DIRAS1

Summary

DIRAS1 (DIRAS family GTPase 1, HGNC:19127) is a protein-coding gene on chromosome 19p13.3, encoding GTP-binding protein Di-Ras1 (O95057). Displays low GTPase activity and exists predominantly in the GTP-bound form.

DIRAS1 belongs to a distinct branch of the functionally diverse Ras (see HRAS; MIM 190020) superfamily of monomeric GTPases.

Source: NCBI Gene 148252 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 20 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.35 (intermediate), LOEUF 0.91 (unconstrained)
• MANE Select transcript: NM_145173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19127
Approved symbol	DIRAS1
Name	DIRAS family GTPase 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Di-Ras1, GBTS1, RIG
Ensembl gene	ENSG00000176490
Ensembl biotype	protein_coding
OMIM	607862
Entrez	148252

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

MANE Select: ENST00000323469

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

ENST00000323469, ENST00000585334, ENST00000588128, ENST00000861580, ENST00000861581, ENST00000861582, ENST00000861583, ENST00000861584, ENST00000861585, ENST00000861586, ENST00000861587, ENST00000914891, ENST00000914892, ENST00000914893, ENST00001135968

RefSeq mRNA: 1 — MANE Select: NM_145173 NM_145173

CCDS: CCDS12092

Canonical transcript exons

ENST00000323469 — 2 exons

Exon	Start	End
ENSE00001245147	2714567	2717875
ENSE00001309728	2721304	2721372

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2230 / max 195.2116, expressed in 1019 samples.

Highest expression (Bgee): ventricle myocardium, apex of heart, frontal lobe, cortical plate, heart left ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DIRAS1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	2.3e-49	+1.21	19:2726656:C:T
Whole Blood	eqtl	1.5e-24	+0.40	19:2710964:G:A
Cells Cultured fibroblasts	eqtl	1.5e-22	+0.37	19:2721993:A:C
Spleen	eqtl	1.8e-13	+0.56	19:2715743:G:C
Esophagus Gastroesophageal Junction	eqtl	2.6e-09	-0.26	19:2721743:C:T
Artery Aorta	eqtl	3.2e-09	-0.47	19:2721743:C:T
Heart Atrial Appendage	eqtl	5.3e-09	-0.18	19:2719885:T:C
Heart Left Ventricle	eqtl	5.8e-09	-0.19	19:2719885:T:C
Stomach	eqtl	3.8e-08	-0.33	19:2721594:A:G
Nerve Tibial	eqtl	1.9e-04	-0.27	19:2647717:G:C
Brain Nucleus accumbens basal ganglia	eqtl	3.8e-04	+1.46	19:1768721:G:A
Esophagus Muscularis	eqtl	1.0e-03	+0.25	19:2693968:CACTT:C
Colon Sigmoid	eqtl	4.4e-03	+0.99	19:2589737:C:T
Skin Sun Exposed Lower leg	eqtl	1.1e-02	-0.57	19:2729962:G:A
Thyroid	eqtl	1.6e-02	-0.30	19:2401118:C:G
Cells EBV-transformed lymphocytes	eqtl	2.3e-02	+0.26	19:2721993:A:C
Testis	eqtl	2.5e-02	-0.16	19:2695663:C:T
Colon Transverse	eqtl	4.1e-02	+0.45	19:2703291:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
178199	5.6593	967
178200	0.3868	194
178201	0.1211	53
178198	0.0558	16

Top tissues by expression

showing 100 of 244 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.45	gold quality
apex of heart	UBERON:0002098	97.88	gold quality
right frontal lobe	UBERON:0002810	96.12	gold quality
cortical plate	UBERON:0005343	96.11	gold quality
heart left ventricle	UBERON:0002084	95.92	gold quality
prefrontal cortex	UBERON:0000451	95.86	gold quality
cardiac ventricle	UBERON:0002082	95.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.76	gold quality
frontal cortex	UBERON:0001870	95.03	gold quality
right atrium auricular region	UBERON:0006631	95.03	gold quality
cardiac atrium	UBERON:0002081	94.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.72	gold quality
myocardium	UBERON:0002349	94.56	gold quality
neocortex	UBERON:0001950	94.50	gold quality
anterior cingulate cortex	UBERON:0009835	94.45	gold quality
ganglionic eminence	UBERON:0004023	93.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.02	gold quality
cerebellar cortex	UBERON:0002129	92.85	gold quality
cerebellar hemisphere	UBERON:0002245	92.80	gold quality
cerebral cortex	UBERON:0000956	92.68	gold quality
heart right ventricle	UBERON:0002080	92.43	gold quality
cerebellum	UBERON:0002037	92.35	gold quality
superior frontal gyrus	UBERON:0002661	92.24	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.10	gold quality
parietal lobe	UBERON:0001872	91.90	gold quality
postcentral gyrus	UBERON:0002581	91.75	gold quality
cerebellar vermis	UBERON:0004720	90.89	gold quality
heart	UBERON:0000948	90.65	gold quality
brain	UBERON:0000955	89.82	gold quality
forebrain	UBERON:0001890	89.81	gold quality
amygdala	UBERON:0001876	89.22	gold quality
occipital lobe	UBERON:0002021	88.85	gold quality
primary visual cortex	UBERON:0002436	88.67	gold quality
pons	UBERON:0000988	88.11	gold quality
Ammon’s horn	UBERON:0001954	87.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.78	gold quality
temporal lobe	UBERON:0001871	87.71	gold quality
putamen	UBERON:0001874	87.53	gold quality
middle temporal gyrus	UBERON:0002771	87.42	gold quality
caudate nucleus	UBERON:0001873	87.31	gold quality
nucleus accumbens	UBERON:0001882	87.19	gold quality
hypothalamus	UBERON:0001898	86.49	gold quality
ventricular zone	UBERON:0003053	86.17	gold quality
adenohypophysis	UBERON:0002196	85.86	gold quality
pituitary gland	UBERON:0000007	85.21	gold quality
substantia nigra	UBERON:0002038	85.19	gold quality
entorhinal cortex	UBERON:0002728	85.09	gold quality
midbrain	UBERON:0001891	84.77	gold quality
dorsal root ganglion	UBERON:0000044	83.32	gold quality
substantia nigra pars compacta	UBERON:0001965	81.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.12	gold quality
lower esophagus	UBERON:0013473	81.07	gold quality
ventral tegmental area	UBERON:0002691	80.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	80.40	gold quality
superior vestibular nucleus	UBERON:0007227	80.35	gold quality
tendon of biceps brachii	UBERON:0008188	80.21	silver quality
body of uterus	UBERON:0009853	79.84	gold quality
mucosa of stomach	UBERON:0001199	79.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.21	gold quality
vena cava	UBERON:0004087	79.18	gold quality
left uterine tube	UBERON:0001303	79.08	gold quality
islet of Langerhans	UBERON:0000006	78.46	gold quality
medulla oblongata	UBERON:0001896	78.04	gold quality
parotid gland	UBERON:0001831	77.97	gold quality
trigeminal ganglion	UBERON:0001675	77.50	gold quality
lateral globus pallidus	UBERON:0002476	77.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.22	gold quality
inferior vagus X ganglion	UBERON:0005363	76.92	gold quality
spinal cord	UBERON:0002240	76.51	gold quality
smooth muscle tissue	UBERON:0001135	75.90	gold quality
body of tongue	UBERON:0011876	75.86	gold quality
secondary oocyte	CL:0000655	75.27	gold quality
buccal mucosa cell	CL:0002336	74.74	gold quality
globus pallidus	UBERON:0001875	74.52	gold quality
upper arm skin	UBERON:0004263	74.06	gold quality
medial globus pallidus	UBERON:0002477	73.92	gold quality
myometrium	UBERON:0001296	73.89	gold quality
stromal cell of endometrium	CL:0002255	73.87	gold quality
pancreas	UBERON:0001264	73.47	gold quality
esophagus	UBERON:0001043	73.30	gold quality
pancreatic ductal cell	CL:0002079	73.28	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.75	gold quality
saliva-secreting gland	UBERON:0001044	71.94	gold quality
tongue	UBERON:0001723	71.85	gold quality
cartilage tissue	UBERON:0002418	71.80	silver quality
oocyte	CL:0000023	71.44	gold quality
body of pancreas	UBERON:0001150	71.07	gold quality
minor salivary gland	UBERON:0001830	70.87	gold quality
ectocervix	UBERON:0012249	70.74	gold quality
kidney epithelium	UBERON:0004819	70.53	gold quality
endocervix	UBERON:0000458	70.41	gold quality
adult organism	UBERON:0007023	70.36	gold quality
subthalamic nucleus	UBERON:0001906	70.22	silver quality
mouth mucosa	UBERON:0003729	70.20	gold quality
uterus	UBERON:0000995	70.16	gold quality
adult mammalian kidney	UBERON:0000082	70.12	gold quality
body of stomach	UBERON:0001161	69.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.25

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Postcentral gyrus	tissue	240.4
Hippocampus	tissue	80.5
Frontal cortex	tissue	66.0
Cerebral cortex	tissue	63.5
Somatosensory cortex	tissue	63.5
Caudate putamen	tissue	62.5
Heart muscle	tissue	62.3
Occipital cortex	tissue	59.7
Motor cortex	tissue	56.6
Superior colliculi	tissue	54.2
Prefrontal cortex	tissue	53.0
Thalamus	tissue	53.0
Locus coeruleus	tissue	50.8
Hippocampal formation	tissue	49.2
Entorhinal cortex	tissue	49.2
Retrosplenial and cingulate cortex	tissue	49.0
Tongue	tissue	48.4
Temporal cortex	tissue	48.3
Pons	tissue	46.0
Cerebellum	tissue	46.0
Retrosplenial cortex	tissue	45.0
Insular cortex	tissue	44.5
Midbrain	tissue	42.1
Nucleus accumbens	tissue	41.9
Ventral forebrain	tissue	36.2
Substantia nigra	tissue	33.1
Medulla oblongata	tissue	31.9
Septum	tissue	30.6
Amygdala	tissue	29.4
Basal ganglia	tissue	28.6
Hypothalamus	tissue	25.6
Putamen	tissue	23.2
Periaqueductal gray	tissue	22.8
Pituitary gland	tissue	21.3
Olfactory bulb	tissue	19.3
Spinal cord	tissue	18.2
Parathyroid gland	tissue	15.9
Retina	tissue	10.7
Corpus callosum	tissue	9.8
Smooth muscle	tissue	6.9
Endometrium 1	tissue	6.9
Choroid plexus	tissue	6.4
Salivary gland	tissue	6.3
Pancreas	tissue	6.3
Esophagus	tissue	5.1
Testis	tissue	4.0
Cervix	tissue	2.9
Prostate	tissue	2.6
Fallopian tube	tissue	2.4
Stomach 1	tissue	2.3
Epididymis	tissue	2.3
Adrenal gland	tissue	2.3
Vagina	tissue	2.2
Ovary	tissue	1.9
Kidney	tissue	1.9
Spleen	tissue	1.8
Seminal vesicle	tissue	1.7
Breast	tissue	1.5
Urinary bladder	tissue	1.4
Colon	tissue	1.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Precentral gyrus (229.6), Postcentral gyrus, middle (176.8), Supplementary motor cortex (176.3), Precentral gyrus, middle (165.8), Ventral posterolateral thalamic nucleus (159.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DIRAS1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 110 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164

Functional genomics

gnomAD constraint: pLI 0.351, LOEUF 0.907, missense Z 1.47 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000323469 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:2,717,213–2,717,379	84 / 79.9	1.05	no
19:2,717,380–2,717,806	128 / 205.3	0.62	no

Literature-anchored findings (GeneRIF, showing 8)

• a novel Ras-related protein and potential neural tumor suppressor (RIG) (PMID:12107278)
• DIRAS1 downregulation is associated with esophageal squamous cell carcinoma metastasis. (PMID:23436800)
• DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS (PMID:26814130)
• This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization. (PMID:28223533)
• Results show that DIRAS1 is frequently methylated in human colorectal cancer and the expression of DIRAS1 is silenced by promoter region methylation. (PMID:28491151)
• Analysis of the function and mechanism of DIRAS1 in osteosarcoma. (PMID:35413492)
• Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease. (PMID:37149695)
• M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells. (PMID:38372700)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	diras1b	ENSDARG00000009372
danio_rerio	diras1a	ENSDARG00000028066
mus_musculus	Diras1	ENSMUSG00000043670
rattus_norvegicus	Diras1	ENSRNOG00000029738

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

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
Pongo abelii	Q5R6S2	99.5%	Diamond
Macaca fascicularis	Q95KD9	99.5%	Diamond
Caenorhabditis elegans	Q09930	65.7%	Diamond
Dictyostelium discoideum	Q55BW0	51.2%	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
GNG7	protein-coding	2788
SLC39A3	protein-coding	29985
MIR7850	ncRNA	102465838
SGTA	protein-coding	6449
THOP1	protein-coding	7064
ZNF554	protein-coding	115196

Protein

Protein identifiers

GTP-binding protein Di-Ras1 — O95057 (reviewed: O95057)

Alternative names: Distinct subgroup of the Ras family member 1, Ras-related inhibitor of cell growth, Small GTP-binding tumor suppressor 1

All UniProt accessions (2): O95057, K7EN06

UniProt curated annotations — full annotation on UniProt →

Function. Displays low GTPase activity and exists predominantly in the GTP-bound form.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in heart and brain.

Similarity. Belongs to the small GTPase superfamily. Di-Ras family.

RefSeq proteins (1): NP_660156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

UniProt features (29 total): helix 8, strand 7, binding site 6, chain 1, propeptide 1, modified residue 1, lipid moiety-binding region 1, region of interest 1, turn 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2GF0	The crystal structure of the human DiRas1 GTPase in the inactive GDP bound state	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95057-F1	87.01	0.71

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; vesicles; nucleoplasm

Antibody reliability (HPA): 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 (6)

Position	Role
151	GTP
17–22	GTP
33–39	GTP
61–65	GTP
121–125	GTP
151–152	GTP

Post-translational modifications (2)

Type	Positions
Cysteine methyl ester	195
S-geranylgeranyl cysteine	195

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 130 (showing top): AP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TGACCTY_ERR1_Q2, MEF2_02, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, AP1_Q4_01, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, BACH2_01, GOBP_POSITIVE_REGULATION_OF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, TGANTCA_AP1_C, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, OUYANG_PROSTATE_CANCER_PROGRESSION_DN

GO Biological Process (2): small GTPase-mediated signal transduction (GO:0007264), signal transduction (GO:0007165)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

16 GO namespaces:

Category	Terms
intracellular signaling cassette	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay
GTP binding	MF	direct assay
GTPase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIRAS1	LRCH1	Q9Y2L9	518
DIRAS1	ZFAND4	Q86XD8	452
DIRAS1	VSNL1	P28677	390
DIRAS1	UBL4B	Q8N7F7	389
DIRAS1	RAP1GDS1	P52306	384
DIRAS1	WDR82	Q6UXN9	370
DIRAS1	CCNY	Q8ND76	370
DIRAS1	LRRC17	Q8N6Y2	369
DIRAS1	RARRES2	Q99969	369
DIRAS1	VENTX	O95231	366
DIRAS1	LCAT	P04180	364
DIRAS1	CREB3L1	Q96BA8	362
DIRAS1	PDP2	Q9P2J9	356
DIRAS1	OR51T1	Q8NGJ9	351
DIRAS1	OR2M2	Q96R28	344

IntAct

Human interaction partners of DIRAS1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
RAP1GDS1	association	0.640	8
PPP1R13B	physical association	0.560	3
TP53BP2	physical association	0.560	3
AKR1D1	association	0.530	1
UNC13B	association	0.500	2
NCOA7	physical association	0.400	2
ZNF274	physical association	0.400	1
SNX20	association	0.350	2
DIRAS2	association	0.350	1
GBA3	association	0.350	1
RAC2	association	0.350	1
SPATA13	association	0.350	1
TCEAL9	association	0.350	1

BioGRID (40 interactions; top human partners by supporting records): AKR1D1 (Affinity Capture-MS; 3 records), RAP1GDS1 (Affinity Capture-MS; 3 records), ARL4C (Affinity Capture-MS; 2 records), IL20RA (Affinity Capture-MS; 2 records), LINC01587 (Affinity Capture-MS; 2 records), MANSC1 (Affinity Capture-MS; 2 records), SNX20 (Affinity Capture-MS; 2 records), ALDOA (Cross-Linking-MS (XL-MS)), ALDOC (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex), C16orf72 (Positive Genetic), CDC123 (Affinity Capture-MS), DIRAS2 (Affinity Capture-MS), GBA3 (Affinity Capture-MS), NCOA7 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for DIRAS1: 20 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 100):

Position(s)	Effect	Δscore	Sites
19:2721302–2721303	donor_loss	1.0000	4
19:2717876–2717877	acceptor_loss	0.9900	6
19:2719390	donor_gain	0.9900
19:2717878	acceptor_gain	0.9700
19:2719410	donor_gain	0.9400
19:2721303	donor_loss	0.9300
19:2721318	donor_gain	0.9100
19:2719379	donor_gain	0.9000
19:2719389	donor_gain	0.8700
19:2719354	donor_gain	0.8600

AlphaMissense

673 missense substitutions predicted likely pathogenic (of 1,311 scored), across 143 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
M71	9	0.922	0.995
D61	8	0.998	0.999
D124	8	0.988	0.996
D42	8	0.985	0.995
F161	8	0.982	0.997
F68	8	0.967	1.000
N121	8	0.960	0.999
F32	8	0.959	1.000
F82	8	0.955	0.998
F13	8	0.926	0.982
D7	8	0.834	0.914
S21	7	0.991	0.997
K20	7	0.989	0.999
F27	7	0.986	0.995
F86	7	0.982	0.996
E41	7	0.967	0.990
K122	7	0.959	0.999
E148	7	0.945	0.977
W142	7	0.934	0.987
F146	7	0.901	0.972

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme, Skin Cutaneous Melanoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000531

Disease associations

OMIM: gene MIM:607862 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST90002381_230	Eosinophil count	3e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
Tobacco Smoke Pollution	increases expression	2
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Aldehydes	increases expression	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Mercury	decreases expression	1
Methapyrilene	decreases methylation	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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