DAB1

Summary

DAB1 (DAB adaptor protein 1, HGNC:2661) is a protein-coding gene on chromosome 1p32.2, encoding Disabled homolog 1 (O75553). Signaling adapter of the reelin-mediated signaling pathway, which regulates the migration and differentiation of postmitotic neurons during brain development.

The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain.

Source: NCBI Gene 1600 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 37 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 29
• Clinical variants (ClinVar): 180 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_001365792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2661
Approved symbol	DAB1
Name	DAB adaptor protein 1
Location	1p32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173406
Ensembl biotype	protein_coding
OMIM	603448
Entrez	1600

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000332102, ENST00000371230, ENST00000371231, ENST00000371232, ENST00000371236, ENST00000414851, ENST00000420954, ENST00000473821, ENST00000477280, ENST00000485760, ENST00000489267, ENST00000853968, ENST00000853969, ENST00000929475, ENST00000929476, ENST00000959326, ENST00000959327, ENST00000959328, ENST00000959329, ENST00000959330, ENST00000959331, ENST00000959332

RefSeq mRNA: 8 — MANE Select: NM_001365792 NM_001353983, NM_001353985, NM_001353986, NM_001365792, NM_001365793, NM_001379461, NM_001379462, NM_021080

CCDS: CCDS607

Canonical transcript exons

ENST00000371236 — 15 exons

Exon	Start	End
ENSE00001178937	57062884	57062943
ENSE00001454705	56994778	56998128
ENSE00003490930	57014883	57015431
ENSE00003511220	57071522	57071641
ENSE00003527836	57136543	57136641
ENSE00003547715	57069360	57069425
ENSE00003557991	57011145	57011272
ENSE00003565613	57071023	57071061
ENSE00003580392	57290964	57291166
ENSE00003594871	57010680	57010790
ENSE00003605379	57023531	57023639
ENSE00003607182	57025981	57026043
ENSE00003646130	57145290	57145429
ENSE00003680734	57072283	57072414
ENSE00003908676	57423930	57424060

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 98.19.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8691 / max 224.8485, expressed in 585 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12565	9.9520	1738
12559	1.6655	312
12548	1.1953	417
12547	0.5874	265
12558	0.4772	190
12551	0.2872	120
12560	0.2338	99
12549	0.1689	81
12552	0.1072	48
12546	0.1029	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.19	gold quality
jejunal mucosa	UBERON:0000399	89.22	gold quality
sural nerve	UBERON:0015488	88.05	gold quality
ventricular zone	UBERON:0003053	85.57	gold quality
cerebellar cortex	UBERON:0002129	84.56	gold quality
cerebellar hemisphere	UBERON:0002245	84.50	gold quality
ganglionic eminence	UBERON:0004023	84.46	gold quality
cerebellum	UBERON:0002037	83.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.45	gold quality
cerebellar vermis	UBERON:0004720	81.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.88	gold quality
duodenum	UBERON:0002114	80.69	gold quality
entorhinal cortex	UBERON:0002728	79.42	gold quality
ileal mucosa	UBERON:0000331	79.10	silver quality
middle temporal gyrus	UBERON:0002771	78.49	gold quality
primary visual cortex	UBERON:0002436	77.36	gold quality
Ammon’s horn	UBERON:0001954	76.92	gold quality
small intestine	UBERON:0002108	76.76	gold quality
endothelial cell	CL:0000115	76.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.48	gold quality
anterior cingulate cortex	UBERON:0009835	76.47	gold quality
cingulate cortex	UBERON:0003027	76.41	gold quality
seminal vesicle	UBERON:0000998	76.24	gold quality
temporal lobe	UBERON:0001871	75.59	gold quality
cerebral cortex	UBERON:0000956	75.30	gold quality
right lobe of liver	UBERON:0001114	75.09	gold quality
prefrontal cortex	UBERON:0000451	74.87	gold quality
neocortex	UBERON:0001950	74.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	92.61
E-HCAD-25	yes	46.57
E-CURD-114	yes	6.71
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, SCX, TBXT, TOP2B

miRNA regulators (miRDB)

29 targeting DAB1, 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-6759-5P	99.99	66.54	785
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-581	98.39	67.42	835
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-656-5P	96.82	67.67	372
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-6796-5P	95.37	66.08	1120

Literature-anchored findings (GeneRIF, showing 37)

• This gene, is an intracellular adaptor of the Reelin pathway and reveals unusual complexity in human and mouse. (PMID:12446734)
• involvement of disabled homolog 1 in neurogenesis (PMID:12581169)
• RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function. (PMID:12834112)
• Dab1 immunoreactivity is found in certain populations of amacrine cells of the retina, with lobular appendages in the outer half of the inner plexiform layer (IPL) and a bushy, smooth dendritic tree in the inner half of the IPL. (PMID:14961563)
• significantly lower levels of disabled homolog 1 gene transcripts were detected in gangliogliomas compared to controls (PMID:15175076)
• Dab1 regulates both cell surface expression and internalization of Reelin receptors (PMID:15718228)
• phosphoinositide-binding region within Dab1 PTB domain is required for membrane localization and basal tyrosine phosphorylation of Dab1 (PMID:15883038)
• After Reelin binds to the receptors, Disabled-1 becomes phosphorylated on tyrosine residues, initiating a signaling cascade that includes activation of Src-family kinases and Akt. (PMID:16481437)
• The effect of Dab1 on APP and apoEr2 processing in transfected cells and primary neurons is reported. (PMID:16951405)
• results suggest that the mouse ortholog is a nucleocytoplasmic shuttling protein (PMID:17062576)
• DAB1 phosphorylation occurs solely in the segment spanning the 5th and 6th reelin repeats. (PMID:17548821)
• Cul5 plays an essential role in regulating neuron migrations during cortical development, possibly by opposing a promigratory effect of Dab1. (PMID:17974915)
• Resides within an unstable common fragile site region and might play a role in human tumorigenesis. (PMID:18008369)
• Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2. (PMID:18089558)
• ligation of ApoER2 by APC signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and inactivation of GSK3beta, thereby contributing to APC’s beneficial effects on cells. (PMID:19116273)
• Thus, the present observations suggest a correlation between Dab1 phosphorylation, Abeta deposition and PrP(sc) type in sCJD. (PMID:19853035)
• Fe65 and Dab1 compete for binding to APP. Dab1 significantly decreased the amount of APP bound to LRP and the level of secreted APP and APP-CTF in LRP expressing cells (PMID:20568118)
• Dab1, an essential component of the reelin pathway, is required for glia-independent somal translocation in the neocortex. (PMID:21315259)
• we report for the first time, that DAB1 is significantly up-regulated in human frontal cortex brain samples of Alzheimer disease patients (PMID:21453247)
• alternative splicing of Dab1 is conserved in avian and mammalian species, with Dab1-L driving SFK phosphorylation in both species (PMID:22163036)
• show that Reelin-stimulated Notch-1 activation is dependent on Reelin signaling (PMID:22394407)
• Variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1, was examined. (PMID:22419519)
• The finding of this study suggested that variations in DAB1 involved in the Reelin signaling pathway might contribute to genetic susceptibility to autism with Chinese Han decent. (PMID:23333377)
• results of this study demonstrated the presence of reelin, its receptors VLDLR and ApoER2 as well as Dab1 in the ENS and might indicate a novel role of the reelin system in regulating neuronal plasticity and pre-synaptic functions in the ENS. (PMID:24844606)
• this study is the first to provide genetic evidence for DAB1 as a candidate AD liability/protection gene, although the strength of the contribution of DAB1 may differ among populations (PMID:26028559)
• Study shows that early neural cells transiently express Reelin at the time they leave the presumptive olfactory/vomeronasal epithelium and that Dab 1 is present in the migratory cell mass and in the presumptive ensheathing cells in the absence of reelin. (PMID:26270645)
• these results establish an unstable repeat insertion in DAB1 as a cause of cerebellar degeneration. (PMID:28686858)
• In intestine a truncated Dab1 variant transmits the reelin signal and may play a role in clathrin-mediated apical endocytosis and in the control of cell-to-cell junction assembly. Dab1 variant may be a nucleocytoplasmic shuttling protein, inferred from its sequence and nuclear location. (PMID:29470947)
• our findings provide direct evidence for the impaired Reelin-DAB1 transduction cascade in a patient with deleterious variants in the RELN gene, suggest, for the first time, an abnormal interplay between Reelin-DAB1 and mTORC1 signaling pathways in a patient with nonsyndromic ASD (PMID:29969175)
• Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer. (PMID:30484953)
• the repeat region associated with SCA37 is highly polymorphic, mutable, and unstable, and the AluJb seems to have had a role in these features, as the (ATTTC)n insertion was probably originated by one or more T>C substitutions in the Alu element. (PMID:30588707)
• The appearance of DAB1 and Reelin during fetal kidney development confirms their potential significant role in the formation of kidney structure or function. High DAB1 expression in the DCT implies its regulatory role in tubular formation or function maintenance during development. (PMID:31894918)
• Inhibition of microRNA-300 inhibits cell adhesion, migration, and invasion of prostate cancer cells by promoting the expression of DAB1. (PMID:33064976)
• Disabled 1 Is Part of a Signaling Pathway Activated by Epidermal Growth Factor Receptor. (PMID:33572344)
• Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer’s disease pathogenesis. (PMID:35977442)
• ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer’s disease. (PMID:38093390)
• The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1). (PMID:38919020)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	dab1b	ENSDARG00000003290
danio_rerio	dab1a	ENSDARG00000059939
mus_musculus	Dab1	ENSMUSG00000028519
rattus_norvegicus	Dab1	ENSRNOG00000007410
drosophila_melanogaster	Dab	FBGN0000414
drosophila_melanogaster	numb	FBGN0002973
drosophila_melanogaster	CG8312	FBGN0037720
drosophila_melanogaster	Aplip1	FBGN0040281
drosophila_melanogaster	CG42673	FBGN0261555
caenorhabditis_elegans		WBGENE00000894
caenorhabditis_elegans		WBGENE00001116
caenorhabditis_elegans		WBGENE00002176
caenorhabditis_elegans		WBGENE00003830
caenorhabditis_elegans		WBGENE00009930

Paralogs (11): MAPK8IP2 (ENSG00000008735), NUMBL (ENSG00000105245), MAPK8IP1 (ENSG00000121653), NUMB (ENSG00000133961), GULP1 (ENSG00000144366), DAB2 (ENSG00000153071), LDLRAP1 (ENSG00000157978), FAM43B (ENSG00000183114), FAM43A (ENSG00000185112), NOS1AP (ENSG00000198929), C1orf226 (ENSG00000239887)

Protein

Protein identifiers

Disabled homolog 1 — O75553 (reviewed: O75553)

All UniProt accessions (4): A0A075B6G7, A0A3G6VF52, O75553, X6R4J9

UniProt curated annotations — full annotation on UniProt →

Function. Signaling adapter of the reelin-mediated signaling pathway, which regulates the migration and differentiation of postmitotic neurons during brain development. Mediates intracellular transduction of Reelin signaling following reelin (RELN)-binding to its receptor: acts by docking proteins through its phosphotyrosine residues and PID domain.

Subunit / interactions. Associates with the SH2 domains of SRC, FYN and ABL. Interacts (phosphorylated on tyrosine residues) with CRK and CRKL (via respective SH2 domain). Interacts with SIAH1, LRP8 and VLDLR. Interacts with LRP1. Interacts with APLP1 (via NPXY motif). Interacts with DAB2IP. Interacts with ZSWIM8.

Subcellular location. Cytoplasm.

Tissue specificity. Mainly expressed in brain.

Post-translational modifications. Phosphorylated by FYN on Tyr-198 and Tyr-220 upon reelin induction in embryonic neurons. Also phosphorylated on Ser-524 independently of reelin signaling. Ubiquitinated by various cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes) following ligand-binding and phosphorylation, leading to its degradation. Ubiquitinated by the ECS(SOCS7) complex in the cortical plate of the developing cerebral cortex following ligand-binding and phosphorylation by FYN, leading to its degradation by the proteasome. Recognized by ZSWIM8 through a disorder targets misorder mechanism that eliminates misfolded DAB1 via ubiquitination and proteasomal degradation.

Disease relevance. Spinocerebellar ataxia 37 (SCA37) [MIM:615945] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA37 is an autosomal dominant form characterized by adult-onset of slowly progressive gait instability, frequent falls, and dysarthria associated with cerebellar atrophy on brain imaging. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PID domain specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins.

Isoforms (6)

UniProt ID	Names	Canonical?
O75553-1	DAB588	yes
O75553-2	DAB213
O75553-3	DAB469
O75553-4	DAB537
O75553-5	DAB553
O75553-6	DAB555

RefSeq proteins (8): NP_001340912, NP_001340914, NP_001340915, NP_001352721, NP_001352722, NP_001366390, NP_001366391, NP_066566 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR048559	DAB1/2_SBM	Conserved_site
IPR048561	Dab_PTB	Domain

Pfam: PF00640, PF21792

UniProt features (32 total): sequence conflict 10, splice variant 6, compositionally biased region 5, modified residue 4, region of interest 4, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75553-F1	59.20	0.25

Functional residue map

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

Post-translational modifications (4): 198, 220, 232, 524

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8866376	Reelin signalling pathway

MSigDB gene sets: 255 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, MYAATNNNNNNNGGC_UNKNOWN, GOBP_HINDBRAIN_DEVELOPMENT, RRAGTTGT_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_BEHAVIOR, NKX25_02, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOBP_ADULT_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION

GO Biological Process (31): neuron migration (GO:0001764), negative regulation of cell adhesion (GO:0007162), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), small GTPase-mediated signal transduction (GO:0007264), axonogenesis (GO:0007409), adult walking behavior (GO:0007628), dendrite development (GO:0016358), ventral spinal cord development (GO:0021517), cerebellum structural organization (GO:0021589), hippocampus development (GO:0021766), cell-cell adhesion involved in neuronal-glial interactions involved in cerebral cortex radial glia guided migration (GO:0021813), layer formation in cerebral cortex (GO:0021819), radial glia guided migration of Purkinje cell (GO:0021942), central nervous system neuron differentiation (GO:0021953), reelin-mediated signaling pathway (GO:0038026), positive regulation of neuron differentiation (GO:0045666), negative regulation of receptor signaling pathway via JAK-STAT (GO:0046426), astrocyte differentiation (GO:0048708), negative regulation of astrocyte differentiation (GO:0048712), negative regulation of axonogenesis (GO:0050771), Golgi localization (GO:0051645), regulation of synapse maturation (GO:0090128), lateral motor column neuron migration (GO:0097477), radial glia-guided pyramidal neuron migration (GO:0140650), cell adhesion (GO:0007155), nervous system development (GO:0007399), cerebral cortex cell migration (GO:0021795), cerebral cortex radially oriented cell migration (GO:0021799), cell differentiation (GO:0030154), neuron differentiation (GO:0030182), motor neuron migration (GO:0097475)

GO Molecular Function (2): signaling adaptor activity (GO:0035591), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
cellular anatomical structure	3
central nervous system development	2
neuron differentiation	2
cytoplasm	2
cell migration	1
generation of neurons	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
cell surface receptor signaling pathway via STAT	1
intracellular signaling cassette	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
adult locomotory behavior	1
walking behavior	1
neuron projection development	1
spinal cord development	1
hindbrain structural organization	1
cerebellum morphogenesis	1
anatomical structure arrangement	1
pallium development	1
limbic system development	1
neuronal-glial interaction involved in cerebral cortex radial glia guided migration	1
cell-cell adhesion	1
cerebral cortex radial glia-guided migration	1
anatomical structure formation involved in morphogenesis	1
hindbrain radial glia guided cell migration	1
cell surface receptor signaling pathway	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of receptor signaling pathway via STAT	1
glial cell differentiation	1
negative regulation of glial cell differentiation	1
astrocyte differentiation	1
regulation of astrocyte differentiation	1
axonogenesis	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAB1	VLDLR	P98155	724
DAB1	LRP8	Q14114	674
DAB1	RELN	P78509	636
DAB1	ATXN10	Q9UBB4	610
DAB1	PRKCG	P05129	574
DAB1	SAMD12	Q8N8I0	573
DAB1	ATXN7	O15265	507
DAB1	RFC1	P35251	506
DAB1	CRKL	P46109	504
DAB1	NOP56	O00567	479
DAB1	STARD7	Q9NQZ5	475
DAB1	PPP2R2B	Q00005	447
DAB1	CRK	P46108	421
DAB1	KCNC3	Q14003	419
DAB1	FYN	P06241	414

IntAct

155 interactions, top by confidence:

A	B	Type	Score
DAB1	LNX1	psi-mi:“MI:0915”(physical association)	0.740
LNX1	DAB1	psi-mi:“MI:0915”(physical association)	0.740
VENTX	DAB1	psi-mi:“MI:0915”(physical association)	0.670
DAB1	MBNL1	psi-mi:“MI:0915”(physical association)	0.670
MBNL1	DAB1	psi-mi:“MI:0915”(physical association)	0.670
DAB1	VENTX	psi-mi:“MI:0915”(physical association)	0.670
DAB1	ROR2	psi-mi:“MI:0915”(physical association)	0.560
DAB1	SIRPB1	psi-mi:“MI:0915”(physical association)	0.560
DAB1	BHLHE40	psi-mi:“MI:0915”(physical association)	0.560
RBFOX2	DAB1	psi-mi:“MI:0915”(physical association)	0.560
DAB1	HYAL3	psi-mi:“MI:0915”(physical association)	0.560
	DAB1	psi-mi:“MI:0915”(physical association)	0.560
DAB1		psi-mi:“MI:0915”(physical association)	0.560
DAB1	TMTC3	psi-mi:“MI:0915”(physical association)	0.560
DAB1	ZBTB32	psi-mi:“MI:0915”(physical association)	0.560
DAB1	SNRPB	psi-mi:“MI:0915”(physical association)	0.560
PRR20C	DAB1	psi-mi:“MI:0915”(physical association)	0.560
DAB1	PPIG	psi-mi:“MI:0915”(physical association)	0.560
DAB1	PIN1	psi-mi:“MI:0915”(physical association)	0.560
DAB1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	DAB1	psi-mi:“MI:0915”(physical association)	0.560
LGALS9B	DAB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (116): DAB1 (Two-hybrid), MBNL1 (Two-hybrid), ROR2 (Two-hybrid), PIN1 (Two-hybrid), SNRPB (Two-hybrid), TCEA2 (Two-hybrid), HYAL3 (Two-hybrid), BHLHE40 (Two-hybrid), PPIG (Two-hybrid), MAGED1 (Two-hybrid), DAZAP2 (Two-hybrid), SERF2 (Two-hybrid), SIRPB1 (Two-hybrid), ARID5A (Two-hybrid), CLASRP (Two-hybrid)

ESM2 similar proteins: A1L1I3, A5PKW4, O08919, O70405, O75385, O75420, O75553, P16554, P42128, P49757, P53814, P85037, P97318, P98081, Q04637, Q2LC84, Q3UCQ1, Q4KMP7, Q5DTT2, Q5I1X5, Q5RBR0, Q5VZ18, Q69ZH9, Q69ZI1, Q7TN02, Q7Z6J0, Q80VC9, Q80XI3, Q80Z38, Q86V15, Q8BGT6, Q8BHL3, Q8BSD5, Q8C120, Q8CI12, Q8IY33, Q8K4J6, Q8N3F8, Q8TEH3, Q8TEJ3

Diamond homologs: O75553, O88797, P49757, P97318, P98078, P98081, P98082, Q2LC84, Q8CJH2, Q9BGX5, Q9QZS3, A1L1I3, O08919, Q5PQS4, Q9Y6R0, P16554, Q5SW96, Q67FQ3, Q8C142, Q9XTY6

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
DAB1	up-regulates	NOTCH1	binding
TOP2B	“up-regulates quantity by expression”	DAB1	“transcriptional regulation”
FYN	“down-regulates activity”	DAB1	phosphorylation
SRC	“up-regulates activity”	DAB1	phosphorylation
PTPRG	“down-regulates activity”	DAB1	dephosphorylation
SOCS4	“down-regulates quantity by destabilization”	DAB1	binding
CUL5	“down-regulates quantity by destabilization”	DAB1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	6	13.2×	1e-03
mRNA processing	5	9.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	86
Likely benign	28
Benign	38

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
430691	NC_000001.10:g.57832716_57832797ins[(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90]	Pathogenic
1027503	NM_001365792.1(DAB1):c.763C>T (p.Pro255Ser)	Likely pathogenic

SpliceAI

5249 predictions. Top by Δscore:

Variant	Effect	Δscore
1:57011143:A:AC	donor_gain	1.0000
1:57011144:C:CC	donor_gain	1.0000
1:57011144:CAG:C	donor_gain	1.0000
1:57011285:C:CT	acceptor_gain	1.0000
1:57044470:C:CT	donor_gain	1.0000
1:57044471:T:TT	donor_gain	1.0000
1:57069442:C:CT	acceptor_gain	1.0000
1:57069443:A:T	acceptor_gain	1.0000
1:57069461:G:C	acceptor_gain	1.0000
1:57069461:G:GC	acceptor_gain	1.0000
1:57071549:AT:A	donor_gain	1.0000
1:57072275:ATACT:A	donor_loss	1.0000
1:57072277:ACT:A	donor_loss	1.0000
1:57072278:CTC:C	donor_loss	1.0000
1:57072280:CA:C	donor_loss	1.0000
1:57072281:A:AC	donor_gain	1.0000
1:57072281:A:AT	donor_loss	1.0000
1:57072281:ACCG:A	donor_gain	1.0000
1:57072282:C:CC	donor_gain	1.0000
1:57072282:CCG:C	donor_gain	1.0000
1:57072282:CCGC:C	donor_gain	1.0000
1:57136537:ACTT:A	donor_loss	1.0000
1:57136538:CTT:C	donor_loss	1.0000
1:57136539:TTA:T	donor_loss	1.0000
1:57136540:TAC:T	donor_loss	1.0000
1:57136541:A:AC	donor_gain	1.0000
1:57136541:AC:A	donor_gain	1.0000
1:57136541:ACC:A	donor_gain	1.0000
1:57136542:C:A	donor_loss	1.0000
1:57136542:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005057 (1:57257303 C>T), RS1000010638 (1:58216139 T>A,C), RS1000011750 (1:58125628 C>G,T), RS1000012083 (1:57327455 C>A,G), RS1000012160 (1:57056283 C>T), RS1000016774 (1:57871161 T>C,G), RS1000017459 (1:57248793 T>A,C), RS1000021187 (1:57124696 T>G), RS1000024169 (1:57369341 A>G), RS1000024520 (1:57288935 T>C), RS1000025371 (1:57563524 G>A), RS1000026262 (1:57592807 C>G), RS1000026721 (1:58132382 C>G,T), RS1000027238 (1:58221321 C>T), RS1000029212 (1:57580562 A>G)

Disease associations

OMIM: gene MIM:603448 | disease phenotypes: MIM:108600, MIM:615945, MIM:604229

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 37	Strong	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (4): spastic ataxia (MONDO:0017845), spinocerebellar ataxia type 37 (MONDO:0014410), Peters anomaly (MONDO:0011414), neurodevelopmental disorder (MONDO:0700092)

Orphanet (4): Spastic ataxia (Orphanet:316226), Spinocerebellar ataxia type 37 (Orphanet:363710), Peters anomaly (Orphanet:708), Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

29 total (30 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000549	Abnormal conjugate eye movement
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0002015	Dysphagia
HP:0002075	Dysdiadochokinesis
HP:0002078	Truncal ataxia
HP:0002167	Abnormal speech pattern
HP:0002168	Scanning speech
HP:0002317	Unsteady gait
HP:0002359	Frequent falls
HP:0002396	Cogwheel rigidity
HP:0002406	Limb dysmetria
HP:0002527	Falls
HP:0003474	Somatic sensory dysfunction
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003677	Slowly progressive
HP:0006855	Cerebellar vermis atrophy
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0100275	Diffuse cerebellar atrophy
HP:0000659	Peters anomaly

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000939_2	Kawasaki disease	1.000000e-06
GCST001534_4	Immune reponse to smallpox (secreted IL-10)	3.000000e-07
GCST001875_10	Pubertal anthropometrics	2.000000e-06
GCST001958_22	Bulimia nervosa	2.000000e-06
GCST002360_9	Plasma amyloid beta peptide concentrations (ABx-40)	5.000000e-06
GCST003245_1	White matter hyperintensities in ischemic stroke	2.000000e-07
GCST005582_1	Coronary artery disease	2.000000e-14
GCST006136_2	Alzheimer’s disease progression score	8.000000e-07
GCST007006_1	Logical memory (delayed recall) in normal cognition	4.000000e-08
GCST007323_100	Risk-taking tendency (4-domain principal component model)	3.000000e-09
GCST007387_28	Insomnia symptoms (never/rarely vs. sometimes/usually)	2.000000e-08
GCST007388_21	Insomnia symptoms (never/rarely vs. usually)	1.000000e-11
GCST007673_12	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-06
GCST008151_118	Waist circumference	3.000000e-06
GCST008160_70	Waist circumference	3.000000e-06
GCST008309_9	Cardiac troponin-I levels	1.000000e-07
GCST009189_2	Lateral orbital frontal cortex volume	5.000000e-06
GCST009524_277	Household income (MTAG)	3.000000e-09
GCST010315_4	Serum linoleic acid concentration in metabolic syndrome	3.000000e-10
GCST010696_21	Cortical thickness (min-P)	3.000000e-10
GCST010697_9	Cortical surface area (min-P)	2.000000e-10
GCST010698_47	Subcortical volume (min-P)	4.000000e-11
GCST010699_23	Brain morphology (min-P)	1.000000e-09
GCST010700_54	Cortical thickness (MOSTest)	6.000000e-10
GCST010701_120	Cortical surface area (MOSTest)	6.000000e-11
GCST010702_57	Subcortical volume (MOSTest)	4.000000e-12
GCST010703_31	Brain morphology (MOSTest)	6.000000e-09
GCST010796_1146	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST90000047_3	Age at first sexual intercourse	1.000000e-08

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005659	plasma beta-amyloid 1-40 measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0004874	memory performance
EFO:0008579	risk-taking behaviour
EFO:0007876	insomnia measurement
EFO:0009603	stroke outcome severity measurement
EFO:0010071	cardiac troponin I measurement
EFO:0009695	household income
EFO:0006807	linoleic acid measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004327	electrocardiography
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C537884	Peters anomaly (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
fluorene-9-bisphenol	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Fonofos	increases methylation	1
Endosulfan	affects cotreatment, decreases expression	1
Estradiol	affects expression	1
Mercury	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge