000451	79.28	gold quality
heart	UBERON:0000948	79.08	gold quality
stomach	UBERON:0000945	79.05	gold quality
endocervix	UBERON:0000458	78.99	gold quality
trabecular bone tissue	UBERON:0002483	78.68	gold quality
parotid gland	UBERON:0001831	78.53	silver quality
right frontal lobe	UBERON:0002810	78.04	gold quality
stromal cell of endometrium	CL:0002255	77.30	gold quality
esophagus mucosa	UBERON:0002469	77.11	gold quality
right atrium auricular region	UBERON:0006631	76.89	gold quality
frontal cortex	UBERON:0001870	76.68	gold quality
cortex of kidney	UBERON:0001225	76.67	gold quality
esophagus	UBERON:0001043	76.57	gold quality
tonsil	UBERON:0002372	76.53	gold quality
smooth muscle tissue	UBERON:0001135	76.18	gold quality
neocortex	UBERON:0001950	76.15	gold quality
anterior cingulate cortex	UBERON:0009835	75.98	gold quality
cingulate cortex	UBERON:0003027	75.96	gold quality
lower esophagus	UBERON:0013473	75.93	gold quality
body of uterus	UBERON:0009853	75.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.84	gold quality
right uterine tube	UBERON:0001302	75.83	gold quality
gall bladder	UBERON:0002110	75.79	gold quality
lower lobe of lung	UBERON:0008949	75.66	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	75.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	75.63	silver quality
oral cavity	UBERON:0000167	75.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.51	gold quality
uterine cervix	UBERON:0000002	75.46	gold quality
urinary bladder	UBERON:0001255	75.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.44	gold quality
mucosa of stomach	UBERON:0001199	75.40	gold quality
oviduct epithelium	UBERON:0004804	75.35	gold quality
fallopian tube	UBERON:0003889	75.29	gold quality
fundus of stomach	UBERON:0001160	75.18	gold quality
cardiac atrium	UBERON:0002081	75.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	75.06	silver quality
left uterine tube	UBERON:0001303	75.03	gold quality
vagina	UBERON:0000996	74.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-86618	yes	459.60
E-MTAB-8142	yes	25.44
E-MTAB-7249	yes	10.98
E-ANND-3	yes	4.84
E-CURD-120	no	7.06

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	44.7	low
Frontal cortex	tissue	42.2
Lymph node	tissue	38.3	high
Hippocampal formation	tissue	32.4
Spleen	tissue	31.4	high
Choroid plexus	tissue	30.9
Small intestine	tissue	30.5	low
Cerebral cortex	tissue	30.4	medium
Somatosensory cortex	tissue	30.4
Duodenum	tissue	30.0	not detected
Tonsil	tissue	29.4	high
Prefrontal cortex	tissue	29.2
Occipital cortex	tissue	29.1
Septum	tissue	28.4
Motor cortex	tissue	28.0
Postcentral gyrus	tissue	27.6
Retrosplenial and cingulate cortex	tissue	27.5
Basal ganglia	tissue	27.4	not detected
Temporal cortex	tissue	27.2
Locus coeruleus	tissue	26.7
Thalamus	tissue	26.6
Stomach 1	tissue	26.5	high
Entorhinal cortex	tissue	26.4
Ventral forebrain	tissue	25.6
Appendix	tissue	25.1	medium
Retrosplenial cortex	tissue	25.0
Insular cortex	tissue	24.9
Amygdala	tissue	24.8
Pons	tissue	24.7
Putamen	tissue	24.0
Nucleus accumbens	tissue	24.0
Thymus	tissue	23.8
Caudate putamen	tissue	23.4
Cerebellum	tissue	23.1	not detected
Substantia nigra	tissue	22.9
Colon	tissue	22.8	low
Superior colliculi	tissue	22.6
Hypothalamus	tissue	22.1
Midbrain	tissue	22.0
Hippocampus	tissue	21.8	not detected
Epididymis	tissue	20.5	medium
Periaqueductal gray	tissue	19.7
Medulla oblongata	tissue	19.4
Lung	tissue	19.4	medium
Rectum	tissue	18.1	low
Spinal cord	tissue	15.6
Olfactory bulb	tissue	14.5
Thyroid gland	tissue	13.7	not detected
Corpus callosum	tissue	13.1
Endometrium 1	tissue	12.3	low
Heart muscle	tissue	11.1	not detected
Skeletal muscle	tissue	11.1	not detected
Salivary gland	tissue	10.8	low
Smooth muscle	tissue	10.8	not detected
Fallopian tube	tissue	9.4	not detected
Esophagus	tissue	9.3	not detected
Retina	tissue	9.2
Seminal vesicle	tissue	9.2	not detected
Gallbladder	tissue	9.2	not detected
Adrenal gland	tissue	9.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Flocculonodular lobe (53.0), Vermis (51.3), Cerebellar cortex (50.2), Nuclei of the trapezoid body (36.2), Pontine nuclei (36.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting RHOF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 93 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325

Functional genomics

gnomAD constraint: pLI 7.39e-10, LOEUF 1.53, missense Z -0.244 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000267205 — one region, missense o/e 0.97. DepMap (CRISPR cell-line fitness): dependent in 14.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H1573 (-1.224), NB-4 (-1.065), BT-16 (-1.017), T84 (-0.989), Yamato (-0.98), SMZ-1 (-0.909), SNU-977 (-0.878), NGP (-0.872), JVE-187 (-0.86), SNU-620 (-0.857), C-4 I (-0.855), OAW42 (-0.854), OS526 (-0.848), S-117 (-0.839), SUM-185PE (-0.829).

Literature-anchored findings (GeneRIF, showing 6)

• The protein encoded by this gene causes the formation of long, actin-rich filopodia. In combination with RAC1 and CDC42 it causes additional actin rearrangments, suggesting that this protein is intimately involved in regulation of the cytoskeleton. (PMID:11084341)
• deletion of genes RHOF in early-stage mycosis fungoides. (PMID:18663754)
• Rif GTPase is an alternative trigger of stress-fiber formation in epithelial cells. (PMID:20233848)
• The authors show that enteropathogenic Escherichia coli translocates EspH, which inactivates mammalian RhoGEFs and triggers cytotoxicity. (PMID:22251971)
• In the present review, our aim is to summarize the current information about the Rif effectors and how Rif remodels actin cytoskeleton in many aspects. [Review] (PMID:22260703)
• Rif has two separate roles in FARP1 regulation-in controlling its association with plexinA4, and in releasing active RhoA from a plexinA4/FARP1 complex. (PMID:25668492)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhof	ENSDARG00000054389
mus_musculus	Rhof	ENSMUSG00000029449
rattus_norvegicus	Rhof	ENSRNOG00000042607

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RND3 (ENSG00000115963), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RHOT1 (ENSG00000126858), RAC2 (ENSG00000128340), RAC1 (ENSG00000136238), RHOT2 (ENSG00000140983), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1345629) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal spleen marginal zone morphology	1
thrombocytopenia	1
decreased marginal zone B cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P61585	100.0%	Diamond
Pongo abelii	Q5RCK9	100.0%	Diamond
Sus scrofa	O77683	99.6%	Diamond
Canis lupus familiaris	P24406	99.5%	Diamond
Gallus gallus	Q9PSX7	96.9%	Diamond
Cavia porcellus	P80236	96.3%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q8J212	91.3%	Diamond
Eremothecium gossypii ATCC 10895	Q9HF54	91.3%	Diamond
Aplysia californica	P01122	89.6%	Diamond
Drosophila melanogaster	P48148	89.6%	Diamond
Diplobatis ommata	P22122	88.6%	Diamond
Caenorhabditis elegans	Q22038	88.1%	Diamond
Schizosaccharomyces pombe 972h-	Q09914	86.1%	Diamond
Aspergillus nidulans FGSC A4	Q9C3Y4	85.7%	Diamond
Saccharomyces cerevisiae S288C	P06780	83.3%	Diamond
Candida albicans SC5314	O42825	79.8%	Diamond
Dictyostelium discoideum	Q54FK8	65.2%	Diamond
Schizophyllum commune	Q9P8J9	56.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMEM120B	protein-coding	144404
SETD1B	protein-coding	23067
MORN3	protein-coding	283385
LINC01089	ncRNA	338799
ORAI1	protein-coding	84876
CFAP251	protein-coding	144406
HPD	protein-coding	3242
PSMD9	protein-coding	5715
TIALD	ncRNA	105370035
KDM2B-DT	ncRNA	101928346
KDM2B	protein-coding	84678

Protein

Protein identifiers

Rho-related GTP-binding protein RhoF — Q9HBH0 (reviewed: Q9HBH0)

Alternative names: Rho family GTPase Rif, Rho in filopodia

All UniProt accessions (5): Q9HBH0, F5GXB1, V9GY67, V9GYB3, V9GYQ1

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Causes the formation of thin, actin-rich surface projections called filopodia. Functions cooperatively with CDC42 and Rac to generate additional structures, increasing the diversity of actin-based morphology.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the small GTPase superfamily. Rho family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HBH0-1	1	yes
Q9HBH0-2	2

RefSeq proteins (1): NP_061907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR003578	Small_GTPase_Rho	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

Catalyzed reactions (Rhea)

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (25 total): binding site 15, modified residue 2, splice variant 2, sequence conflict 2, chain 1, propeptide 1, short sequence motif 1, lipid moiety-binding region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBH0-F1	92.25	0.83

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (15)

Position	Role
51	GTP
51	Mg(2+)
73	Mg(2+)
76	GTP
132	GTP
134	GTP
175	GTP
176	GTP
29	GTP
30	GTP
31	GTP
32	GTP
33	GTP
33	Mg(2+)
48	GTP

Post-translational modifications (3)

Type	Positions
N-acetylmethionine	1
Cysteine methyl ester	208
S-geranylgeranyl cysteine	208

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-9035034	RHOF GTPase cycle	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 232 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, RODRIGUES_NTN1_TARGETS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, AMIT_EGF_RESPONSE_480_MCF10A, RICKMAN_METASTASIS_DN, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, WOO_LIVER_CANCER_RECURRENCE_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOCC_SECRETORY_VESICLE, AACATTC_MIR4093P

GO Biological Process (6): actin filament organization (GO:0007015), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), cell migration (GO:0016477), regulation of actin cytoskeleton organization (GO:0032956), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (5): GTPase activity (GO:0003924), guanyl-nucleotide exchange factor activity (GO:0005085), GTP binding (GO:0005525), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166)

GO Cellular Component (5): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Innate Immune System	1
RHO GTPase cycle	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

32 GO namespaces:

Category	Terms
actin cytoskeleton organization	2
supramolecular fiber organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
cell motility	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
ribonucleoside triphosphate phosphatase activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoplasm	1
cellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
actin filament organization	BP	direct assay
extracellular exosome	CC	high-throughput assay

Protein interactions and networks

STRING

showing 16 of 960 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOF	TMEM120B	A0PK00	569
RHOF	DIAPH3	Q9NSV4	464
RHOF	SOWAHA	Q2M3V2	452
RHOF	GTPBP4	Q9BZE4	440
RHOF	RHOBTB3	O94955	423
RHOF	DOCK10	Q96BY6	411
RHOF	NIBAN2	Q96TA1	408
RHOF	CDC42SE2	Q9NRR3	401
RHOF	RHOH	Q15669	383
RHOF	DOCK5	Q9H7D0	375
RHOF	ARRDC2	Q8TBH0	370
RHOF	RASL11B	Q9BPW5	370
RHOF	SYDE2	Q5VT97	370
RHOF	CNKSR1	Q969H4	370
RHOF	TMEM120A	Q9BXJ8	370
RHOF	RASSF1	Q9NS23	370

IntAct

Human interaction partners of RHOF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
DIAPH1	direct interaction	0.440	1
GSTT1	association	0.350	1
STIP1	association	0.350	1

BioGRID (687 interactions; top human partners by supporting records in a sample of 600 records): RAP1GDS1 (Affinity Capture-MS; 3 records), ANKFY1 (Affinity Capture-Western; 2 records), CCT6B (Affinity Capture-MS; 2 records), KIF14 (Affinity Capture-MS; 2 records), NAA25 (Affinity Capture-MS; 2 records), AAAS (Affinity Capture-MS), ABCB7 (Affinity Capture-MS), ABCC1 (Affinity Capture-MS), ABCC5 (Affinity Capture-MS), ABCE1 (Affinity Capture-MS), ABI2 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ACSL3 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ACTB (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for RHOF: 39 ClinVar records (0 pathogenic / likely pathogenic); 15 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 237):

Position(s)	Effect	Δscore	Sites
12:121779663	acceptor_gain	1.0000
12:121779663–121779664	acceptor_loss	1.0000	3
12:121779667	acceptor_gain	1.0000
12:121780870–121780871	donor_loss	1.0000	2
12:121780874	donor_gain	1.0000
12:121780976	acceptor_gain	1.0000
12:121781007–121781008	acceptor_loss	1.0000	6
12:121781081–121781082	donor_loss	1.0000	5
12:121781193	acceptor_gain	1.0000
12:121781193–121781194	acceptor_loss	1.0000	5

AlphaMissense

662 missense substitutions predicted likely pathogenic (of 1,363 scored), across 153 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D73	8	0.997	0.999
D134	8	0.989	0.996
D27	8	0.988	0.996
F53	8	0.973	0.998
F185	8	0.962	0.994
F44	8	0.957	0.998
D99	8	0.954	0.995
D81	8	0.952	0.980
D79	8	0.935	0.984
H119	8	0.862	0.971
W113	7	0.993	0.999
K32	7	0.987	0.998
E116	7	0.984	0.992
F120	7	0.979	0.998
E172	7	0.972	0.990
R136	7	0.964	0.997
S105	7	0.952	0.999
K132	7	0.937	0.998
C30	7	0.934	0.996
C173	7	0.926	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	5.18e-06
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	8.32e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000254
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000437
Glioblastoma Multiforme (validation)	favorable	0.000654
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000902

Disease associations

OMIM: gene MIM:618867 | disease phenotypes:

GWAS associations

15 associations:

Study	Trait	p-value
GCST004599_145	Mean platelet volume	0.000000e+00
GCST90002395_560	Mean platelet volume	0.000000e+00
GCST90002401_551	Platelet distribution width	2e-212
GCST90002400_630	Plateletcrit	9e-196
GCST004616_105	Platelet distribution width	1e-184
GCST90002402_226	Platelet count	4e-127
GCST004607_60	Plateletcrit	6e-81
GCST004603_53	Platelet count	1e-45
GCST90002406_558	Reticulocyte fraction of red cells	3e-22
GCST90002405_336	Reticulocyte count	7e-17
GCST90002386_74	High light scatter reticulocyte percentage of red cells	4e-13
GCST008167_4	Mean platelet volume	8e-11
GCST90002387_394	Immature fraction of reticulocytes	8e-11
GCST90002385_432	High light scatter reticulocyte count	3e-10
GCST004619_213	Reticulocyte fraction of red cells	3e-9

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
entinostat	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, decreases expression	2
Smoke	decreases expression, increases abundance	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ochratoxin A	affects binding	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
beta-hydroxy simvastatin acid	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Troglitazone	increases expression	1
Adenosine Triphosphate	increases expression, decreases reaction	1
Benzene	increases expression	1
Copper	affects binding, increases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.