RASA4B

gene

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Summary

RASA4B (RAS p21 protein activator 4B, HGNC:35202) is a protein-coding gene on chromosome 7q22.1, encoding Ras GTPase-activating protein 4B (C9J798). Ca(2+)-dependent Ras GTPase-activating protein, that may play a role in the Ras-MAPK pathway.

Predicted to enable GTPase activator activity; phospholipid binding activity; and zinc ion binding activity. Predicted to be involved in cellular response to calcium ion; intracellular signal transduction; and negative regulation of Ras protein signal transduction. Predicted to be located in cytosol and plasma membrane.

Source: NCBI Gene 100271927 — RefSeq curated summary.

At a glance

Clinical variants (ClinVar): 4 total
MANE Select transcript: NM_001367767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35202
Approved symbol	RASA4B
Name	RAS p21 protein activator 4B
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170667
Ensembl biotype	protein_coding
Entrez	100271927

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000306682, ENST00000465829, ENST00000467351, ENST00000477184, ENST00000488284, ENST00000495352, ENST00000541662, ENST00000707123, ENST00000879066, ENST00000952237

RefSeq mRNA: 2 — MANE Select: NM_001367767 NM_001277335, NM_001367767

CCDS: CCDS59506, CCDS94160

Canonical transcript exons

ENST00000465829 — 21 exons

Exon	Start	End
ENSE00002275632	102517646	102517777
ENSE00003467023	102510179	102510292
ENSE00003544444	102511925	102511981
ENSE00003703874	102506695	102506824
ENSE00003704976	102500699	102500793
ENSE00003707246	102494538	102494675
ENSE00003707430	102493825	102493969
ENSE00003707758	102490986	102491123
ENSE00003708219	102493116	102493285
ENSE00003708340	102496140	102496204
ENSE00003708457	102495278	102495390
ENSE00003709858	102509599	102509660
ENSE00003710080	102496469	102496619
ENSE00003710090	102496847	102496964
ENSE00003710614	102503163	102503244
ENSE00003710682	102501096	102501227
ENSE00003710870	102494881	102495073
ENSE00003998262	102479976	102483713
ENSE00003998263	102488463	102488598
ENSE00003998265	102485039	102485159
ENSE00003998266	102483825	102483889

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.27.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.27	gold quality
gastrocnemius	UBERON:0001388	96.14	gold quality
muscle of leg	UBERON:0001383	95.26	gold quality
skeletal muscle tissue	UBERON:0001134	95.07	gold quality
muscle tissue	UBERON:0002385	91.00	gold quality
pituitary gland	UBERON:0000007	89.96	gold quality
right coronary artery	UBERON:0001625	89.85	gold quality
endocervix	UBERON:0000458	89.60	gold quality
mucosa of stomach	UBERON:0001199	89.36	gold quality
fundus of stomach	UBERON:0001160	89.02	gold quality
body of uterus	UBERON:0009853	89.01	gold quality
adenohypophysis	UBERON:0002196	88.86	gold quality
ectocervix	UBERON:0012249	88.58	gold quality
myometrium	UBERON:0001296	88.39	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.38	gold quality
right adrenal gland cortex	UBERON:0035827	87.85	gold quality
right ovary	UBERON:0002118	87.73	gold quality
ganglionic eminence	UBERON:0004023	87.51	gold quality
tibial nerve	UBERON:0001323	87.45	gold quality
skin of leg	UBERON:0001511	87.09	gold quality
amygdala	UBERON:0001876	87.03	gold quality
temporal lobe	UBERON:0001871	86.96	gold quality
lower esophagus	UBERON:0013473	86.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.91	gold quality
stromal cell of endometrium	CL:0002255	86.85	gold quality
adipose tissue	UBERON:0001013	86.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.77	gold quality
uterine cervix	UBERON:0000002	86.70	gold quality
mucosa of transverse colon	UBERON:0004991	86.70	gold quality
vagina	UBERON:0000996	86.50	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	19.28
E-GEOD-125970	yes	4.93
E-ANND-3	no	1.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting RASA4B, 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-6721-5P	99.93	68.92	2981
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4308	97.56	67.13	1385

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rasa4	ENSDARG00000029372
mus_musculus	Rasa4	ENSMUSG00000004952
rattus_norvegicus	Rasa4	ENSRNOG00000001431
drosophila_melanogaster	RasGAP1	FBGN0004390
drosophila_melanogaster	raskol	FBGN0261570
caenorhabditis_elegans		WBGENE00001515
caenorhabditis_elegans		WBGENE00001516

Paralogs (10): RASAL2 (ENSG00000075391), RASAL3 (ENSG00000105122), RASA4 (ENSG00000105808), RASAL1 (ENSG00000111344), DAB2IP (ENSG00000136848), RASA1 (ENSG00000145715), RASA2 (ENSG00000155903), RASA3 (ENSG00000185989), NF1 (ENSG00000196712), SYNGAP1 (ENSG00000197283)

Protein

Protein identifiers

Ras GTPase-activating protein 4B — C9J798 (reviewed: C9J798)

All UniProt accessions (4): C9J798, A0A9L9PXW0, F5GXT2, F8W6L0

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+)-dependent Ras GTPase-activating protein, that may play a role in the Ras-MAPK pathway.

Subcellular location. Cytoplasm. Cytosol. Cell membrane.

Cofactor. Binds 3 Ca(2+) ions per C2 domain.

RefSeq proteins (2): NP_001264264, NP_001354696* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001562	Znf_Btk_motif	Conserved_site
IPR001849	PH_domain	Domain
IPR001936	RasGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR023152	RasGAP_CS	Conserved_site
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037777	RASA4_PH	Domain
IPR039360	Ras_GTPase	Family

Pfam: PF00168, PF00169, PF00616, PF00779

UniProt features (34 total): binding site 26, domain 4, chain 1, site 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9J798-F1	86.74	0.59

Functional residue map

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

Catalytic / active sites (1): 343 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Ligand- & substrate-binding residues (26): 74; 74; 76; 76; 76; 79; 82; 82; 149; 149; 155; 202 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): GOLDRATH_IMMUNE_MEMORY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_RESPONSE_TO_METAL_ION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, TSENG_IRS1_TARGETS_DN, MORI_PRE_BI_LYMPHOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, BURTON_ADIPOGENESIS_9, GOBP_RESPONSE_TO_CALCIUM_ION, GOMF_ENZYME_ACTIVATOR_ACTIVITY

GO Biological Process (5): intracellular signal transduction (GO:0035556), negative regulation of Ras protein signal transduction (GO:0046580), cellular response to calcium ion (GO:0071277), regulation of intracellular signal transduction (GO:1902531), regulation of GTPase activity (GO:0043087)

GO Molecular Function (4): GTPase activator activity (GO:0005096), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
GTPase activity	2
signal transduction	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
response to calcium ion	1
cellular response to metal ion	1
regulation of signal transduction	1
intracellular signal transduction	1
regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
lipid binding	1
transition metal ion binding	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PCNA	RASA4B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): RASA4B (Affinity Capture-MS), RASA4B (Affinity Capture-MS), RASA4B (Affinity Capture-MS), RASA4B (Affinity Capture-MS), RASA4B (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: A0AVI2, A0JJX5, A3KGK3, B2RUP2, C9J798, O43374, O95294, P48231, Q2WGJ9, Q54E35, Q5SPC5, Q8L706, Q8L7A4, Q8W4D4, Q9ERC5, Q9ESF1, Q9FVJ3, Q9HC10, Q9R189, Q9UT00, A0A075F932, A0FGR9, K8FE10, O00445, O35681, O43581, O94812, P04409, P05128, P10829, P13677, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3278 predictions. Top by Δscore:

Variant	Effect	Δscore
7:102483714:C:CC	acceptor_gain	1.0000
7:102483888:CC:C	acceptor_gain	1.0000
7:102483889:CC:C	acceptor_gain	1.0000
7:102485032:GACTC:G	donor_loss	1.0000
7:102485033:ACTCA:A	donor_loss	1.0000
7:102485034:CTCAC:C	donor_loss	1.0000
7:102485035:TCACC:T	donor_loss	1.0000
7:102485036:CAC:C	donor_loss	1.0000
7:102485037:A:AC	donor_gain	1.0000
7:102485037:A:T	donor_loss	1.0000
7:102485037:AC:A	donor_gain	1.0000
7:102485038:C:CA	donor_loss	1.0000
7:102485038:C:CC	donor_gain	1.0000
7:102485038:CC:C	donor_gain	1.0000
7:102485038:CCA:C	donor_gain	1.0000
7:102485155:CTGAC:C	acceptor_gain	1.0000
7:102485156:TGAC:T	acceptor_gain	1.0000
7:102485157:GAC:G	acceptor_gain	1.0000
7:102485158:AC:A	acceptor_gain	1.0000
7:102485159:CC:C	acceptor_gain	1.0000
7:102485160:C:CC	acceptor_gain	1.0000
7:102485160:CTGG:C	acceptor_loss	1.0000
7:102485167:C:CT	acceptor_gain	1.0000
7:102488599:C:CC	acceptor_gain	1.0000
7:102493111:CCCA:C	donor_gain	1.0000
7:102493114:A:C	donor_loss	1.0000
7:102493284:CT:C	acceptor_gain	1.0000
7:102493286:C:CC	acceptor_gain	1.0000
7:102493290:C:CT	acceptor_gain	1.0000
7:102493295:C:CT	acceptor_gain	1.0000

AlphaMissense

5223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:102510258:A:G	W53R	0.999
7:102510258:A:T	W53R	0.999
7:102488493:A:G	W692R	0.998
7:102488493:A:T	W692R	0.998
7:102488577:A:G	W664R	0.998
7:102488577:A:T	W664R	0.998
7:102510256:C:A	W53C	0.998
7:102510256:C:G	W53C	0.998
7:102517671:C:A	G14W	0.998
7:102501200:A:G	W180R	0.997
7:102501200:A:T	W180R	0.997
7:102511959:A:G	C30R	0.997
7:102517671:C:G	G14R	0.997
7:102517671:C:T	G14R	0.997
7:102488491:C:A	W692C	0.996
7:102488491:C:G	W692C	0.996
7:102494620:G:T	A478D	0.996
7:102501198:C:A	W180C	0.996
7:102501198:C:G	W180C	0.996
7:102509643:C:T	G85E	0.996
7:102510263:G:T	P51H	0.996
7:102511957:G:C	C30W	0.996
7:102517670:C:T	G14E	0.996
7:102488520:G:C	H683D	0.995
7:102494598:G:C	F485L	0.995
7:102494598:G:T	F485L	0.995
7:102494600:A:G	F485L	0.995
7:102503200:A:T	V158D	0.995
7:102510200:A:T	V72D	0.995
7:102510257:C:G	W53S	0.995

dbSNP variants (sampled 300 via entrez): RS1001461059 (7:102482212 C>G), RS1001492099 (7:102507216 G>A,T), RS1008378953 (7:102514776 AG>A), RS1009035682 (7:102508876 G>A,T), RS1009129184 (7:102486647 G>T), RS1009222167 (7:102480063 G>A,C), RS1010511456 (7:102511472 C>G), RS1010898674 (7:102487213 C>T), RS1014215422 (7:102480250 A>T), RS1014329662 (7:102480505 T>G), RS1019037384 (7:102508888 G>T), RS1019176035 (7:102486656 C>T), RS1020490724 (7:102487300 A>C), RS1020943352 (7:102511563 G>C), RS10227603 (7:102498268 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
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
abrine	decreases expression	1
asparanin A	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, decreases methylation	1
Glyphosate	increases expression	1
Doxorubicin	decreases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.