DAAM1

Summary

DAAM1 (dishevelled associated activator of morphogenesis 1, HGNC:18142) is a protein-coding gene on chromosome 14q23.1, encoding Disheveled-associated activator of morphogenesis 1 (Q9Y4D1). Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation.

Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins.

Source: NCBI Gene 23002 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 150 total — 1 pathogenic
• MANE Select transcript: NM_001270520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18142
Approved symbol	DAAM1
Name	dishevelled associated activator of morphogenesis 1
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0666
Ensembl gene	ENSG00000100592
Ensembl biotype	protein_coding
OMIM	606626
Entrez	23002

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 retained_intron, 4 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000360909, ENST00000395125, ENST00000553307, ENST00000553472, ENST00000553966, ENST00000554459, ENST00000555651, ENST00000556135, ENST00000556596, ENST00000556894, ENST00000557029, ENST00000557327, ENST00000557628

RefSeq mRNA: 2 — MANE Select: NM_001270520 NM_001270520, NM_014992

CCDS: CCDS58323, CCDS9737

Canonical transcript exons

ENST00000360909 — 25 exons

Exon	Start	End
ENSE00000658110	59291217	59291306
ENSE00000658111	59315280	59315351
ENSE00000658113	59322892	59323225
ENSE00000658117	59326510	59326648
ENSE00000867425	59324128	59324238
ENSE00000867427	59324351	59324454
ENSE00000867429	59325960	59326077
ENSE00000867431	59326933	59326991
ENSE00000867432	59330501	59330688
ENSE00000867433	59331209	59331508
ENSE00001094734	59355165	59355333
ENSE00001275479	59263441	59263660
ENSE00002432951	59188667	59188768
ENSE00003511755	59359397	59359504
ENSE00003522142	59368650	59371403
ENSE00003527515	59320490	59320584
ENSE00003570862	59360802	59360862
ENSE00003592681	59367429	59367599
ENSE00003592854	59353876	59353964
ENSE00003604718	59363651	59363782
ENSE00003646760	59352526	59352632
ENSE00003649886	59325664	59325730
ENSE00003656401	59331813	59331920
ENSE00003669521	59347539	59347623
ENSE00003685507	59340074	59340180

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5696 / max 1205.7036, expressed in 1776 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139842	23.5696	1776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.07	gold quality
secondary oocyte	CL:0000655	98.91	gold quality
pigmented layer of retina	UBERON:0001782	97.88	gold quality
cervix squamous epithelium	UBERON:0006922	97.48	gold quality
tongue squamous epithelium	UBERON:0006919	97.00	gold quality
nipple	UBERON:0002030	96.88	gold quality
upper arm skin	UBERON:0004263	96.82	gold quality
penis	UBERON:0000989	96.46	gold quality
upper leg skin	UBERON:0004262	96.43	gold quality
skin of hip	UBERON:0001554	96.22	gold quality
mammalian vulva	UBERON:0000997	96.11	gold quality
cortical plate	UBERON:0005343	96.08	gold quality
saphenous vein	UBERON:0007318	95.97	gold quality
choroid plexus epithelium	UBERON:0003911	95.83	gold quality
squamous epithelium	UBERON:0006914	95.50	gold quality
cervix epithelium	UBERON:0004801	95.32	gold quality
esophagus squamous epithelium	UBERON:0006920	95.09	gold quality
pharyngeal mucosa	UBERON:0000355	95.05	gold quality
hair follicle	UBERON:0002073	94.87	gold quality
myocardium	UBERON:0002349	94.63	gold quality
right coronary artery	UBERON:0001625	94.52	gold quality
gingiva	UBERON:0001828	94.46	gold quality
oral cavity	UBERON:0000167	94.35	gold quality
gingival epithelium	UBERON:0001949	94.35	gold quality
heart right ventricle	UBERON:0002080	94.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.22	gold quality
oviduct epithelium	UBERON:0004804	94.18	gold quality
cardiac atrium	UBERON:0002081	93.71	gold quality
zone of skin	UBERON:0000014	93.54	gold quality
urethra	UBERON:0000057	93.54	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	91.42
E-HCAD-6	yes	41.70
E-HCAD-5	yes	16.68
E-GEOD-135922	yes	15.62
E-CURD-114	yes	6.69
E-GEOD-124858	no	320.32
E-MTAB-9801	no	153.46
E-GEOD-93593	no	12.36
E-MTAB-9067	no	4.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3

miRNA regulators (miRDB)

223 targeting DAAM1, 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-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372

Literature-anchored findings (GeneRIF, showing 31)

• DAAM1 was shown to bind to the SH3 domain of CIP4 in vivo. (PMID:16630611)
• Results report that Profilin1 is an effector downstream of Daam1 required for cytoskeletal changes during gastrulation. (PMID:17021034)
• The DAAM1 FH2 domain structure, determined at 2.25 A resolution, and DAAM1 actin binding activity (PMID:17482208)
• Crystal structure of human DAAM1 formin homology 2 domain (PMID:17986009)
• a carboxyl-terminal binding partner, Dvl, has a role in activation of Daam1 (PMID:18162551)
• mDia1 and Daam1 are platelet actin assembly factors having distinct efficiencies, and they are directly regulated by Rho GTPases (PMID:18218625)
• Fli-I promotes the GTP-bound active Rho-mediated relief of the autoinhibition of Daam1 and mDia1. Thus, Fli-I is a novel positive regulator of Rho-induced linear actin assembly mediated by DRFs. (PMID:20223827)
• DAAM1 regulates endothelial cell growth through MT stabilization in a cell type-selective manner (PMID:20351293)
• DAAM1 is a formin required for centrosome re-orientation during cell migration. (PMID:20927366)
• Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA. (PMID:22655072)
• A developmentally restricted function of miR-490 and its putative DAAM1 target are associated with exaggerated megakaryocytopoiesis and/or proplatelet formation. (PMID:22869791)
• Daam1 plays a dual role in the phagocytic uptake of borreliae. (PMID:24696301)
• Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of planar cell polarity-signaling pathway-dependent activation in endothelial cells. (PMID:26792835)
• DAAM1 organizes actin filaments into a nodal complex (PMID:27760153)
• Kank1 plays a crucial role in regulating the activity of RhoA through retrieving excess Daam1 and balancing the activities of RhoA and its effectors. (PMID:28284839)
• High Daam-1 expression may upregulate the Wnt/PCP pathway and cause idiopathic pulmonary arterial hypertension (PMID:28288669)
• Results provide evidence that Daam1 activates RhoA to regulate Wnt5ainduced glioblastoma cell invasion. (PMID:29207169)
• miR-613 is involved in cell migration and invasion of triple-negative breast cancer cells via targeting Daam1/RhoA signaling pathway. (PMID:29339084)
• coiling phagocytosis is a mechanism for borrelial internalization by neuroglial cells mediated by Daam1 (PMID:29746581)
• Integrin alphavbeta3-associated DAAM1 is essential for collagen-induced invadopodia extension and cell haptotaxis in breast cancer cells (PMID:29752407)
• Our data suggest that miR-208-5p/DAAM1 axis participates in ovarian cancer migration and invasion. (PMID:31104928)
• findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasivenes (PMID:31406243)
• Overexpressed DAAM1 correlates with metastasis and predicts poor prognosis in breast cancer. (PMID:31757662)
• Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells. (PMID:31894282)
• DAAM1 and PREP are involved in human spermatogenesis. (PMID:31972124)
• Dishevelled Associated Activator Of Morphogenesis (DAAM) Facilitates Invasion of Hepatocellular Carcinoma by Upregulating Hypoxia-Inducible Factor 1alpha (HIF-1alpha) Expression. (PMID:32772041)
• SNHG15 facilitated malignant behaviors of oral squamous cell carcinoma through targeting miR-188-5p/DAAM1. (PMID:33742497)
• Disheveled-associated activator of morphogenesis 2 promotes invasion of colorectal cancer by activating PAK1 and promoting MMP7 expression. (PMID:33974241)
• Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders. (PMID:34360857)
• The formin DAAM1 regulates the deubiquitinase activity of USP10 and integrin homeostasis. (PMID:37562219)
• Formin Binding Protein 1 (FNBP1) regulates non-canonical Wnt signaling and vertebrate gastrulation. (PMID:38945423)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	daam1b	ENSDARG00000009689
danio_rerio	daam1a	ENSDARG00000015059
mus_musculus	Daam1	ENSMUSG00000034574
rattus_norvegicus	Daam1	ENSRNOG00000004345
drosophila_melanogaster	DAAM	FBGN0025641
caenorhabditis_elegans		WBGENE00018976

Paralogs (18): FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

Disheveled-associated activator of morphogenesis 1 — Q9Y4D1 (reviewed: Q9Y4D1)

All UniProt accessions (2): Q9Y4D1, G3V275

UniProt curated annotations — full annotation on UniProt →

Function. Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation. May play a role as a scaffolding protein to recruit Rho-GDP and Rho-GEF, thereby enhancing Rho-GTP formation. Can direct nucleation and elongation of new actin filaments. Involved in building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Together with DAAM2, required for myocardial maturation and sarcomere assembly. During cell division, may regulate RHOA activation that signals spindle orientation and chromosomal segregation.

Subunit / interactions. Homodimer. Interacts with CIP4, FNBP1 and FNBP1L. Interacts with the SH3 domains of Abl, BTK, endophilin, spectrin and SRC. Binds specifically to GTP-bound CDC42 and RHOA. Interacts with INTU; INTU mediates the indirect interaction between DAAM1 and NPHP4. Interacts (via coiled coil domain) with KANK1 (via coiled coil domain).

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body.

Tissue specificity. Expressed in all tissues examined.

Domain organisation. The C-terminal DAD domain may participate in intramolecular interactions with the N-terminus. The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y4D1-1	1	yes
Q9Y4D1-2	2
Q9Y4D1-3	3

RefSeq proteins (2): NP_001257449, NP_055807 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010472	FH3_dom	Domain
IPR010473	GTPase-bd	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR014767	DAD_dom	Domain
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR051425	Formin_Homology	Family

Pfam: PF02181, PF06367, PF06371

UniProt features (53 total): helix 23, region of interest 5, domain 4, compositionally biased region 4, splice variant 4, strand 4, modified residue 3, turn 2, chain 1, coiled-coil region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2J1D	X-RAY DIFFRACTION	2.25
2Z6E	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4D1-F1	80.52	0.46

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 (3): 34, 1027, 1030

Mutagenesis-validated functional residues (1):

Position	Phenotype
698	abolishes actin-binding.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-4086400	PCP/CE pathway
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle

MSigDB gene sets: 386 (showing top): MYOGENIN_Q6, TGCGCANK_UNKNOWN, CCAWYNNGAAR_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TGACCTY_ERR1_Q2, HNF1_Q6, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, ATGTTAA_MIR302C

GO Biological Process (5): Wnt signaling pathway, planar cell polarity pathway (GO:0060071), presynaptic actin cytoskeleton organization (GO:0099140), cellular component organization (GO:0016043), Wnt signaling pathway (GO:0016055), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (4): actin binding (GO:0003779), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (13): stress fiber (GO:0001725), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), motile cilium (GO:0031514), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	4
Beta-catenin independent WNT signaling	1
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	2
cilium	2
synapse	2
non-canonical Wnt signaling pathway	1
actin cytoskeleton organization	1
presynaptic cytoskeleton organization	1
cellular component organization or biogenesis	1
cell surface receptor signaling pathway	1
cytoskeleton organization	1
actin filament-based process	1
cytoskeletal protein binding	1
GTPase binding	1
protein binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
membrane	1
cell periphery	1
microtubule organizing center	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

2058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAAM1	DVL1	O14640	998
DAAM1	SRRM4	A7MD48	899
DAAM1	RHOA	P06749	838
DAAM1	ARHGEF19	Q8IW93	827
DAAM1	DVL2	O14641	781
DAAM1	PRICKLE1	Q96MT3	727
DAAM1	ARHGEF11	O15085	719
DAAM1	CELSR1	Q9NYQ6	716
DAAM1	RYK	P34925	711
DAAM1	PTBP2	Q9UKA9	684
DAAM1	ADAR	P55265	675
DAAM1	PFN4	Q8NHR9	657
DAAM1	VANGL1	Q8TAA9	653
DAAM1	PTK7	Q13308	645
DAAM1	VANGL2	Q9ULK5	614

IntAct

106 interactions, top by confidence:

A	B	Type	Score
RHOA	ARHGEF11	psi-mi:“MI:0914”(association)	0.900
DAAM1	RHOA	psi-mi:“MI:0407”(direct interaction)	0.870
DAAM1	RHOA	psi-mi:“MI:0915”(physical association)	0.870
DAAM1	RHOA	psi-mi:“MI:2364”(proximity)	0.870
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
RHOC	RAP1GDS1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DAAM1	RHOC	psi-mi:“MI:0407”(direct interaction)	0.690
RHOD	DAAM1	psi-mi:“MI:0407”(direct interaction)	0.690
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
DAAM1	DAAM1	psi-mi:“MI:0407”(direct interaction)	0.610
DAAM1	DAAM1	psi-mi:“MI:0915”(physical association)	0.610
RHOA	DIAPH1	psi-mi:“MI:0914”(association)	0.600
DAAM1	SRC	psi-mi:“MI:0915”(physical association)	0.560
SRC	DAAM1	psi-mi:“MI:0403”(colocalization)	0.560
CBX5	KPNA3	psi-mi:“MI:0914”(association)	0.530
GPN3	POLR3A	psi-mi:“MI:0914”(association)	0.530

BioGRID (91): DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Co-localization), DAAM1 (Proximity Label-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A6H7I5, B0DOB5, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EGS5, H2KZZ6, O95466, P21575, P23678, P27619, P39052, P39053, P39054, P39055, P48608, P50570, P78344, P79398, Q01968, Q05193, Q08877, Q08DF4, Q15057, Q15172, Q24564, Q2KI89, Q5R629, Q5R7J9, Q5ZK62, Q62448, Q6IVG4, Q6NXC0, Q6ZQK5, Q7SIG6, Q7XPJ0, Q80U19, Q86T65

Diamond homologs: A0A1D5P556, A4D2P6, B0DOB5, O08808, O23373, O60610, O70566, Q6MWG9, Q80U19, Q86T65, Q8BPM0, Q9FJX6, Q9Y4D1, O22824, Q5TJ56, Q8S0F0, A0A3Q1LSX9, A2XUA1, A2YVG8, A3AB67, F1LVW7, O04532, O48682, P0C5K5, Q0D519, Q0D5P3, Q0DLG0, Q10Q99, Q24120, Q54PI9, Q69MT2, Q6H7U3, Q6NXC0, Q6ZKB2, Q6ZPF4, Q7XUV2, Q7XWS7, Q84ZL0, Q8GX37, Q8H8K7

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
DAAM1	“up-regulates activity”	RHOA	binding
DVL1	“up-regulates activity”	DAAM1	binding
DAAM1	“up-regulates activity”	RAC1
DVL1P1	up-regulates	DAAM1	binding
SRC	“up-regulates activity”	DAAM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Sema4D induced cell migration and growth-cone collapse	5	37.1×	9e-05
RHO GTPases Activate Formins	9	9.1×	1e-04
Clathrin-mediated endocytosis	7	7.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
Rho protein signal transduction	5	12.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	112
Likely benign	9
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57783	GRCh38/hg38 14q23.1(chr14:58680457-59394168)x1	Pathogenic

SpliceAI

3710 predictions. Top by Δscore:

Variant	Effect	Δscore
14:59263658:GTG:G	donor_gain	1.0000
14:59291213:TCAG:T	acceptor_loss	1.0000
14:59291214:CAGG:C	acceptor_loss	1.0000
14:59291215:A:AC	acceptor_loss	1.0000
14:59291215:A:AG	acceptor_gain	1.0000
14:59291215:AG:A	acceptor_gain	1.0000
14:59291215:AGGAT:A	acceptor_gain	1.0000
14:59291216:G:GG	acceptor_gain	1.0000
14:59291216:GG:G	acceptor_gain	1.0000
14:59291216:GGA:G	acceptor_gain	1.0000
14:59291216:GGAT:G	acceptor_gain	1.0000
14:59291216:GGATG:G	acceptor_gain	1.0000
14:59291304:AAGGT:A	donor_loss	1.0000
14:59291305:AGGT:A	donor_loss	1.0000
14:59291306:GGTA:G	donor_loss	1.0000
14:59291307:G:GG	donor_gain	1.0000
14:59291307:GTAAG:G	donor_loss	1.0000
14:59291308:T:G	donor_loss	1.0000
14:59315347:CTGCT:C	donor_gain	1.0000
14:59315348:TGCT:T	donor_gain	1.0000
14:59315349:GCT:G	donor_gain	1.0000
14:59315349:GCTG:G	donor_gain	1.0000
14:59315350:CT:C	donor_gain	1.0000
14:59315351:TGT:T	donor_loss	1.0000
14:59315352:G:GA	donor_loss	1.0000
14:59315352:G:GG	donor_gain	1.0000
14:59315353:TAAGT:T	donor_loss	1.0000
14:59315354:AAGTA:A	donor_loss	1.0000
14:59320485:CATA:C	acceptor_loss	1.0000
14:59320486:A:AG	acceptor_gain	1.0000

AlphaMissense

7128 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:59291224:T:C	L64P	1.000
14:59291230:T:C	L66P	1.000
14:59320562:G:C	A140P	1.000
14:59320566:T:A	L141Q	1.000
14:59320566:T:C	L141P	1.000
14:59322893:T:C	F148L	1.000
14:59322895:T:A	F148L	1.000
14:59322895:T:G	F148L	1.000
14:59323021:C:A	N190K	1.000
14:59323021:C:G	N190K	1.000
14:59323031:G:C	G194R	1.000
14:59323032:G:A	G194D	1.000
14:59324376:T:C	L304P	1.000
14:59324379:G:C	R305P	1.000
14:59325690:G:C	R339P	1.000
14:59325698:G:C	D342H	1.000
14:59326539:T:A	W402R	1.000
14:59326539:T:C	W402R	1.000
14:59326973:G:C	A452P	1.000
14:59331479:A:G	K611E	1.000
14:59331481:A:C	K611N	1.000
14:59331481:A:T	K611N	1.000
14:59331491:T:A	W615R	1.000
14:59331491:T:C	W615R	1.000
14:59331834:T:A	W628R	1.000
14:59331834:T:C	W628R	1.000
14:59340152:G:C	A693P	1.000
14:59340157:G:C	Q694H	1.000
14:59340157:G:T	Q694H	1.000
14:59340158:A:G	N695D	1.000

dbSNP variants (sampled 300 via entrez): RS1000001867 (14:59191559 C>A), RS1000008552 (14:59319619 G>A), RS1000017860 (14:59349848 G>A), RS1000023234 (14:59228913 G>A,C), RS1000078870 (14:59342196 G>A,C), RS1000099398 (14:59299922 A>G), RS1000108959 (14:59297864 C>T), RS1000114258 (14:59251304 A>G), RS1000126438 (14:59355589 G>A), RS1000128032 (14:59189196 G>T), RS1000155494 (14:59246574 A>C,G), RS1000161911 (14:59295233 G>A), RS1000177488 (14:59358372 CAACT>C), RS1000203499 (14:59247588 C>A), RS1000262650 (14:59273630 T>A)

Disease associations

OMIM: gene MIM:606626 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002718_6	Type 2 diabetes	5.000000e-06
GCST006153_3	Parkinsonism in frontotemporal lobe dementia	9.000000e-06
GCST008703_1	Occipital lobe volume	7.000000e-09
GCST008707_4	Occipital lobe volume	3.000000e-09
GCST008710_2	Parietal lobe volume	2.000000e-06
GCST009185_7	Inferior temporal gyrus volume	2.000000e-06
GCST009462_13	Optic disc size	2.000000e-12
GCST009462_77	Optic disc size	2.000000e-14
GCST010225_24	Cortical surface area (visual PC2)	4.000000e-14
GCST010225_29	Cortical surface area (visual PC2)	9.000000e-10
GCST010397_77	Gut microbiota (bacterial taxa, rank normal transformation method)	6.000000e-06
GCST010703_89	Brain morphology (MOSTest)	1.000000e-76
GCST011616_23	Cortical volume	5.000000e-10
GCST011616_35	Cortical volume	4.000000e-20
GCST011616_41	Cortical volume	5.000000e-20
GCST011616_45	Cortical volume	7.000000e-16
GCST011616_46	Cortical volume	1.000000e-20
GCST011616_48	Cortical volume	5.000000e-43
GCST011616_51	Cortical volume	1.000000e-29
GCST011617_2	Cortical surface area	5.000000e-40
GCST011617_21	Cortical surface area	3.000000e-26
GCST011617_28	Cortical surface area	2.000000e-38
GCST011617_30	Cortical surface area	3.000000e-43
GCST011617_32	Cortical surface area	3.000000e-41
GCST011617_6	Cortical surface area	1.000000e-30
GCST011618_10	Cortical thickness	3.000000e-23
GCST90010427_17	Left–right brain asymmetry	4.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004771	visual cortical surface area measurement
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
trichostatin A	affects expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
chromium hexavalent ion	decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
K 7174	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
abrine	increases expression	1
ON 01910	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
pyrachlostrobin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7NB	Ubigene A-549 DAAM1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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