RABIF

Summary

RABIF (RAB interacting factor, HGNC:9797) is a protein-coding gene on chromosome 1q32.1, encoding Guanine nucleotide exchange factor MSS4 (P47224). Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. It is a selective cancer dependency (DepMap: 26.7% of cell lines).

This gene encodes a member of the SCE4/YPT1/RAB family of small GTP-binding proteins that are involved in the regulation of intracellular vesicular transport. This protein stimulates GTP-GDP exchange in SEC4, and to a lesser extent in YPT1 and RAB3A, and may play a general role in vesicular transport.

Source: NCBI Gene 5877 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 13 total
• Cancer dependency (DepMap): dependent in 26.7% of screened cell lines
• MANE Select transcript: NM_002871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9797
Approved symbol	RABIF
Name	RAB interacting factor
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	mss4
Ensembl gene	ENSG00000183155
Ensembl biotype	protein_coding
OMIM	603417
Entrez	5877

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367262, ENST00000914087

RefSeq mRNA: 1 — MANE Select: NM_002871 NM_002871

CCDS: CCDS1428

Canonical transcript exons

ENST00000367262 — 2 exons

Exon	Start	End
ENSE00001444003	202878282	202881223
ENSE00001444005	202888973	202889149

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 94.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5975 / max 150.7908, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16743	25.5019	1813
16744	0.9944	595
16745	0.3961	185
16746	0.3563	159
16742	0.2809	134
16747	0.0680	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	94.75	gold quality
sperm	CL:0000019	93.20	gold quality
tongue squamous epithelium	UBERON:0006919	92.12	gold quality
male germ cell	CL:0000015	91.74	silver quality
squamous epithelium	UBERON:0006914	88.43	gold quality
hair follicle	UBERON:0002073	88.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.31	gold quality
cervix epithelium	UBERON:0004801	88.09	silver quality
gingival epithelium	UBERON:0001949	87.61	gold quality
epithelium of esophagus	UBERON:0001976	86.90	gold quality
endothelial cell	CL:0000115	86.71	gold quality
gingiva	UBERON:0001828	86.58	gold quality
amniotic fluid	UBERON:0000173	86.38	gold quality
esophagus squamous epithelium	UBERON:0006920	86.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.04	gold quality
epithelial cell of pancreas	CL:0000083	85.70	silver quality
pancreatic ductal cell	CL:0002079	85.62	gold quality
adult organism	UBERON:0007023	84.62	gold quality
palpebral conjunctiva	UBERON:0001812	84.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.30	gold quality
left testis	UBERON:0004533	84.23	gold quality
right testis	UBERON:0004534	84.22	gold quality
secondary oocyte	CL:0000655	84.13	gold quality
endometrium epithelium	UBERON:0004811	83.98	gold quality
testis	UBERON:0000473	83.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.57	gold quality
epithelium of nasopharynx	UBERON:0001951	83.21	gold quality
nasal cavity epithelium	UBERON:0005384	83.18	gold quality
bone marrow	UBERON:0002371	82.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

97 targeting RABIF, 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-3163	100.00	77.23	8605
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-4283	100.00	66.42	2097
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4261	99.59	70.30	3415

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• MSS4 modulates Rab15 activity in early endocytosis (PMID:12105226)
• The expression levels of cellular Mss4 mRNA and protein are rapidly changed in response to a broad range of extracellular stress stimuli. (PMID:22495352)
• The findings reveal a crucial role of RABIF in vesicle transport and establish RABIF as a Rab-stabilizing holdase chaperone, a previously unrecognized mode of Rab regulation independent of its GDP-releasing activity. (PMID:28894007)
• Identification of the Roles of Coagulation-related Signature and its Key Factor RABIF in Hepatoma Cell Malignancy. (PMID:37644748)
• RABIF promotes hepatocellular carcinoma progression through regulation of mitophagy and glycolysis. (PMID:39414994)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rabif	ENSDARG00000002690
mus_musculus	Rabif	ENSMUSG00000042229
rattus_norvegicus	Rabif	ENSRNOG00000004424
rattus_norvegicus	LOC120100841	ENSRNOG00000063309
drosophila_melanogaster	strat	FBGN0032020
caenorhabditis_elegans		WBGENE00014938

Protein

Protein identifiers

Guanine nucleotide exchange factor MSS4 — P47224 (reviewed: P47224)

Alternative names: Rab-interacting factor

All UniProt accessions (1): P47224

UniProt curated annotations — full annotation on UniProt →

Function. Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1, RAB3A and RAB10, but is less active on these proteins than on the SEC4 protein. Might play a general role in vesicular transport.

Subunit / interactions. Interacts with RAB8A.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the DSS4/MSS4 family.

RefSeq proteins (1): NP_002862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007515	Mss4	Family
IPR011057	Mss4-like_sf	Homologous_superfamily
IPR011323	Mss4/transl-control_tumour	Homologous_superfamily

Pfam: PF04421

UniProt features (23 total): strand 11, binding site 4, helix 2, turn 2, chain 1, domain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2FU5	X-RAY DIFFRACTION	2
1FWQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47224-F1	89.85	0.78

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 (4): 23; 26; 94; 97

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, FISCHER_G1_S_CELL_CYCLE, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_195, MODULE_301, ATTCTTT_MIR186, SCHLOSSER_SERUM_RESPONSE_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, STONER_ESOPHAGEAL_CARCINOGENESIS_DN

GO Biological Process (4): post-Golgi vesicle-mediated transport (GO:0006892), small GTPase-mediated signal transduction (GO:0007264), protein transport (GO:0015031), membrane fusion (GO:0061025)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
Golgi vesicle transport	1
intracellular signaling cassette	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
membrane organization	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

4302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RABIF	GRB2	P29354	995
RABIF	SOS1	Q07889	981
RABIF	LCP2	Q13094	978
RABIF	CDC42	P21181	971
RABIF	SOS2	Q07890	965
RABIF	ARF1	P10947	953
RABIF	RHOA	P06749	945
RABIF	MCF2	P10911	935
RABIF	TIAM1	Q13009	933
RABIF	RASA1	P20936	930
RABIF	RAB8A	P24407	927
RABIF	RCC1	P18754	927
RABIF	AKT1	P31749	924
RABIF	NCK1	P16333	917
RABIF	CYTH1	Q15438	913

IntAct

104 interactions, top by confidence:

A	B	Type	Score
RABIF	RAB8A	psi-mi:“MI:0915”(physical association)	0.850
RAB8A	RABIF	psi-mi:“MI:0407”(direct interaction)	0.850
RABIF	RAB1B	psi-mi:“MI:0915”(physical association)	0.800
RABIF	RAB3A	psi-mi:“MI:0915”(physical association)	0.780
RAB3A	RABIF	psi-mi:“MI:0915”(physical association)	0.780
RABIF	RAB3A	psi-mi:“MI:0914”(association)	0.780
RABIF	RAB1A	psi-mi:“MI:0915”(physical association)	0.670
RAB1A	RABIF	psi-mi:“MI:0915”(physical association)	0.670
RAB3B	RABIF	psi-mi:“MI:0915”(physical association)	0.670
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
TCF4	RABIF	psi-mi:“MI:0915”(physical association)	0.560
REL	RABIF	psi-mi:“MI:0915”(physical association)	0.560
RASSF5	RABIF	psi-mi:“MI:0915”(physical association)	0.560
RABIF	TCF4	psi-mi:“MI:0915”(physical association)	0.560
RABIF	RASSF5	psi-mi:“MI:0915”(physical association)	0.560
RABIF	LNX1	psi-mi:“MI:0915”(physical association)	0.560
RABIF	LZTS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (98): RABIF (Two-hybrid), REL (Two-hybrid), TCF4 (Two-hybrid), RASSF5 (Two-hybrid), AHSA1 (Co-fractionation), KIAA0368 (Co-fractionation), NARS (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation), RABIF (Co-fractionation)

ESM2 similar proteins: A1KXW8, A6QL50, E1BGQ2, H0Y354, O94955, P47224, Q08326, Q0IIH8, Q1JQA1, Q1RMS8, Q1RMZ1, Q2TBU5, Q3T1H6, Q4R372, Q4R528, Q4R9C4, Q5F480, Q5F4A1, Q5I0G3, Q5RCQ0, Q5RFG8, Q5TFE4, Q5TYM5, Q641X7, Q6L9T8, Q6PIP5, Q7L622, Q7Z6J8, Q7ZX59, Q86X60, Q8BFZ8, Q8BKW4, Q8BM85, Q8BX13, Q8CEL2, Q8N5C7, Q8N635, Q8NHU2, Q8TCF1, Q8TCJ0

Diamond homologs: O43057, P47224, Q08326, Q91X96, Q9VLP3, Q9U1X4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
RAB geranylgeranylation	12	48.3×	2e-15
RAB GEFs exchange GTP for GDP on RABs	8	23.1×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
exocytosis	9	26.8×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

392 predictions. Top by Δscore:

Variant	Effect	Δscore
1:202888969:CTA:C	donor_loss	1.0000
1:202888970:TACC:T	donor_loss	1.0000
1:202888971:ACC:A	donor_loss	1.0000
1:202888972:C:A	donor_loss	1.0000
1:202880980:A:AC	donor_gain	0.9900
1:202880981:C:CC	donor_gain	0.9900
1:202881219:AAAAG:A	acceptor_gain	0.9900
1:202881220:AAAG:A	acceptor_gain	0.9900
1:202881221:AAG:A	acceptor_gain	0.9900
1:202881222:AG:A	acceptor_gain	0.9900
1:202881223:GC:G	acceptor_loss	0.9900
1:202881224:C:CC	acceptor_gain	0.9900
1:202881225:T:C	acceptor_loss	0.9900
1:202888968:CCTA:C	donor_loss	0.9900
1:202880985:T:C	donor_gain	0.9800
1:202881229:G:C	acceptor_gain	0.9800
1:202888328:T:TA	donor_gain	0.9800
1:202888963:G:A	donor_gain	0.9800
1:202889044:T:TA	donor_gain	0.9800
1:202881228:A:T	acceptor_gain	0.9700
1:202881229:G:GC	acceptor_gain	0.9700
1:202888997:C:A	donor_gain	0.9700
1:202889071:A:AC	donor_gain	0.9700
1:202889072:C:CC	donor_gain	0.9700
1:202880984:A:AC	donor_gain	0.9600
1:202881227:C:CT	acceptor_gain	0.9600
1:202888855:AAGG:A	donor_gain	0.9600
1:202888972:CCTGT:C	donor_gain	0.9600
1:202889004:TGCAG:T	donor_gain	0.9600
1:202889072:CTCG:C	donor_gain	0.9600

AlphaMissense

804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:202881042:C:T	G103D	1.000
1:202881043:C:G	G103R	1.000
1:202881048:G:T	P101Q	1.000
1:202881069:C:T	C94Y	1.000
1:202881070:A:G	C94R	1.000
1:202881075:A:T	L92Q	1.000
1:202881104:G:C	F82L	1.000
1:202881104:G:T	F82L	1.000
1:202881106:A:G	F82L	1.000
1:202881145:A:G	W69R	1.000
1:202881145:A:T	W69R	1.000
1:202881006:A:T	V115E	0.999
1:202881042:C:A	G103V	0.999
1:202881045:A:T	I102N	0.999
1:202881049:G:A	P101S	0.999
1:202881051:C:T	G100E	0.999
1:202881052:C:G	G100R	0.999
1:202881052:C:T	G100R	0.999
1:202881059:A:C	C97W	0.999
1:202881060:C:A	C97F	0.999
1:202881060:C:G	C97S	0.999
1:202881060:C:T	C97Y	0.999
1:202881061:A:G	C97R	0.999
1:202881061:A:T	C97S	0.999
1:202881066:G:T	A95E	0.999
1:202881068:G:C	C94W	0.999
1:202881069:C:A	C94F	0.999
1:202881069:C:G	C94S	0.999
1:202881070:A:T	C94S	0.999
1:202881075:A:G	L92P	0.999

dbSNP variants (sampled 300 via entrez): RS1000252518 (1:202889157 C>A,T), RS1000437732 (1:202883760 T>C), RS1000615324 (1:202880930 G>A,C), RS1001017950 (1:202888116 C>A), RS1001277277 (1:202877779 ATTC>A), RS1002574776 (1:202887656 C>A), RS1002708466 (1:202881729 G>A,T), RS1002711203 (1:202889719 A>C), RS1002791378 (1:202887825 A>G), RS1002927478 (1:202887488 G>A), RS1003184366 (1:202888036 T>C), RS1003753024 (1:202880087 A>T), RS1003808019 (1:202886573 A>T), RS1003887625 (1:202879448 T>C), RS1003902990 (1:202886270 G>A,C,T)

Disease associations

OMIM: gene MIM:603417 | 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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
methylmercuric chloride	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	decreases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Valproic Acid	decreases expression	1
Vincristine	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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