DAB2IP

Summary

DAB2IP (DAB2 interacting protein, HGNC:17294) is a protein-coding gene on chromosome 9q33.2, encoding Disabled homolog 2-interacting protein (Q5VWQ8). Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.

DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. The DAB2IP gene is inactivated by methylation in prostate and breast cancers (Yano et al., 2005 [PubMed 15386433]).

Source: NCBI Gene 153090 — RefSeq curated summary.

At a glance

• GWAS associations: 26 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 226 total
• GTEx eGene: eQTL in 22 tissues, sQTL in 10 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.41 (moderately constrained)
• MANE Select transcript: NM_001395010
• Notable: 226 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17294
Approved symbol	DAB2IP
Name	DAB2 interacting protein
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	AF9Q34, DIP1/2, KIAA1743, AIP1
Ensembl gene	ENSG00000136848
Ensembl biotype	protein_coding
OMIM	609205
Entrez	153090

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000408936

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 5, TSL 5: 2

ENST00000408936, ENST00000259371, ENST00000309989, ENST00000436835, ENST00000459906, ENST00000465078, ENST00000487716, ENST00000489314, ENST00000648444, ENST00000648693, ENST00000699487, ENST00001069936, ENST00001110181

RefSeq mRNA: 3 — MANE Select: NM_001395010 NM_001395010, NM_032552, NM_138709

CCDS: CCDS6832, CCDS6833, CCDS94477

Canonical transcript exons

ENST00000408936 — 16 exons

Exon	Start	End
ENSE00001578649	121776198	121776391
ENSE00001579823	121766494	121766730
ENSE00001580667	121772607	121773495
ENSE00001580761	121774260	121774412
ENSE00001581915	121768432	121768633
ENSE00001584858	121759885	121760439
ENSE00001588943	121770546	121770724
ENSE00001670649	121699325	121699458
ENSE00001717577	121758898	121758996
ENSE00001745749	121781464	121781551
ENSE00001935432	121782331	121785530
ENSE00003493254	121763505	121763649
ENSE00003500573	121757013	121757166
ENSE00003515800	121763735	121763879
ENSE00003687903	121678678	121678781
ENSE00003978126	121651634	121651899

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8554 / max 352.7194, expressed in 1461 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DAB2IP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	5.7e-18	-0.32	9:121947091:A:G
Cells Cultured fibroblasts	eqtl	3.9e-16	+0.22	9:122063094:C:T
Ovary	eqtl	1.1e-13	+0.49	9:121797238:A:G
Testis	sqtl	4.3e-13	-1.69	9:121740928:G:A
Esophagus Muscularis	sqtl	9.9e-10	-1.03	9:121769205:G:C
Nerve Tibial	eqtl	2.7e-08	+0.15	9:121803541:T:C
Artery Tibial	sqtl	1.3e-06	-0.88	9:121769205:G:C
Adipose Subcutaneous	eqtl	2.2e-06	-0.16	9:121652472:A:G
Colon Sigmoid	sqtl	3.0e-06	-1.04	9:121713734:G:T
Brain Nucleus accumbens basal ganglia	eqtl	3.7e-06	+0.26	9:121852557:G:C
Adipose Subcutaneous	sqtl	6.3e-05	-0.78	9:121725216:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.5e-03	-0.33	9:122302921:C:T
Esophagus Muscularis	eqtl	2.1e-03	-0.26	9:121740928:G:A
Breast Mammary Tissue	sqtl	2.2e-03	-0.92	9:121769205:G:C
Adipose Visceral Omentum	eqtl	2.3e-03	-0.11	9:121653412:T:C
Muscle Skeletal	sqtl	3.2e-03	+0.23	9:121595191:A:G
Spleen	sqtl	3.6e-03	-1.89	9:122390342:G:A
Esophagus Gastroesophageal Junction	sqtl	5.3e-03	-0.97	9:121769205:G:C
Brain Frontal Cortex BA9	eqtl	5.6e-03	-0.53	9:120584375:G:A
Colon Transverse	sqtl	7.3e-03	-1.40	9:121432842:G:A

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
98382	3.2888	798
98384	2.5057	1030
98393	1.6628	767
98386	0.9383	638
98374	0.7208	271
98385	0.6693	397
98387	0.4742	260
98375	0.4016	273
98383	0.3751	181
98378	0.1913	91

Top tissues by expression

showing 100 of 264 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.00	gold quality
cerebellar hemisphere	UBERON:0002245	97.99	gold quality
cerebellar cortex	UBERON:0002129	97.93	gold quality
cerebellum	UBERON:0002037	97.71	gold quality
apex of heart	UBERON:0002098	94.21	gold quality
ileal mucosa	UBERON:0000331	94.00	gold quality
right coronary artery	UBERON:0001625	93.71	gold quality
sural nerve	UBERON:0015488	92.99	gold quality
putamen	UBERON:0001874	92.93	gold quality
descending thoracic aorta	UBERON:0002345	92.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.46	gold quality
tendon of biceps brachii	UBERON:0008188	92.33	gold quality
thoracic aorta	UBERON:0001515	92.20	gold quality
ascending aorta	UBERON:0001496	92.16	gold quality
aorta	UBERON:0000947	92.08	gold quality
popliteal artery	UBERON:0002250	92.07	gold quality
tibial artery	UBERON:0007610	92.06	gold quality
metanephros cortex	UBERON:0010533	92.05	gold quality
cerebellar vermis	UBERON:0004720	91.97	gold quality
body of uterus	UBERON:0009853	91.87	gold quality
tibialis anterior	UBERON:0001385	91.84	silver quality
caudate nucleus	UBERON:0001873	91.82	gold quality
right frontal lobe	UBERON:0002810	91.68	gold quality
transverse colon	UBERON:0001157	91.54	gold quality
oviduct epithelium	UBERON:0004804	91.49	gold quality
kidney epithelium	UBERON:0004819	91.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.37	gold quality
lower esophagus	UBERON:0013473	91.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.20	gold quality
left ventricle myocardium	UBERON:0006566	91.13	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	91.05	gold quality
anterior cingulate cortex	UBERON:0009835	90.94	gold quality
left coronary artery	UBERON:0001626	90.90	gold quality
gastrocnemius	UBERON:0001388	90.81	gold quality
coronary artery	UBERON:0001621	90.80	gold quality
cortical plate	UBERON:0005343	90.59	gold quality
muscle of leg	UBERON:0001383	90.58	gold quality
smooth muscle tissue	UBERON:0001135	90.45	gold quality
mucosa of stomach	UBERON:0001199	90.45	gold quality
heart left ventricle	UBERON:0002084	90.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.38	silver quality
adult mammalian kidney	UBERON:0000082	90.37	gold quality
right lung	UBERON:0002167	90.37	gold quality
upper arm skin	UBERON:0004263	90.35	silver quality
mucosa of transverse colon	UBERON:0004991	90.33	gold quality
nucleus accumbens	UBERON:0001882	90.23	gold quality
prefrontal cortex	UBERON:0000451	90.16	gold quality
body of stomach	UBERON:0001161	90.13	gold quality
cardiac ventricle	UBERON:0002082	90.06	gold quality
right ovary	UBERON:0002118	89.83	gold quality
colon	UBERON:0001155	89.81	gold quality
amygdala	UBERON:0001876	89.63	gold quality
upper lobe of left lung	UBERON:0008952	89.37	gold quality
large intestine	UBERON:0000059	89.36	gold quality
stomach	UBERON:0000945	89.33	gold quality
frontal cortex	UBERON:0001870	89.29	gold quality
stromal cell of endometrium	CL:0002255	89.25	gold quality
neocortex	UBERON:0001950	89.16	gold quality
renal medulla	UBERON:0000362	89.10	gold quality
skeletal muscle organ	UBERON:0014892	89.08	gold quality
upper lobe of lung	UBERON:0008948	89.06	gold quality
esophagus	UBERON:0001043	89.02	gold quality
skin of leg	UBERON:0001511	88.87	gold quality
heart	UBERON:0000948	88.79	gold quality
brain	UBERON:0000955	88.74	gold quality
left ovary	UBERON:0002119	88.72	gold quality
myometrium	UBERON:0001296	88.69	gold quality
fundus of stomach	UBERON:0001160	88.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.63	gold quality
left uterine tube	UBERON:0001303	88.47	gold quality
intestine	UBERON:0000160	88.29	gold quality
cortex of kidney	UBERON:0001225	88.22	gold quality
tibial nerve	UBERON:0001323	88.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.18	gold quality
cerebral cortex	UBERON:0000956	88.02	gold quality
forebrain	UBERON:0001890	87.92	gold quality
cardiac atrium	UBERON:0002081	87.91	gold quality
right atrium auricular region	UBERON:0006631	87.91	gold quality
fallopian tube	UBERON:0003889	87.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.56	gold quality
esophagus mucosa	UBERON:0002469	87.23	gold quality
Ammon’s horn	UBERON:0001954	87.20	gold quality
prostate gland	UBERON:0002367	87.11	gold quality
endocervix	UBERON:0000458	87.10	gold quality
ovary	UBERON:0000992	87.10	gold quality
hypothalamus	UBERON:0001898	87.03	gold quality
mammary duct	UBERON:0001765	86.95	gold quality
ectocervix	UBERON:0012249	86.87	gold quality
epithelium of mammary gland	UBERON:0003244	86.86	gold quality
skin of abdomen	UBERON:0001416	86.71	gold quality
right lobe of thyroid gland	UBERON:0001119	86.62	gold quality
kidney	UBERON:0002113	86.62	gold quality
zone of skin	UBERON:0000014	86.52	gold quality
temporal lobe	UBERON:0001871	86.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.50	gold quality
lower esophagus mucosa	UBERON:0035834	86.46	gold quality
postcentral gyrus	UBERON:0002581	86.45	gold quality
saphenous vein	UBERON:0007318	86.45	gold quality
vagina	UBERON:0000996	86.41	gold quality
omental fat pad	UBERON:0010414	86.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.96
E-ENAD-27	yes	6.13

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebellum	tissue	102.0
Hippocampus	tissue	68.5
Postcentral gyrus	tissue	67.6
Putamen	tissue	58.6
Nucleus accumbens	tissue	58.6
Locus coeruleus	tissue	53.8
Frontal cortex	tissue	47.6
Basal ganglia	tissue	43.6
Choroid plexus	tissue	42.9
Cerebral cortex	tissue	40.9
Motor cortex	tissue	40.9
Skeletal muscle	tissue	39.6
Somatosensory cortex	tissue	36.7
Prefrontal cortex	tissue	35.9
Insular cortex	tissue	35.6
Salivary gland	tissue	35.3
Retrosplenial cortex	tissue	35.1
Caudate putamen	tissue	33.3
Hippocampal formation	tissue	32.9
Thalamus	tissue	31.9
Retrosplenial and cingulate cortex	tissue	31.7
Occipital cortex	tissue	31.5
Temporal cortex	tissue	30.6
Entorhinal cortex	tissue	29.9
Ventral forebrain	tissue	29.8
Spinal cord	tissue	27.4
Midbrain	tissue	27.2
Superior colliculi	tissue	27.1
Substantia nigra	tissue	26.6
Amygdala	tissue	26.1
Medulla oblongata	tissue	25.5
Hypothalamus	tissue	25.1
Septum	tissue	24.6
Pons	tissue	24.2
Heart muscle	tissue	21.8
Seminal vesicle	tissue	20.5
Colon	tissue	20.4
Corpus callosum	tissue	20.4
Periaqueductal gray	tissue	19.5
Smooth muscle	tissue	19.3
Vagina	tissue	19.1
Small intestine	tissue	18.6
Adipose tissue	tissue	17.8
Ovary	tissue	17.5
Lung	tissue	17.3
Testis	tissue	17.1
Esophagus	tissue	17.1
Duodenum	tissue	16.8
Stomach 1	tissue	15.5
Spleen	tissue	15.4
Endometrium 1	tissue	15.3
Tongue	tissue	15.1
Pituitary gland	tissue	14.7
Fallopian tube	tissue	14.5
Rectum	tissue	13.5
Urinary bladder	tissue	13.4
Placenta	tissue	13.0
Gallbladder	tissue	12.3
Kidney	tissue	12.2
Skin 1	tissue	11.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (207.7), Vermis (188.4), Cerebellar cortex (177.7), Precentral gyrus (85.2), Ventromedial nucleus (83.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets:

Target	Regulation
KIT	Repression
PROX1	Repression
ZEB1	Repression

Upstream regulators (CollecTRI, top): EED, EZH2, SUZ12

miRNA regulators (miRDB)

Targeting DAB2IP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 187 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.407, missense Z 1.52 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000408936 splits into 3 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
9:121,651,776–121,757,114	283 / 237.0	1.19	no
9:121,757,115–121,772,659	517 / 748.6	0.69	no
9:121,772,660–121,782,495	600 / 659.1	0.91	no

Literature-anchored findings (GeneRIF, showing 40)

• Normal prostatic epithelial cells have elevated DAB2IP mRNA compared with cancer cells, which correlates with increased DAB2IP promoter activity. (PMID:11944990)
• Epigenetic regulation of this novel tumor suppressor gene in prostate cancer cell lines. (PMID:12446720)
• hDAB2IP methylation frequently is present in breast cancer and plays a key role in hDAB2IP inactivation. (PMID:15041729)
• AIP1 is a novel transducer in TNF-induced TRAF2-dependent activation of ASK1 that mediates a balance between JNK versus NF-kappaB signaling (PMID:15310755)
• Our results demonstrate that hDAB2IP methylation is frequently present in lung cancers and plays a key role in hDAB2IP silencing. (PMID:15386433)
• hDAB2IP gene is a target gene of Ezh2 in prostatic epithelium, which provides an underlying mechanism of the down-regulation of hDAB2IP gene in prostate cancer (PMID:15817459)
• promoter methylation of the hDAB2IP gene is involved in the progression of urinary bladder transitional cell carcinoma from a low to a high malignant potential (PMID:16328005)
• Analysis of SNPs indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer. (PMID:18073375)
• PP2A and DAB2IP cooperatively induce activation of ASK1-JNK signaling and vascular endothelial cell apoptosis. (PMID:18292600)
• Data show that DAB2IP is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest and is proapoptotic in response to stress, and that DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis. (PMID:19903888)
• Data show that loss of DAB2IP expression repressed E-cadherin and increased vimentin in both normal prostate epithelial and prostate carcinoma cells as well as in clinical prostate-cancer specimens. (PMID:20080667)
• functions as a signaling scaffold that coordinately regulates Ras and NF-kappaB through distinct domains to promote prostate cancer growth and metastasis (PMID:20154697)
• the A allele of rs7025486 on 9q33 was found to associate with abdominal aortic aneurysms; Rs7025486 is located within DAB2IP (PMID:20622881)
• A sequence variant in DAB2IP on chromosome 9 is associated with coronary heart disease (PMID:21444365)
• the 97906A variant genotypes are associated with the increased risk and early onset of lung cancer, particularly in males. (PMID:22046421)
• Low expression of DAB2IP contributes to malignant development and poor prognosis in hepatocellular carcinoma. (PMID:22168621)
• Studies indicate that DAB2IP and EZH2 are inversely expressed in medulloblastoma. (PMID:22696229)
• Both internalization and ASK1-interacting protein-1 association are required for TNFR2-dependent JNK and apoptotic signaling in endothelial cells. (PMID:22743059)
• Our results for the first time provided new insight into susceptibility factors of hDAB2IP gene variants in carcinogenesis of gastric cancer. (PMID:23246699)
• In this study, we show a novel function of DAB2IP in suppressing radiation-induced and DNA-PKcs-associated autophagy and promoting apoptosis in prostate cancer cells. (PMID:23308052)
• DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. (PMID:23558076)
• DAB2IP is a unique intrinsic androgen receptor modulator in normal cells, and likely can be further developed into a therapeutic agent for rpostate cancer. (PMID:23604126)
• This study unveils a new regulation of the Egr-1/Clusterin signaling network by DAB2IP. Loss of DAB2IP expression in CRPC cells signifies their chemoresistance (PMID:23838317)
• Human lymphatic endothelial cells with AIP1 small interfering RNA knockdown show attenuated VEGF-C-induced VEGFR-3 signaling. (PMID:24407031)
• downregulation of DAB2IP is associated with features of biologically aggressive urothelial carcinoma of the bladder and results in cell proliferation, migration, and invasion of bladder cancer. (PMID:24684735)
• our data indicate that a variety of pathways may pass through DAB2IP to govern cancer development (PMID:24912918)
• An inverse correlation between CD117 or ZEB1 and DAB2IP is also found in clinical specimens. (PMID:25043300)
• Immunohistochemical study exhibited an inverse correlation between DAB2IP and Skp2 protein expression in the prostate cancer tissue microarray. (PMID:25115390)
• Study showed that DAB2IP can be functionally inactivated by physical interaction with mutant p53 proteins with implications for the response of cancer cells to inflammatory cytokines. (PMID:25454946)
• strongly expressed in villi and extravillous trophoblasts but not in pre-eclampsia placentas (PMID:25604087)
• High glucose increases AIP1 expression and decreases the expression of HIF-1alpha and downstream molecules. Decreased HIF-1alpha signaling may be regulated by increased AIP1 under high glucose. (PMID:26021979)
• Snail and DAB2IP interact to regulate EMT, invasion and metastasis in colorectal cancer (PMID:26336990)
• DAB2IP could inhibit the phosphorylation and transactivation of STAT3, and then subsequently suppress the expression of Twist1 and its target gene P-glycoprotein, both of which were crucial for the pirarubicin chemoresistance. (PMID:26410305)
• Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy (PMID:26471467)
• Data show that colorectal cancer (CRC) patients with lower DAB2 interaction protein (DAB2IP) expression had shorter overall survival time. (PMID:26564738)
• Infiltrating T cells regulate ERbeta/DAB2IP signals in renal cell carcinoma. (PMID:26587829)
• DAB2IP appears to be a new prognostic/predictive marker for metastatic renal cell cancer (mRCC) patients, and its function provides a new insight into the molecular mechanisms of drug resistance to mTOR inhibitors, which also can be used to develop new strategies to overcome drug-resistant mRCC. (PMID:26876207)
• DAB2IP protein levels are higher in bladder cancer than in upper tract urothelial carcinoma and in superficial bladder cancer (PMID:27003158)
• Low DAB2IP expression is associated with neoplasms. (PMID:27036023)
• Data suggest that DAB2IP CpG1 methylation is a practical and repeatable biomarker for renal cell carcinoma (ccRCC), which can provide prognostic value that complements the current staging system. (PMID:27129174)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dab2ipa	ENSDARG00000069484
danio_rerio	dab2ipb	ENSDARG00000075110
mus_musculus	Dab2ip	ENSMUSG00000026883
rattus_norvegicus	Dab2ip	ENSRNOG00000055226
drosophila_melanogaster	raskol	FBGN0261570
caenorhabditis_elegans		WBGENE00001516

Paralogs (10): RASAL2 (ENSG00000075391), RASAL3 (ENSG00000105122), RASA4 (ENSG00000105808), RASAL1 (ENSG00000111344), RASA1 (ENSG00000145715), RASA2 (ENSG00000155903), RASA4B (ENSG00000170667), RASA3 (ENSG00000185989), NF1 (ENSG00000196712), SYNGAP1 (ENSG00000197283)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916851) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal Purkinje cell dendrite morphology	1
decreased physiological sensitivity to xenobiotic	1
decreased sensitivity to induced cell death	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	A6QQ91	83.4%	Diamond
Dictyostelium discoideum	Q54Y08	43.6%	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
STOM	protein-coding	2040
GGTA1	protein-coding	2681
TTLL11	protein-coding	158135
MIR4478	ncRNA	100616312

Protein

Protein identifiers

Disabled homolog 2-interacting protein — Q5VWQ8 (reviewed: Q5VWQ8)

Alternative names: ASK-interacting protein 1, DOC-2/DAB-2 interactive protein

All UniProt accessions (6): A0A3B3ITC7, A0A3B3ITG3, A0A3B3IUB7, A0A8V8TNA8, F6R503, Q5VWQ8

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Also plays a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to pro-inflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on ‘Ser-966’, leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Also mediates TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6), Ras and RAB40C. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Also functions as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively.

Subunit / interactions. On plasma membrane, exists in an inactive form complexed with TNFR1; in response to TNF, dissociates from TNFR1 complex, translocates to cytoplasm and forms part of an intracellular signaling complex comprising TRADD, RIPK1, TRAF2 and MAP3K5. Interacts with DAB1. Interacts (via NPXY motif) with DAB2 (via PID domain). Interacts (via PH domain) with ERN1. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF; this complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Interacts (via N-terminal domain) with JAK2; the interaction occurs in a IFNG/IFN-gamma-dependent manner and inhibits JAK2 autophosphorylation activity. Interacts (via C2 domain) with GSK3B; the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts (via proline-rich motif) with a regulatory p85 subunit (via SH3 domain) of the PI3K complex; the interaction inhibits the PI3K-AKT complex activity in a TNF-dependent manner in prostate cancer (PCa) cells. Interacts with AKT1; the interaction is increased in a TNF-induced manner. Interacts (via C2 domain and active form preferentially) with KDR/VEGFR2 (tyrosine-phosphorylated active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts (via N-terminus C2 domain) with MAP3K5 (‘Ser-966’ dephosphorylated form preferentially); the interaction occurs in a TNF-induced manner. Interacts (via Ras-GAP domain) with the catalytic subunit of protein phosphatase PP2A; the interaction occurs in resting endothelial cells, is further enhanced by TNF stimulation and is required to bridge PP2A to MAP3K5. Interacts (via C-terminus PER domain) with TRAF2 (via zinc fingers); the interaction occurs in a TNF-dependent manner. Interacts with 14-3-3 proteins; the interaction occurs in a TNF-dependent manner. Interacts (via Ras-GAP domain) with RIPK1 (via kinase domain); the interaction occurs in a TNF-dependent manner. Interacts with RAB40C; acts as a GAP for RAB40C.

Subcellular location. Cytoplasm. Cell membrane. Membrane. Cell projection. Dendrite.

Tissue specificity. Expressed in endothelial and vascular smooth muscle cells (VSMCs). Expressed in prostate epithelial but poorly in prostate cancer cells. Poorly expressed in medulloblastoma cells compared to cerebellar precursor proliferating progenitor cells (at protein level). Low expression in prostate. Down-regulated in prostate cancer.

Post-translational modifications. In response to TNF-induction, phosphorylated at Ser-728; phosphorylation leads to a conformational change, and thus, increases its association with 14-3-3 proteins, MAP3K5, RIPK1 and TRAF2 in endothelial cells; also stimulates regulatory p85 subunit sequestring and PI3K-p85 complex activity inhibition.

Disease relevance. A chromosomal aberration involving DAB2IP is found in a patient with acute myeloid leukemia (AML). Translocation t(9;11)(q34;q23) with KMT2A/MLL1. May give rise to a KMT2A/MLL1-DAB2IP fusion protein lacking the PH domain.

Domain organisation. The C2 and Ras-GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1. Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function.

Induction. Down-regulated in prostate cancer and medulloblastoma.

Miscellaneous. The DAB2IP gene is found epigenetically silenced in numerous aggressive cancers, like prostate cancers and medulloblastoma tumors. Epigenetic suppression of DAB2IP by EZH2 is a major mechanism of DAB2IP inactivation in human prostate cancer and increases metastatic potential.

Isoforms (5)

UniProt ID	Names	Canonical?
Q5VWQ8-1	1	yes
Q5VWQ8-2	2
Q5VWQ8-3	3
Q5VWQ8-4	4
Q5VWQ8-5	5

RefSeq proteins (3): NP_001381939, NP_115941, NP_619723 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001849	PH_domain	Domain
IPR001936	RasGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR021887	DAB2P_C	Domain
IPR023152	RasGAP_CS	Conserved_site
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039360	Ras_GTPase	Family
IPR057606	SynGAP1-like_PH	Domain

Pfam: PF00168, PF00616, PF12004, PF25321

UniProt features (44 total): compositionally biased region 10, region of interest 9, mutagenesis site 6, modified residue 4, splice variant 4, domain 3, sequence conflict 3, site 2, chain 1, coiled-coil region 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWQ8-F1	65.74	0.36

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes

Protein evidence: Evidence at protein level

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 (2)

Position	Role
172–173	breakpoint for translocation to form kmt2a/mll1-dab2ip
413	arginine finger; crucial for gtp hydrolysis by stabilizing the transition state

Post-translational modifications (4)

Type	Positions
Phosphoserine	728, 747, 978, 995

Mutagenesis-validated functional residues (6)

Position	Phenotype
228–230	reduces interaction with kdr/vegfr2. does not inhibit interaction with map3k5.
281–284	significantly reduces interaction with map3k5. does not reduce interaction with kdr/vegfr2.
413	decreased gap activity toward rab40c. does not inhibit interaction with map3k5. does not reduce gsk3b-induced beta-catenin transcription …
728	inhibits phosphorylation and tnf-induced map3k5 dephosphorylation. reduces interaction with 14-3-3 proteins, akt1, a regulatory p85 …
920–929	reduces interaction with a regulatory p85 subunit of the pi3k complex. inhibits map3k5 active form increase, akt1 active form decrease …
935	does not reduce interaction with 14-3-3 proteins.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-5658442	Regulation of RAS by GAPs	curated
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-5673001	RAF/MAP kinase cascade	—
R-HSA-162582	Signal Transduction	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (67): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), inflammatory response (GO:0006954), negative regulation of cell population proliferation (GO:0008285), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), negative regulation of endothelial cell migration (GO:0010596), negative regulation of epithelial cell migration (GO:0010633), negative regulation of epithelial to mesenchymal transition (GO:0010719), positive regulation of neuron projection development (GO:0010976), negative regulation of angiogenesis (GO:0016525), cell motility involved in cerebral cortex radial glia guided migration (GO:0021814), layer formation in cerebral cortex (GO:0021819), negative regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030948), positive regulation of protein-containing complex assembly (GO:0031334), tumor necrosis factor-mediated signaling pathway (GO:0033209), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), negative regulation of GTPase activity (GO:0034260), cellular response to unfolded protein (GO:0034620), tube formation (GO:0035148), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), vascular endothelial growth factor receptor-2 signaling pathway (GO:0036324), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of protein catabolic process (GO:0042177), positive regulation of apoptotic process (GO:0043065), regulation of GTPase activity (GO:0043087), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), regulation of protein-containing complex assembly (GO:0043254), negative regulation of MAPK cascade (GO:0043409), positive regulation of MAPK cascade (GO:0043410), positive regulation of GTPase activity (GO:0043547), innate immune response (GO:0045087), positive regulation of protein catabolic process (GO:0045732), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), negative regulation of Ras protein signal transduction (GO:0046580), negative regulation of fibroblast proliferation (GO:0048147), neuron projection morphogenesis (GO:0048812), negative regulation of epithelial cell proliferation (GO:0050680), regulation of cell cycle (GO:0051726), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), negative regulation of G0 to G1 transition (GO:0070317), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), endothelial cell apoptotic process (GO:0072577), negative regulation of canonical Wnt signaling pathway (GO:0090090), positive regulation of synapse maturation (GO:0090129), lipid droplet formation (GO:0140042), positive regulation of dendrite development (GO:1900006), regulation of p38MAPK cascade (GO:1900744), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), positive regulation of proteasomal protein catabolic process (GO:1901800)

+7 more (showing top 60).

GO Molecular Function (21): GTPase activator activity (GO:0005096), death receptor binding (GO:0005123), SH3 domain binding (GO:0017124), kinase binding (GO:0019900), protein kinase binding (GO:0019901), mitogen-activated protein kinase kinase binding (GO:0031434), mitogen-activated protein kinase kinase kinase binding (GO:0031435), phosphatidylinositol-3-phosphate binding (GO:0032266), signaling adaptor activity (GO:0035591), phosphatidylinositol 3-kinase regulatory subunit binding (GO:0036312), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), vascular endothelial growth factor receptor 2 binding (GO:0043184), protein serine/threonine kinase activator activity (GO:0043539), phosphatidylinositol 3-kinase binding (GO:0043548), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), protein phosphatase 2A binding (GO:0051721), phosphatidylinositol-4-phosphate binding (GO:0070273), 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle (GO:0030139), axon (GO:0030424), dendrite (GO:0030425), neuronal cell body membrane (GO:0032809), neuronal cell body (GO:0043025), cerebellar mossy fiber (GO:0044300), climbing fiber (GO:0044301), parallel fiber (GO:1990032), AIP1-IRE1 complex (GO:1990597)

Reactome top-level categories

4 top-level categories:

Category	Pathways
RAF/MAP kinase cascade	1
MAPK1/MAPK3 signaling	1
Signal Transduction	1
MAPK family signaling cascades	1

GO top-level categories

showing 60 of 82 GO namespaces:

Category	Terms
anatomical structure formation involved in morphogenesis	3
protein binding	3
cellular anatomical structure	3
axon	3
negative regulation of cell migration	2
negative regulation of multicellular organismal process	2
cerebral cortex radial glia-guided migration	2
negative regulation of signal transduction	2
GTPase activity	2
intracellular anatomical structure	2
protein kinase binding	2
phosphatidylinositol phosphate binding	2
neuron projection	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
defense response	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
extrinsic apoptotic signaling pathway	1
regulation of endothelial cell migration	1
endothelial cell migration	1
epithelial cell migration	1
regulation of epithelial cell migration	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell motility	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
negative regulation of immune system process	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
response to unfolded protein	1
cellular response to topologically incorrect protein	1
tube morphogenesis	1
signal transduction	1
enzyme activator activity	1
GTPase regulator activity	1
tumor necrosis factor receptor superfamily binding	1
protein domain specific binding	1
enzyme binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 63 of 101 annotations. The rest are phylogenetic / computational / electronic (IEA).

showing 60 of 63 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to interleukin-1	BP	direct assay
cellular response to lipopolysaccharide	BP	direct assay
cellular response to tumor necrosis factor	BP	direct assay
cellular response to vascular endothelial growth factor stimulus	BP	direct assay
extrinsic apoptotic signaling pathway via death domain receptors	BP	mutant phenotype
intracellular signal transduction	BP	mutant phenotype
lipid droplet formation	BP	mutant phenotype
negative regulation of DNA-templated transcription	BP	mutant phenotype
negative regulation of ERK1 and ERK2 cascade	BP	direct assay
negative regulation of G0 to G1 transition	BP	direct assay
negative regulation of MAPK cascade	BP	mutant phenotype
negative regulation of Ras protein signal transduction	BP	mutant phenotype
negative regulation of angiogenesis	BP	direct assay
negative regulation of canonical NF-kappaB signal transduction	BP	direct assay
negative regulation of canonical Wnt signaling pathway	BP	mutant phenotype
negative regulation of cell population proliferation	BP	direct assay
negative regulation of endothelial cell migration	BP	mutant phenotype
negative regulation of epithelial cell migration	BP	mutant phenotype
negative regulation of epithelial cell proliferation	BP	mutant phenotype
negative regulation of epithelial to mesenchymal transition	BP	direct assay
negative regulation of non-canonical NF-kappaB signal transduction	BP	mutant phenotype
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	direct assay
negative regulation of protein catabolic process	BP	direct assay
negative regulation of toll-like receptor 4 signaling pathway	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
negative regulation of vascular endothelial growth factor receptor signaling pathway	BP	mutant phenotype
positive regulation of GTPase activity	BP	mutant phenotype
positive regulation of JNK cascade	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of apoptotic process	BP	direct assay
positive regulation of apoptotic signaling pathway	BP	direct assay
positive regulation of proteasomal protein catabolic process	BP	mutant phenotype
positive regulation of protein-containing complex assembly	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of cell cycle	BP	direct assay
regulation of protein-containing complex assembly	BP	direct assay
tube formation	BP	mutant phenotype
tumor necrosis factor-mediated signaling pathway	BP	direct assay
AIP1-IRE1 complex	CC	direct assay
cytoplasm	CC	direct assay
endocytic vesicle	CC	direct assay
membrane	CC	direct assay
plasma membrane	CC	direct assay
14-3-3 protein binding	MF	direct assay
GTPase activator activity	MF	mutant phenotype
SH3 domain binding	MF	direct assay
cadherin binding	MF	high-throughput assay
death receptor binding	MF	physical interaction
identical protein binding	MF	physical interaction
kinase binding	MF	physical interaction
mitogen-activated protein kinase kinase binding	MF	physical interaction
mitogen-activated protein kinase kinase kinase binding	MF	physical interaction
phosphatidylinositol 3-kinase binding	MF	direct assay
phosphatidylinositol 3-kinase regulatory subunit binding	MF	direct assay
phosphatidylinositol-3-phosphate binding	MF	direct assay
phosphatidylinositol-4-phosphate binding	MF	direct assay
protein homodimerization activity	MF	physical interaction
protein kinase binding	MF	direct assay
protein phosphatase 2A binding	MF	physical interaction
protein serine/threonine kinase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,108 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAB2IP	DAB2	P98082	733
DAB2IP	EZH2	Q15910	731
DAB2IP	MAP3K5	Q99683	670
DAB2IP	SUZ12	Q15022	640
DAB2IP	LXN	Q9BS40	555
DAB2IP	H3C1	P02295	497
DAB2IP	H3-4	Q16695	497
DAB2IP	H3-7	Q5TEC6	497
DAB2IP	H3-5	Q6NXT2	497
DAB2IP	H3C14	Q71DI3	497
DAB2IP	H3-3A	P06351	496
DAB2IP	TTLL11	Q8NHH1	487
DAB2IP	RIPK1	Q13546	466
DAB2IP	CDKN2B	P42772	454
DAB2IP	TRADD	Q15628	450

IntAct

Human interaction partners of DAB2IP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
MAP3K5	physical association	0.510	3
GSK3B	physical association	0.400	2
SMARCA2	physical association	0.370	1
DDX3Y	association	0.350	1
MCC	association	0.350	1
CBY1	physical association	0.000	1

BioGRID (133 interactions; top human partners by supporting records): MAP3K5 (Affinity Capture-Western; 6 records), AKT1 (Affinity Capture-Western; 3 records), ANKS1A (Affinity Capture-MS; 3 records), MCC (Affinity Capture-MS; 3 records), PIK3R1 (Reconstituted Complex; 3 records), RFPL3 (Affinity Capture-MS; 3 records), TRAF2 (Affinity Capture-Western; 3 records), USP10 (Affinity Capture-MS; 3 records), CD83 (Affinity Capture-MS; 2 records), CDC20 (Affinity Capture-Western; 2 records), CGN (Affinity Capture-MS; 2 records), CLIP1 (Affinity Capture-MS; 2 records), DAB2 (Affinity Capture-Western; 2 records), RASAL2 (Affinity Capture-MS; 2 records), RBX1 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 28 of 29 signaling interactions:

A	Effect	B	Mechanism
DAB2	“up-regulates activity”	DAB2IP	binding
DAB2IP	“down-regulates activity”	HRAS	“gtpase-activating protein”
DAB2IP	“down-regulates activity”	KRAS	“gtpase-activating protein”
DAB2IP	“down-regulates activity”	NRAS	“gtpase-activating protein”
DAB2IP	“up-regulates activity”	MAP3K5	binding
DAB2IP	“up-regulates activity”	ERN1	binding
DAB2IP	“down-regulates activity”	PIK3CA	binding
DAB2IP	“down-regulates activity”	AKT	binding
DAB2IP	“up-regulates activity”	GSK3B	binding
DAB2IP	“up-regulates activity”	PP2Ca_R1A_Bd	binding
DAB2IP	“down-regulates activity”	PIK3R1	binding
DAB2IP	“down-regulates activity”	AR	binding
DAB2IP	“down-regulates activity”	JAK2	binding
DAB2IP	“down-regulates activity”	STAT3	binding
RIPK1	“up-regulates activity”	DAB2IP	phosphorylation
DAB2IP	“down-regulates quantity by repression”	PROX1	“transcriptional regulation”
DAB2IP	“down-regulates quantity by destabilization”	HIF1A
DAB2IP	“down-regulates quantity by repression”	KIT	“transcriptional regulation”
DAB2IP	“up-regulates activity”	GATA1	binding
DAB2IP	“down-regulates quantity by repression”	ZEB1	“transcriptional regulation”
DAB2IP	“down-regulates activity”	14-3-3	binding
FBXW7	“down-regulates quantity by destabilization”	DAB2IP	ubiquitination
SKP2	“down-regulates quantity by destabilization”	DAB2IP	ubiquitination
SMURF1	“down-regulates quantity by destabilization”	DAB2IP	ubiquitination
DAB2IP	down-regulates	Cell_migration
DAB2IP	down-regulates	Survival
AKT1	“down-regulates activity”	DAB2IP	phosphorylation
DAB2IP	“down-regulates quantity”	CTNNB1	relocalization

Disease & clinical

Genetic variants

Variant evidence for DAB2IP: 226 ClinVar records (0 pathogenic / likely pathogenic); 26 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	189
Likely benign	9
Benign	7

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,925):

Position(s)	Effect	Δscore	Sites
9:121757167–121757168	donor_loss	1.0000	5
9:121758895	acceptor_gain	1.0000
9:121758896–121758897	acceptor_loss	1.0000	5
9:121758997–121758998	donor_loss	1.0000	5
9:121759878	acceptor_gain	1.0000
9:121759883–121759884	acceptor_loss	1.0000	6
9:121763494	acceptor_gain	1.0000
9:121763503–121763504	acceptor_loss	1.0000	6
9:121763650–121763651	donor_loss	1.0000	3
9:121763726	acceptor_gain	1.0000

AlphaMissense

3,832 missense substitutions predicted likely pathogenic (of 7,744 scored), across 844 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
M577	9	0.954	0.999
M1099	9	0.951	0.999
M1120	9	0.944	0.996
M473	9	0.943	0.994
M588	9	0.941	0.994
M342	9	0.920	0.997
M574	9	0.891	0.998
M1107	9	0.881	0.992
M398	9	0.878	0.991
M194	9	0.844	0.976
F171	8	0.998	1.000
F412	8	0.996	0.999
F497	8	0.996	1.000
D612	8	0.996	0.999
D206	8	0.994	0.999
N415	8	0.993	0.999
F522	8	0.992	0.999
F182	8	0.991	1.000
F489	8	0.991	0.999
F567	8	0.991	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.12e-10
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	3.19e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000453
Glioblastoma Multiforme (validation)	favorable	0.000983

Disease associations

OMIM: gene MIM:609205 | disease phenotypes:

GWAS associations

26 associations:

Study	Trait	p-value
GCST012490_315	Femur bone mineral density x serum urate levels interaction	4e-15
GCST010866_134	Coronary artery disease	1e-13
GCST90000025_21	Appendicular lean mass	5e-13
GCST003877_4	Abdominal aortic aneurysm	2e-11
GCST010480_6	Coronary artery disease	7e-11
GCST90020027_555	Waist-hip index	2e-10
GCST000727_2	Abdominal aortic aneurysm	5e-10
GCST90020025_1184	Waist-to-hip ratio adjusted for BMI	6e-10
GCST005195_12	Coronary artery disease	8e-10
GCST007446_24	vWF levels	3e-9
GCST008835_1	Squamous cell lung carcinoma	3e-9
GCST007446_3	vWF levels	4e-9
GCST007446_47	vWF levels	4e-9
GCST007446_84	vWF levels	4e-9
GCST012490_205	Femur bone mineral density x serum urate levels interaction	4e-9
GCST005196_125	Coronary artery disease	8e-9
GCST90020026_264	Hip index	2e-8
GCST010479_38	Coronary artery disease	4e-8
GCST011365_84	Myocardial infarction	4e-8
GCST001588_11	Periodontal microbiota	5e-7
GCST001995_4	Adverse response to chemotherapy (neutropenia/leucopenia) (docetaxel)	6e-7
GCST001859_17	Thiazide-induced adverse metabolic effects in hypertensive patients	2e-6
GCST008403_8	Arterial stiffness index	5e-6
GCST009391_356	Metabolite levels	8e-6
GCST001921_4	Heart rate	9e-6
GCST002119_17	Metabolite levels (X-11787)	9e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005276	hydroxy-leucine measurement
EFO:0004517	arterial stiffness measurement
EFO:0010384	phosphatidylcholine 38:2 measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523330 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.92	Kd	120.5	nM	CHEMBL4579552
6.82	Ki	150	nM	CHEMBL4579552
6.82	Kd	151	nM	CHEMBL4579552
6.81	Ki	155	nM	CHEMBL4469853
6.41	Ki	390	nM	CHEMBL4469619
6.11	Ki	779	nM	CHEMBL1344136
5.90	Ki	1260	nM	CHEMBL467987
5.72	Ki	1920	nM	CHEMBL1380684

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases methylation, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects expression	3
bisphenol A	increases expression, affects methylation	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	increases methylation, decreases methylation	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation, increases methylation	1
coumarin	decreases phosphorylation	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression	1
Chelating Agents	decreases expression, affects binding	1
Cisplatin	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Ethinyl Estradiol	affects expression	1
Methapyrilene	increases methylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4417843	Binding	Binding affinity to human Dab2 DH domain (33 to 191 residues) expressed in Escherichia coli BL21 (DE3) RIL cells pre-incubated for 10 to 15 mins before fluorescently labeled peptide addition by fluorescence polarization assay	Dab2 inhibitors for the prevention and treatment of cystic fibrosis

Clinical trials (associated diseases)

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

showing 60 of 281 trials:

NCT	Phase	Status	Title
NCT01485211	Phase 4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	Phase 4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	Phase 4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	Phase 4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	Phase 4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	Phase 4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT07629557	Phase 4	RECRUITING	Evaluate the Safety and Feasibility of Same-Day Bilateral Epithelium-On Corneal Cross-Linking for Keratoconus
NCT00371202	Phase 3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	Phase 3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	Phase 3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	Phase 3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	Phase 3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	Phase 3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	Phase 3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	Phase 3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	Phase 3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	Phase 3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	Phase 3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	Phase 3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	Phase 3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	Phase 3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	Phase 3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	Phase 3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	Phase 3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	Phase 3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	Phase 3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	Phase 3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	Phase 3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	Phase 3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	Phase 3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	Phase 3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	Phase 3	COMPLETED	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	Phase 3	COMPLETED	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06450470	Phase 3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	Phase 3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	Phase 3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases
NCT07135167	Phase 3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT00409955	Phase 2	COMPLETED	Lamellar Transplant With Lyophilized Corneas
NCT00925327	Phase 2	UNKNOWN	Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking for Compassionate Treatment in Pediatric Patients With Progressive Keratoconus
NCT01143389	Phase 2	COMPLETED	Corneal Crosslinking in Patients With Keratoconus and Post-Refractive Ectasia
NCT01181219	Phase 2	COMPLETED	Transepithelial Corneal Collagen Cross-linking (CXL) in Treatment of Keratoconus
NCT01325298	Phase 2	UNKNOWN	UVA-Riboflavin Crosslinking Treatment of Corneal Ectasia
NCT01809977	Phase 2	COMPLETED	Comparison of Partial Removal and Total Removal of the Corneal Epithelium on Keratoconus
NCT01843101	Phase 2	COMPLETED	Investigation of Different Scanning Protocols for 3 Dimensional High-resolution Imaging of the Human Cornea With Optical Coherence Tomography (OCT) - A Pilot Study
NCT01869517	Phase 2	UNKNOWN	Myoring Versus Keraring Implantation for Keratoconus
NCT01956474	Phase 2	TERMINATED	CXL-04 A Study of Collagen Crosslinking With Ultraviolet-A in Asymmetric Corneas
NCT02514200	Phase 2	UNKNOWN	Treatment of Keratoconus With Advanced CXL-II
NCT02762253	Phase 2	TERMINATED	Study of the Safety and Effectiveness of Photochemically Induced Collagen Cross-Linking in Eyes With Keratoconus.
NCT02827747	Phase 2	WITHDRAWN	The Role of Antioxidant Supplementation in Keratoconus Patients
NCT02834260	Phase 2	COMPLETED	Immunosuppression During Penetrating Keratoplasty, Using a Subconjunctival Implant Releasing Dexamethasone : Tolerance and Safety Pilot Study
NCT03029104	Phase 2	TERMINATED	Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
NCT04094090	Phase 2	RECRUITING	Safety and Effectiveness of the PXL-Platinum 330 System for Corneal Cross-Linking in Eyes With Corneal Ectasia
NCT04240457	Phase 2	TERMINATED	Safety and Efficacy of Corneal Crosslinking Using the PXL-Platinum 330 for Eyes With Corneal Ectatic Conditions
NCT04811924	Phase 2	TERMINATED	The Effect of Mitomycin C on Corneal Haze and Scarring After Corneal Crosslinking in Keratoconus Patients
NCT05279157	Phase 2	COMPLETED	Autologous Adipose-Derived Adult Stem Cell Implantation for Corneal Diseases (ADASCs-CT-CD)
NCT05516004	Phase 2	RECRUITING	Safety and Effectiveness of the PXL-Platinum 330 System for Cornea Crosslinking in Eyes With Cornea Thinning
NCT07400952	Phase 2	RECRUITING	Placebo-controlled Study to Evaluate the Safety and Efficacy of GLK-221 Ophthalmic Solution in Subjects With Keratoconus
NCT00566605	Phase 1	UNKNOWN	Outcomes in a Comparison of Manual Penetrating Keratoplasty and the IntraLase® Enabled Keratoplasty
NCT02009709	Phase 1	UNKNOWN	Study of the Safety and Effectiveness of Collagen Cross-Linking at an Irradiance of 9 mW/cm2 and 18 mW/cm2
NCT02625467	Phase 1	COMPLETED	Treatment of Keratoconus With PALK Versus PK

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DAB2IP across ~30M SureChEMBL compounds — explore on Sugi Predict.