DNMBP

Summary

DNMBP (dynamin binding protein, HGNC:30373) is a protein-coding gene on chromosome 10q24.2, encoding Dynamin-binding protein (Q6XZF7). Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton.

This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer’s disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23268 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 48 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 300 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• MANE Select transcript: NM_015221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30373
Approved symbol	DNMBP
Name	dynamin binding protein
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1010, Tuba, ARHGEF36
Ensembl gene	ENSG00000107554
Ensembl biotype	protein_coding
OMIM	611282
Entrez	23268

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000324109, ENST00000472036, ENST00000543621, ENST00000636706, ENST00000856964, ENST00000856965, ENST00000928782

RefSeq mRNA: 3 — MANE Select: NM_015221 NM_001318326, NM_001318327, NM_015221

CCDS: CCDS7485, CCDS81494, CCDS81495

Canonical transcript exons

ENST00000324109 — 17 exons

Exon	Start	End
ENSE00001121895	99899919	99900066
ENSE00001121904	99907995	99908094
ENSE00001424407	100009838	100009947
ENSE00002441919	99886300	99886632
ENSE00002454076	99875577	99877336
ENSE00002462902	99955214	99957205
ENSE00002467832	99896267	99896397
ENSE00002469131	99879811	99880361
ENSE00002488566	99898743	99898760
ENSE00002496027	99969115	99969237
ENSE00002496644	99885687	99885866
ENSE00002515360	99884011	99884209
ENSE00002702159	99898086	99898285
ENSE00002715298	99971980	99972134
ENSE00003599614	99894946	99895050
ENSE00003622745	99888825	99888953
ENSE00003688318	99908953	99909146

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 93.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3879 / max 272.6198, expressed in 1689 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111009	11.0278	1676
110997	0.9112	159
111000	0.8913	191
110998	0.4116	142
111004	0.0311	5
111005	0.0275	4
110999	0.0269	11
111003	0.0247	4
111006	0.0167	4
111002	0.0104	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	93.69	gold quality
ileal mucosa	UBERON:0000331	92.81	gold quality
colonic mucosa	UBERON:0000317	91.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.03	gold quality
ventricular zone	UBERON:0003053	90.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.24	gold quality
stromal cell of endometrium	CL:0002255	89.57	gold quality
epithelium of bronchus	UBERON:0002031	89.28	gold quality
jejunum	UBERON:0002115	89.03	gold quality
bronchial epithelial cell	CL:0002328	88.98	gold quality
skin of leg	UBERON:0001511	88.96	gold quality
duodenum	UBERON:0002114	88.93	gold quality
skin of abdomen	UBERON:0001416	88.88	gold quality
bronchus	UBERON:0002185	88.87	gold quality
upper arm skin	UBERON:0004263	88.71	gold quality
zone of skin	UBERON:0000014	88.52	gold quality
rectum	UBERON:0001052	88.49	gold quality
thymus	UBERON:0002370	88.16	gold quality
seminal vesicle	UBERON:0000998	88.11	gold quality
renal medulla	UBERON:0000362	87.99	gold quality
mucosa of transverse colon	UBERON:0004991	87.99	gold quality
cardia of stomach	UBERON:0001162	87.96	gold quality
upper leg skin	UBERON:0004262	87.84	gold quality
type B pancreatic cell	CL:0000169	87.63	gold quality
mucosa of urinary bladder	UBERON:0001259	87.60	gold quality
oviduct epithelium	UBERON:0004804	87.56	gold quality
body of stomach	UBERON:0001161	87.30	gold quality
olfactory bulb	UBERON:0002264	87.14	gold quality
colonic epithelium	UBERON:0000397	87.07	gold quality
urinary bladder	UBERON:0001255	87.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting DNMBP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-204-5P	99.79	71.62	2439

Literature-anchored findings (GeneRIF, showing 11)

• functions to bring together dynamin with actin regulatory proteins (PMID:14506234)
• Results confirmed DNMBP may be one of the susceptibility genes for Alzheimer’s disease. (PMID:16740596)
• Tuba controls the shaping of cell junctions through the local activation of Cdc42 and its effectors. (PMID:17015620)
• We observed no association of statistical significance in either the total sample or the APOE*4 non-carriers for any of the SNPs of Dynamin Binding Protein. (PMID:17442457)
• findings underscore a role for DNMBP in the genetic risk for late-onset Alzheimer’s disease in the Belgian population (PMID:18359537)
• Although DNMBP is an excellent candidate gene because of its role in the APP recycling pathways and being located within a chromosome 10 linkage region, we are unable to confirm that DNMBP is associated with LOAD (PMID:18452187)
• Polyproline region of N-WASP is required for the localization of Tuba at the pre-apical patch. (PMID:21677511)
• Cdc42 and its specific guanine nucleotide-exchange factor (GEF), Tuba, localize to linear invadosomes, and both are required for linear invadosome formation (PMID:25422375)
• The rs3740058 in DNMBP was significantly differently in genotype between Alaheimer diease and control in APOE epsilon4epsilon4 subgroup, but showed no effect on Alzheimer disease risk, either did rs11190305 polymorphisms in DNMBP. (PMID:25801238)
• DNMBP loss-of-function variants cause infantile-onset cataracts in humans. (PMID:30290152)
• Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/alpha-tubulin acetylation. (PMID:31878840)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnmbp	ENSDARG00000074121
mus_musculus	Dnmbp	ENSMUSG00000025195
rattus_norvegicus	Dnmbp	ENSRNOG00000050742
caenorhabditis_elegans		WBGENE00044989

Paralogs (2): ARHGEF37 (ENSG00000183111), ARHGEF38 (ENSG00000236699)

Protein

Protein identifiers

Dynamin-binding protein — Q6XZF7 (reviewed: Q6XZF7)

Alternative names: Scaffold protein Tuba

All UniProt accessions (3): Q6XZF7, A0A1B0GTX1, A0A1C7CYY6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells. Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation. Plays a role in ciliogenesis. May play a role in membrane trafficking between the cell surface and the Golgi.

Subunit / interactions. Binds DNM1 via its N-terminal SH3 domains. The C-terminal SH3 domain binds a complex containing actin, tubulin, Hsp70 and actin-regulatory proteins, such as ENAH, EVL, WIRE, CR16, WAVE1 and NAP1L1. Interacts with FASLG. Interacts (via SH3 domain 6) with WASL. Interacts (via SH3 domain 6) interacts with ENAH. Interacts (via C-terminal domain) with TJP1; required for the apical cell-cell junction localization of DNMBP. (Microbial infection) Interacts (via SH3 domain 6) with L.monocytogenes InlC.

Subcellular location. Cytoplasm. Golgi apparatus. Golgi stack. Cytoskeleton. Synapse. Cell junction.

Tissue specificity. Detected in heart, brain, lung, liver, skeletal muscle, kidney and pancreas.

Disease relevance. Cataract 48 (CTRCT48) [MIM:618415] A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT48 is an autosomal recessive form characterized by infantile or early-childhood onset. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6XZF7-1	1	yes
Q6XZF7-2	2

RefSeq proteins (3): NP_001305255, NP_001305256, NP_056036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001452	SH3_domain	Domain
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035817	DNMBP_SH3_N1	Domain
IPR035818	DNMBP_SH3_N2	Domain
IPR035819	DNMBP_SH3_N3	Domain
IPR035820	DNMBP_SH3_C1	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051492	Dynamin-Rho_GEF	Family

Pfam: PF00018, PF00621, PF03114, PF07653, PF14604

UniProt features (56 total): strand 17, domain 8, region of interest 5, compositionally biased region 5, sequence variant 5, helix 5, modified residue 3, mutagenesis site 3, coiled-coil region 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4CC2	X-RAY DIFFRACTION	1.55
4GLM	X-RAY DIFFRACTION	1.9
4CC3	X-RAY DIFFRACTION	1.97
4CC7	X-RAY DIFFRACTION	1.97
4CC4	X-RAY DIFFRACTION	2.6
1UG1	SOLUTION NMR
1UHC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XZF7-F1	64.91	0.28

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): 1, 496, 684

Mutagenesis-validated functional residues (3):

Position	Phenotype
1521	decreased interaction of sh3 domain 6 with l.monocytogenes inlc.
1529	wild-type interaction of sh3 domain 6 with l.monocytogenes inlc.
1569	decreased interaction of sh3 domain 6 with l.monocytogenes inlc.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle

MSigDB gene sets: 201 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_CILIUM_ORGANIZATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_ORGANELLE_ASSEMBLY, BROWNE_HCMV_INFECTION_24HR_DN, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_CELL_CELL_JUNCTION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_SHAPE, GOCC_GOLGI_STACK, GOCC_SYNAPSE, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, LEE_DOUBLE_POLAR_THYMOCYTE

GO Biological Process (4): regulation of cell shape (GO:0008360), intracellular signal transduction (GO:0035556), regulation of small GTPase mediated signal transduction (GO:0051056), cilium assembly (GO:0060271)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), cytosol (GO:0005829), cytoskeleton (GO:0005856), cell-cell junction (GO:0005911), nuclear body (GO:0016604), synapse (GO:0045202), presynapse (GO:0098793), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
intracellular anatomical structure	2
nuclear lumen	2
cytoplasm	2
cell junction	2
regulation of cell morphogenesis	1
regulation of biological quality	1
signal transduction	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
anchoring junction	1
nucleoplasm	1
synapse	1

Protein interactions and networks

STRING

1122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNMBP	WASL	O00401	873
DNMBP	BIN1	O00499	815
DNMBP	DNM1	Q05193	553
DNMBP	WIPF2	Q8TF74	550
DNMBP	AMPH	P49418	498
DNMBP	MARVELD2	Q8N4S9	497
DNMBP	VASP	P50552	492
DNMBP	C2CD4A	Q8NCU7	485
DNMBP	ZNF768	Q9H5H4	473
DNMBP	FCHSD1	Q86WN1	464
DNMBP	ARHGAP44	Q17R89	446
DNMBP	ENAH	Q8N8S7	446
DNMBP	RAPGEF1	Q13905	418
DNMBP	RRS1	Q15050	418
DNMBP	SCAPER	Q9BY12	416

IntAct

68 interactions, top by confidence:

A	B	Type	Score
DNMBP	BIN3	psi-mi:“MI:0915”(physical association)	0.790
BIN3	DNMBP	psi-mi:“MI:0915”(physical association)	0.790
DNM2	DNM1	psi-mi:“MI:0914”(association)	0.740
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
BIN3	ARHGEF37	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
DNMBP	FASLG	psi-mi:“MI:0407”(direct interaction)	0.440
Dnm1	DNMBP	psi-mi:“MI:0915”(physical association)	0.400
Nedd1		psi-mi:“MI:0914”(association)	0.350
Cd2ap		psi-mi:“MI:0914”(association)	0.350
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CAMK2D	DVL2	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DNM3	SNX2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): DNMBP (Affinity Capture-MS), DNMBP (Affinity Capture-MS), DNMBP (Proximity Label-MS), DNMBP (Proximity Label-MS), DNMBP (Proximity Label-MS), DNMBP (Affinity Capture-MS), DNMBP (Affinity Capture-MS), DNMBP (Affinity Capture-MS), DNMBP (Affinity Capture-MS), DNM1 (Affinity Capture-Western), DNM1 (Reconstituted Complex), CYFIP2 (Affinity Capture-MS), WASF1 (Affinity Capture-MS), HSPA4 (Affinity Capture-MS), WASL (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JUG7, A1L390, A2AHC3, B2RWW0, O14924, O43182, O54834, O54960, O94885, P59808, P80192, P97434, Q13009, Q17R10, Q3U1V8, Q3U214, Q4VAC9, Q5DTU0, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q60610, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6P720, Q6P9R4, Q6WCQ1, Q6XZF7, Q76G19, Q76LL6, Q7T2V3, Q80Z38, Q810W7, Q8IX03, Q8N103, Q8R0S2, Q8R4H2

Diamond homologs: A1CEK6, A1DFN5, A1DFP5, A2QW93, A2QWA2, A3LXQ8, A4FU49, A4RF61, A6QLK6, B0BNA1, F4KAU9, O08641, O14964, O35179, O35180, O35413, O35964, O43125, O74749, O80910, O94875, P07751, P0CR78, P0CR79, P10569, P19878, P29355, P38753, P62993, P62994, P87379, Q06449, Q07883, Q08012, Q0CJU8, Q0CJV3, Q0U4Z8, Q0U6X7, Q0V8S0, Q15080

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DNMBP	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
Activation of BAD and translocation to mitochondria	6	86.2×	8e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	76.0×	9e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	76.0×	9e-09
Activation of BH3-only proteins	6	56.2×	6e-08
RHO GTPases activate PKNs	6	35.9×	8e-07
Intrinsic Pathway for Apoptosis	6	33.1×	1e-06
G2/M Checkpoints	8	20.3×	3e-07
SARS-CoV-1-host interactions	6	19.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	10	13.0×	3e-06
intracellular protein localization	8	11.5×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	216
Likely benign	32
Benign	32

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4277807	NM_015221.4(DNMBP):c.2260+1G>A	Pathogenic
626917	NM_015221.4(DNMBP):c.811C>T (p.Arg271Ter)	Pathogenic
626918	NM_015221.4(DNMBP):c.2947_2948del (p.Glu982_Asp983insTer)	Pathogenic
626919	NM_015221.4(DNMBP):c.2852_2855del (p.Thr951fs)	Pathogenic
3148840	NM_015221.4(DNMBP):c.1442del (p.Gly481fs)	Likely pathogenic

SpliceAI

4020 predictions. Top by Δscore:

Variant	Effect	Δscore
10:100002940:A:AC	donor_gain	1.0000
10:100002941:C:CC	donor_gain	1.0000
10:100002941:CT:C	donor_gain	1.0000
10:99880359:TGA:T	acceptor_gain	1.0000
10:99880362:C:CC	acceptor_gain	1.0000
10:99884005:TCTTA:T	donor_loss	1.0000
10:99884006:CTTA:C	donor_loss	1.0000
10:99884007:TTAC:T	donor_loss	1.0000
10:99884008:TACCT:T	donor_loss	1.0000
10:99884205:CTTGG:C	acceptor_gain	1.0000
10:99884206:TTGG:T	acceptor_gain	1.0000
10:99884208:GGCTG:G	acceptor_loss	1.0000
10:99885681:ACT:A	donor_loss	1.0000
10:99885683:T:TA	donor_loss	1.0000
10:99885684:CACCA:C	donor_loss	1.0000
10:99885686:CCAGG:C	donor_gain	1.0000
10:99885864:TAA:T	acceptor_gain	1.0000
10:99885867:C:CC	acceptor_gain	1.0000
10:99885874:CCA:C	acceptor_gain	1.0000
10:99885875:C:CT	acceptor_gain	1.0000
10:99885875:C:T	acceptor_gain	1.0000
10:99885876:A:C	acceptor_gain	1.0000
10:99885876:A:T	acceptor_gain	1.0000
10:99885886:C:CT	acceptor_gain	1.0000
10:99885887:A:T	acceptor_gain	1.0000
10:99885891:A:AC	acceptor_gain	1.0000
10:99885891:A:C	acceptor_gain	1.0000
10:99886294:ACTC:A	donor_loss	1.0000
10:99886296:TCAC:T	donor_loss	1.0000
10:99886297:CA:C	donor_loss	1.0000

AlphaMissense

10329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:99877188:A:T	V1566D	1.000
10:99886415:A:G	L1168P	1.000
10:99886427:A:G	L1164P	1.000
10:99886439:A:G	L1160P	1.000
10:99886547:C:G	R1124P	1.000
10:99898097:C:G	R970P	1.000
10:99898100:C:G	R969P	1.000
10:99877225:A:G	W1554R	0.999
10:99877225:A:T	W1554R	0.999
10:99886427:A:T	L1164Q	0.999
10:99886443:C:G	A1159P	0.999
10:99886535:A:G	L1128P	0.999
10:99886537:C:A	K1127N	0.999
10:99886537:C:G	K1127N	0.999
10:99886539:T:C	K1127E	0.999
10:99886548:G:T	R1124S	0.999
10:99886549:T:A	K1123N	0.999
10:99886549:T:G	K1123N	0.999
10:99886550:T:A	K1123I	0.999
10:99886551:T:C	K1123E	0.999
10:99886559:A:G	L1120P	0.999
10:99886610:A:T	V1103D	0.999
10:99896310:C:G	R1003P	0.999
10:99896320:T:C	K1000E	0.999
10:99896321:C:A	K999N	0.999
10:99896321:C:G	K999N	0.999
10:99896323:T:C	K999E	0.999
10:99896328:A:T	I997N	0.999
10:99896332:A:G	S996P	0.999
10:99896343:A:G	L992P	0.999

dbSNP variants (sampled 300 via entrez): RS1000024628 (10:99881121 A>G), RS1000034119 (10:99996777 C>G), RS1000040931 (10:99984972 G>A,T), RS1000047196 (10:99896227 T>C), RS1000095192 (10:99924730 T>C), RS1000109305 (10:99983332 G>A), RS1000120424 (10:99946892 C>G), RS1000151314 (10:99976926 C>T), RS1000160199 (10:99990652 T>G), RS1000188027 (10:99945396 G>A), RS1000198074 (10:99928457 C>G,T), RS1000218960 (10:99978626 T>C), RS1000221936 (10:99989825 C>T), RS1000236291 (10:99983186 C>A,T), RS1000245955 (10:99983427 G>A,C)

Disease associations

OMIM: gene MIM:611282 | disease phenotypes: MIM:618415, MIM:236600

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 48	Strong	Autosomal recessive
total early-onset cataract	Supportive	Autosomal dominant

Mondo (3): cataract 48 (MONDO:0032735), hydrocephalus, nonsyndromic, autosomal recessive 1 (MONDO:0009360), total early-onset cataract (MONDO:0021548)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000518	Cataract
HP:0000577	Exotropia
HP:0000616	Miosis
HP:0000646	Amblyopia
HP:0003577	Congenital onset
HP:0007663	Reduced visual acuity
HP:0012043	Pendular nystagmus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010484_6	Stent thrombosis in response to clopidogrel treatment	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006919	cardiovascular event measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295871 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression	5
sodium arsenite	decreases stability, decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation	2
FR900359	affects phosphorylation	1
urushiol	decreases expression	1
chloroacetaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
ormosil	increases expression, affects binding	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118663	Binding	Binding affinity to DNMBP in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study