DBNL

Summary

DBNL (drebrin like, HGNC:2696) is a protein-coding gene on chromosome 7p13, encoding Drebrin-like protein (Q9UJU6). Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis.

Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm; intracellular membrane-bounded organelle; and plasma membrane.

Source: NCBI Gene 28988 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 273 total — 6 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001014436

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2696
Approved symbol	DBNL
Name	drebrin like
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	SH3P7, HIP-55, ABP1
Ensembl gene	ENSG00000136279
Ensembl biotype	protein_coding
OMIM	610106
Entrez	28988

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 33 protein_coding, 9 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000411855, ENST00000423561, ENST00000429716, ENST00000432854, ENST00000439815, ENST00000439983, ENST00000440166, ENST00000441840, ENST00000441904, ENST00000448521, ENST00000449997, ENST00000452661, ENST00000452943, ENST00000456905, ENST00000458579, ENST00000464762, ENST00000468694, ENST00000485932, ENST00000490734, ENST00000494774, ENST00000497184, ENST00000498733, ENST00000864278, ENST00000864279, ENST00000864280, ENST00000864281, ENST00000864282, ENST00000864283, ENST00000864284, ENST00000864285, ENST00000864286, ENST00000864287, ENST00000864288, ENST00000914504, ENST00000914505, ENST00000914506, ENST00000967642, ENST00000967643, ENST00000967644, ENST00000967645, ENST00000967646, ENST00000967647, ENST00000967648, ENST00000967649, ENST00000967650, ENST00000967651

RefSeq mRNA: 6 — MANE Select: NM_001014436 NM_001014436, NM_001122956, NM_001284313, NM_001284315, NM_001362723, NM_014063

CCDS: CCDS34622, CCDS34623, CCDS47579, CCDS64633, CCDS64634

Canonical transcript exons

ENST00000448521 — 13 exons

Exon	Start	End
ENSE00001711542	44060777	44069456
ENSE00002231147	44044702	44044820
ENSE00003479155	44051830	44051942
ENSE00003517478	44060048	44060153
ENSE00003547243	44057782	44057859
ENSE00003549397	44052867	44052941
ENSE00003556614	44058129	44058280
ENSE00003566381	44056757	44056903
ENSE00003590231	44059543	44059658
ENSE00003618909	44058902	44058983
ENSE00003624256	44058432	44058480
ENSE00003631502	44050225	44050280
ENSE00003690391	44059354	44059449

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.9890 / max 580.1176, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78384	50.8413	1825
78383	1.1477	836

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.92	gold quality
monocyte	CL:0000576	98.63	gold quality
leukocyte	CL:0000738	98.57	gold quality
granulocyte	CL:0000094	98.13	gold quality
esophagus mucosa	UBERON:0002469	98.02	gold quality
vermiform appendix	UBERON:0001154	97.60	gold quality
spleen	UBERON:0002106	96.98	gold quality
esophagus	UBERON:0001043	96.93	gold quality
mucosa of transverse colon	UBERON:0004991	96.72	gold quality
stromal cell of endometrium	CL:0002255	96.54	gold quality
gall bladder	UBERON:0002110	96.28	gold quality
left coronary artery	UBERON:0001626	96.15	gold quality
ectocervix	UBERON:0012249	96.14	gold quality
right coronary artery	UBERON:0001625	96.03	gold quality
thoracic aorta	UBERON:0001515	95.89	gold quality
ascending aorta	UBERON:0001496	95.88	gold quality
lower esophagus	UBERON:0013473	95.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.78	gold quality
coronary artery	UBERON:0001621	95.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.76	gold quality
descending thoracic aorta	UBERON:0002345	95.66	gold quality
lymph node	UBERON:0000029	95.57	gold quality
upper lobe of left lung	UBERON:0008952	95.54	gold quality
caecum	UBERON:0001153	95.48	gold quality
aorta	UBERON:0000947	95.47	gold quality
left uterine tube	UBERON:0001303	95.33	gold quality
apex of heart	UBERON:0002098	95.31	gold quality
popliteal artery	UBERON:0002250	95.27	gold quality
tibial artery	UBERON:0007610	95.26	gold quality
pancreatic ductal cell	CL:0002079	95.09	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	790.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting DBNL, 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-10401-5P	99.99	65.79	948
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-346	97.01	66.97	662
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 15)

• substrate for caspase cleavage during apoptosis (PMID:11689006)
• SH3P7 is essential for endocytosis but not lamellipodia formation. (PMID:12565838)
• HIP-55 plays a functional role in TCR signaling (PMID:14557276)
• HIP-55 is a key novel component of the immunological synapse that modulates T cell activation by connecting actin cytoskeleton and TCRs to gene activation and endocytic processes (PMID:14729663)
• HIP-55 has roles in T-cell proliferation, cytokine production, and immune responses (PMID:16055701)
• unexpected role of 3BP2 in endocytic and cytoskeletal regulation through its interaction with CIN85 and HIP-55 (PMID:17306257)
• Filamentous actin (F-actin)-binding protein 1 (Abp1/SH3P7/HIP-55) has a profound impact on synaptic organization by making a required functional connection between postsynaptic density components and postsynaptic actin dynamics. (PMID:18829961)
• mAbp1 is of fundamental importance for spreading and migration under shear stress conditions, which are critical prerequisites for efficient PMN extravasation during inflammation. (PMID:22450813)
• Data indicate that fourteen phosphorylation sites along the primary structure of hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa (HIP-55) rotein were identified. (PMID:24651461)
• Data suggest that HIP-55 could play an important role in the growth and cellular proliferation and HIP-55 dysfunction could be involved in tumorigenesis. (PMID:24668193)
• HIP-55 expression promoted proliferation, colony formation, migration, and invasion of lung cancer cells and was upregulated in lung cancer cell lines and tumor tissues of lung cancer patients (PMID:24912570)
• Data suggest that by binding to both clathrin and F-actin, mammalian actin-binding protein 1 (mAbp1; HIP-55 or SH3P7) is specifically recruited at a late stage of clathrin-coated pits (CCPs) formation, which subsequently recruits dynamin to CCPs. (PMID:25690657)
• The results presented here indicate that targeting IL-1alpha with subcutaneous MABp1 adminisration has a strong potential therapeutic value in treating psoriasis and may provide a novel future treatment of this often devastating disease. (PMID:25715176)
• findings show that mAbp1 and FHL2 are novel binding partners that differentially regulate Rho GTPase signaling and MTLn3 breast cancer cell invasion (PMID:27129278)
• Dimerization of Human Drebrin-like Protein Governs Its Biological Activity. (PMID:32282191)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dbnla	ENSDARG00000008170
danio_rerio	dbnlb	ENSDARG00000016016
mus_musculus	Dbnl	ENSMUSG00000020476
rattus_norvegicus	Dbnl	ENSRNOG00000012378

Paralogs (4): CTTN (ENSG00000085733), COTL1 (ENSG00000103187), DBN1 (ENSG00000113758), HCLS1 (ENSG00000180353)

Protein

Protein identifiers

Drebrin-like protein — Q9UJU6 (reviewed: Q9UJU6)

Alternative names: Cervical SH3P7, Cervical mucin-associated protein, Drebrin-F, HPK1-interacting protein of 55 kDa, SH3 domain-containing protein 7

All UniProt accessions (12): B4DDD6, Q9UJU6, F2Z2V3, F2Z3E3, F8WB73, F8WBB2, F8WBG8, F8WC20, F8WCK3, F8WFE1, H0Y5J4, H7C111

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes. May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes.

Subunit / interactions. Interacts with SHANK2, SHANK3 and SYN1. Interacts with FGD1 and DNM1. Interacts with ANKRD54. Interacts with COBL. Interacts with WASL and WIPF1. Interacts with MAP4K1 and PRAM1.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Ruffle. Cell cortex. Cytosol. Synapse. Perikaryon. Neuron projection. Cell membrane. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Golgi apparatus membrane. Podosome. Early endosome. Dendrite. Postsynaptic density.

Post-translational modifications. Degraded by caspases during apoptosis.

Domain organisation. The SH3 domain mediates interaction with SHANK2, SHANK3 and PRAM1.

Similarity. Belongs to the ABP1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UJU6-1	1	yes
Q9UJU6-2	2
Q9UJU6-3	3
Q9UJU6-4	4
Q9UJU6-5	5
Q9UJU6-6	6

RefSeq proteins (6): NP_001014436, NP_001116428, NP_001271242, NP_001271244, NP_001349652, NP_054782 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR002108	ADF-H	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR035717	Drebrin-like_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF00241, PF14604

UniProt features (48 total): modified residue 16, strand 7, splice variant 5, helix 5, sequence conflict 4, compositionally biased region 3, domain 2, chain 1, mutagenesis site 1, region of interest 1, coiled-coil region 1, turn 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X67	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJU6-F1	74.60	0.47

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 (1): 361–362 (cleavage; by caspase-3)

Post-translational modifications (16): 160, 176, 232, 269, 272, 275, 283, 288, 291, 334, 344, 232, 232, 137, 183, 26

Mutagenesis-validated functional residues (1):

Position	Phenotype
361	abolishes cleavage by caspase-3.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-264870	Caspase-mediated cleavage of cytoskeletal proteins
R-HSA-6794361	Neurexins and neuroligins
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 198 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, TSENG_IRS1_TARGETS_UP, GOBP_SYNAPSE_ASSEMBLY, GOCC_SECRETORY_GRANULE, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, GOBP_CELL_JUNCTION_ORGANIZATION, GOCC_COATED_VESICLE, GOBP_ORGANELLE_ASSEMBLY, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GCM_DDX11

GO Biological Process (9): adaptive immune response (GO:0002250), endocytosis (GO:0006897), synapse assembly (GO:0007416), Rac protein signal transduction (GO:0016601), neuron projection morphogenesis (GO:0048812), membrane organization (GO:0061024), podosome assembly (GO:0071800), immune system process (GO:0002376), postsynaptic actin cytoskeleton organization (GO:0098974)

GO Molecular Function (7): actin binding (GO:0003779), enzyme activator activity (GO:0008047), protein domain specific binding (GO:0019904), cadherin binding (GO:0045296), actin filament binding (GO:0051015), structural constituent of postsynaptic actin cytoskeleton (GO:0098973), protein binding (GO:0005515)

GO Cellular Component (31): Golgi membrane (GO:0000139), ruffle (GO:0001726), podosome (GO:0002102), extracellular region (GO:0005576), cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), postsynaptic density (GO:0014069), membrane (GO:0016020), lamellipodium (GO:0030027), dendrite (GO:0030425), clathrin-coated vesicle membrane (GO:0030665), secretory granule lumen (GO:0034774), perikaryon (GO:0043204), extracellular exosome (GO:0070062), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), anchoring junction (GO:0070161), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Apoptotic cleavage of cellular proteins	1
Protein-protein interactions at synapses	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cell leading edge	2
plasma membrane bounded cell projection	2
cytoplasm	2
cell periphery	2
synapse	2
immune response	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
nervous system development	1
cell junction assembly	1
synapse organization	1
small GTPase-mediated signal transduction	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
cellular component organization	1
protein-containing complex assembly	1
plasma membrane bounded cell projection assembly	1
biological_process	1
actin cytoskeleton organization	1
postsynaptic cytoskeleton organization	1
cytoskeletal protein binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
protein binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
structural constituent of cytoskeleton	1
postsynaptic actin cytoskeleton	1
postsynaptic actin cytoskeleton organization	1
structural constituent of postsynapse	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
actin-based cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

124 interactions, top by confidence:

A	B	Type	Score
SH2D4A	DBNL	psi-mi:“MI:0915”(physical association)	0.760
DBNL	SH2D4A	psi-mi:“MI:0915”(physical association)	0.760
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DBNL	HERC2	psi-mi:“MI:0914”(association)	0.670
SH3BP2	DBNL	psi-mi:“MI:0915”(physical association)	0.660
DBNL	SH3BP2	psi-mi:“MI:0915”(physical association)	0.660
DBNL	SH3BP2	psi-mi:“MI:0403”(colocalization)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
DBNL	SH2D4A	psi-mi:“MI:0915”(physical association)	0.560
SH2D4A	DBNL	psi-mi:“MI:0915”(physical association)	0.560
DBNL	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	DBNL	psi-mi:“MI:0915”(physical association)	0.560
DBNL	GSN	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	DBNL	psi-mi:“MI:0915”(physical association)	0.560
BAG6	DBNL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (223): SH2D4A (Two-hybrid), DBNL (Affinity Capture-MS), HERC2 (Affinity Capture-MS), FGD6 (Affinity Capture-MS), ECI2 (Affinity Capture-MS), CMAS (Affinity Capture-MS), USP20 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), SH2D4A (Two-hybrid), DBNL (Co-fractionation), DBNL (Affinity Capture-MS), DBNL (Proximity Label-MS), DBNL (Affinity Capture-MS), FGD6 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ3, A1A5Q0, A6H7G2, D3Z8X7, D3ZND0, F1LM81, O14976, O60308, O70523, P51114, P51116, P70501, P97874, P98175, Q16643, Q2V2M9, Q2VUH7, Q3UHZ5, Q5BJ56, Q5F4B2, Q5FVK6, Q5T0F9, Q5T1M5, Q60902, Q61584, Q62418, Q66HA5, Q68FU8, Q69ZX6, Q6GM14, Q6P1N0, Q6P9Q6, Q7SYB5, Q7ZXQ9, Q80U87, Q80V31, Q8BRN9, Q8CH02, Q8IWZ8, Q8K1A6

Diamond homologs: A0A0G2JV04, A0JNB0, A1A5H8, A1CEK6, A1DFN5, A1Y2K1, A2QW93, A3LXQ8, A4RF61, A5D8S5, A6H7G2, A6QLK6, A7MBI0, D3ZG83, F1RDG9, O13154, O42287, O43125, O55043, O74749, O75791, O89100, P00523, P00525, P00526, P00528, P05480, P06241, P09324, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P15054, P25020, P27446, P27447

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZAP70	up-regulates	DBNL	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Cargo recognition for clathrin-mediated endocytosis	6	9.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	153
Likely benign	61
Benign	6

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2030700	NM_000290.4(PGAM2):c.160del (p.Ile54fs)	Pathogenic
2136502	NM_000290.4(PGAM2):c.538C>T (p.Arg180Ter)	Pathogenic
2792686	NM_000290.4(PGAM2):c.173C>G (p.Ser58Ter)	Pathogenic
3616403	NM_000290.4(PGAM2):c.211del (p.Leu71fs)	Pathogenic
3633329	NM_000290.4(PGAM2):c.74G>A (p.Trp25Ter)	Pathogenic
4805042	NM_000290.4(PGAM2):c.163del (p.Cys55fs)	Pathogenic
548650	NM_000290.4(PGAM2):c.637G>A (p.Gly213Arg)	Likely pathogenic

SpliceAI

2289 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44044780:GCC:G	donor_gain	1.0000
7:44044803:G:GT	donor_gain	1.0000
7:44051826:GCAGA:G	acceptor_loss	1.0000
7:44051827:CAG:C	acceptor_gain	1.0000
7:44051828:A:AG	acceptor_gain	1.0000
7:44051828:AGA:A	acceptor_gain	1.0000
7:44051828:AGAG:A	acceptor_gain	1.0000
7:44051829:G:GA	acceptor_gain	1.0000
7:44051829:GA:G	acceptor_gain	1.0000
7:44051829:GAG:G	acceptor_gain	1.0000
7:44051829:GAGG:G	acceptor_gain	1.0000
7:44052865:A:AG	acceptor_gain	1.0000
7:44052866:G:GG	acceptor_gain	1.0000
7:44052866:GAC:G	acceptor_gain	1.0000
7:44052866:GACA:G	acceptor_gain	1.0000
7:44052941:GGTAA:G	donor_loss	1.0000
7:44052943:T:G	donor_loss	1.0000
7:44056863:A:T	donor_gain	1.0000
7:44056880:G:GT	donor_gain	1.0000
7:44056900:AGTGG:A	donor_loss	1.0000
7:44056901:GTG:G	donor_gain	1.0000
7:44056901:GTGGT:G	donor_loss	1.0000
7:44056902:TGG:T	donor_loss	1.0000
7:44056904:G:GG	donor_gain	1.0000
7:44056904:G:T	donor_loss	1.0000
7:44056905:T:G	donor_loss	1.0000
7:44057777:TACA:T	acceptor_loss	1.0000
7:44057780:A:AG	acceptor_gain	1.0000
7:44057780:A:T	acceptor_loss	1.0000
7:44057780:AG:A	acceptor_gain	1.0000

AlphaMissense

2834 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44051929:T:A	V80D	1.000
7:44060845:T:A	W408R	1.000
7:44060845:T:C	W408R	1.000
7:44060847:G:C	W408C	1.000
7:44060847:G:T	W408C	1.000
7:44060885:T:C	F421S	1.000
7:44051932:T:C	L81P	0.999
7:44051940:T:A	W84R	0.999
7:44051940:T:C	W84R	0.999
7:44052871:G:A	G86D	0.999
7:44056779:C:A	A117E	0.999
7:44060127:C:A	A376D	0.999
7:44060133:C:A	A378D	0.999
7:44060144:T:C	Y382H	0.999
7:44060789:A:T	E389V	0.999
7:44060798:T:C	F392S	0.999
7:44060816:T:A	I398N	0.999
7:44060816:T:C	I398T	0.999
7:44060816:T:G	I398S	0.999
7:44060846:G:C	W408S	0.999
7:44060848:T:A	W409R	0.999
7:44060848:T:C	W409R	0.999
7:44060852:G:C	R410P	0.999
7:44060854:G:C	G411R	0.999
7:44060855:G:A	G411D	0.999
7:44060879:G:A	G419D	0.999
7:44060884:T:C	F421L	0.999
7:44060885:T:G	F421C	0.999
7:44060886:C:A	F421L	0.999
7:44060886:C:G	F421L	0.999

dbSNP variants (sampled 300 via entrez): RS1000009538 (7:44044189 T>G), RS1000192172 (7:44063800 T>C), RS1000268209 (7:44063431 G>A,T), RS1000281497 (7:44058075 G>A), RS1000435799 (7:44047242 T>A,C), RS1000635929 (7:44064009 T>A), RS1000855245 (7:44064643 C>T), RS1000901391 (7:44053607 T>C), RS1001161504 (7:44064839 G>A,T), RS1001231252 (7:44062712 C>T), RS1001477237 (7:44050759 C>A,T), RS1001570610 (7:44044561 G>A,C), RS1001598433 (7:44044649 T>G), RS1001599028 (7:44062487 C>T), RS1001599944 (7:44047195 T>C)

Disease associations

OMIM: gene MIM:610106 | disease phenotypes: MIM:261670

GenCC curated gene-disease

Mondo (1): glycogen storage disease due to phosphoglycerate mutase deficiency (MONDO:0009865)

Orphanet (1): Glycogen storage disease due to phosphoglycerate mutase deficiency (Orphanet:97234)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1304	Blood protein levels	2.000000e-18
GCST012020_13	Serum metabolite levels	1.000000e-16
GCST012020_14	Serum metabolite levels	2.000000e-13

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536176	Dimauro disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067399 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.23	Kd	5.902	nM	CHEMBL5653589
8.23	ED50	5.902	nM	CHEMBL5653589
6.88	Kd	132.6	nM	CHEMBL3752910
6.88	ED50	132.6	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148198: Binding affinity to human DBNL incubated for 45 mins by Kinobead based pull down assay	kd	0.0059	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148198: Binding affinity to human DBNL incubated for 45 mins by Kinobead based pull down assay	kd	0.1326	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression	2
Nickel	increases expression	2
Smoke	decreases expression	2
Tunicamycin	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
ceric oxide	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone	increases cleavage, decreases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases cleavage, decreases reaction	1
Air Pollutants	affects expression, increases abundance	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
CHEMBL5651240	Binding	Binding affinity to human DBNL incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy