PHLDB2

Summary

PHLDB2 (pleckstrin homology like domain family B member 2, HGNC:29573) is a protein-coding gene on chromosome 3q13.2, encoding Pleckstrin homology-like domain family B member 2 (Q86SQ0). Seems to be involved in the assembly of the postsynaptic apparatus.

Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cytoskeleton; and focal adhesion.

Source: NCBI Gene 90102 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 185 total
• MANE Select transcript: NM_001134438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29573
Approved symbol	PHLDB2
Name	pleckstrin homology like domain family B member 2
Location	3q13.2
Locus type	gene with protein product
Status	Approved
Aliases	LL5beta, FLJ21791, LL5b
Ensembl gene	ENSG00000144824
Ensembl biotype	protein_coding
OMIM	610298
Entrez	90102

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 59 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000393923, ENST00000393925, ENST00000412622, ENST00000431670, ENST00000460365, ENST00000470699, ENST00000477695, ENST00000478584, ENST00000478733, ENST00000478922, ENST00000481953, ENST00000486886, ENST00000491694, ENST00000495180, ENST00000498699, ENST00000638331, ENST00000640181, ENST00000640905, ENST00000878043, ENST00000878044, ENST00000878045, ENST00000878046, ENST00000878047, ENST00000878048, ENST00000878049, ENST00000878050, ENST00000878051, ENST00000878052, ENST00000878053, ENST00000878054, ENST00000878055, ENST00000878056, ENST00000878057, ENST00000878058, ENST00000878059, ENST00000932392, ENST00000932393, ENST00000932394, ENST00000932395, ENST00000948955, ENST00000948956, ENST00000948957, ENST00000948958, ENST00000948959, ENST00000948960, ENST00000948961, ENST00000948962, ENST00000948963, ENST00000948964, ENST00000948965, ENST00000948966, ENST00000948967, ENST00000948968, ENST00000948969, ENST00000948970, ENST00000948971, ENST00000948972, ENST00000948973, ENST00000948974, ENST00000948975, ENST00000948976, ENST00000948977, ENST00000948978, ENST00000948979, ENST00000948980

RefSeq mRNA: 4 — MANE Select: NM_001134438 NM_001134437, NM_001134438, NM_001134439, NM_145753

CCDS: CCDS2962, CCDS46885, CCDS46886

Canonical transcript exons

ENST00000431670 — 18 exons

Exon	Start	End
ENSE00001157435	111919072	111919215
ENSE00001157443	111913319	111913702
ENSE00001200343	111932269	111932397
ENSE00001229851	111920282	111920419
ENSE00001937056	111974423	111976517
ENSE00002207614	111953930	111954029
ENSE00002281359	111952572	111952712
ENSE00003530150	111967678	111967824
ENSE00003538999	111966613	111966703
ENSE00003553142	111945268	111945357
ENSE00003564576	111884064	111885412
ENSE00003576097	111973732	111973817
ENSE00003584856	111940535	111940645
ENSE00003596089	111948932	111949075
ENSE00003613895	111962108	111962312
ENSE00003637245	111969690	111969909
ENSE00003638241	111939475	111939630
ENSE00003889011	111859265	111859576

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0878 / max 459.4716, expressed in 1505 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37891	7.6289	1280
37885	6.4553	1043
37880	2.5577	214
37889	2.1453	924
37896	1.0953	138
37888	0.8027	515
37887	0.6390	295
37894	0.2617	115
37890	0.1652	64
37886	0.1602	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.44	gold quality
kidney epithelium	UBERON:0004819	98.84	gold quality
cauda epididymis	UBERON:0004360	98.32	gold quality
myocardium	UBERON:0002349	97.95	gold quality
parietal pleura	UBERON:0002400	97.76	gold quality
placenta	UBERON:0001987	97.70	gold quality
calcaneal tendon	UBERON:0003701	97.67	gold quality
decidua	UBERON:0002450	97.62	gold quality
heart right ventricle	UBERON:0002080	97.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.35	gold quality
popliteal artery	UBERON:0002250	97.10	gold quality
tibial artery	UBERON:0007610	97.10	gold quality
visceral pleura	UBERON:0002401	96.93	gold quality
seminal vesicle	UBERON:0000998	96.45	gold quality
germinal epithelium of ovary	UBERON:0001304	96.35	gold quality
cardiac ventricle	UBERON:0002082	96.33	gold quality
right coronary artery	UBERON:0001625	96.31	gold quality
heart left ventricle	UBERON:0002084	96.29	gold quality
tendon	UBERON:0000043	96.23	gold quality
apex of heart	UBERON:0002098	96.18	gold quality
skin of hip	UBERON:0001554	96.08	gold quality
adipose tissue	UBERON:0001013	96.06	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.71	gold quality
superficial temporal artery	UBERON:0001614	95.67	gold quality
aorta	UBERON:0000947	95.60	gold quality
saphenous vein	UBERON:0007318	95.59	gold quality
left coronary artery	UBERON:0001626	95.49	gold quality
sural nerve	UBERON:0015488	95.49	gold quality
urinary bladder	UBERON:0001255	95.44	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	19.66
E-MTAB-6142	no	125.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting PHLDB2, 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-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548D-3P	99.87	70.67	4362

Literature-anchored findings (GeneRIF, showing 14)

• LL5beta and ELKS can form a PIP3-regulated cortical platform to which CLASPs attach distal microtubule ends. (PMID:16824950)
• LL5beta directs the translocation of filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2. (PMID:20236936)
• Signaling from laminin-integrin associations in epithelial cells attaches microtubule plus ends to the epithelial basal cell cortex via PHLDB1 and PHLDB2. (PMID:20513769)
• minor allele, A, intronic single nucleotide polymorphism ‘rs951660’in PHLDB2 might induce a delayed splicing and increase the susceptibility to Vascular dementia (PMID:22111664)
• These and other LL5beta-interacting proteins are associated with conventional podosomes in macrophages and podosome-like invadopodia in fibroblasts, strengthening the close relationship between synaptic and non-synaptic podosomes. (PMID:23525008)
• Liprin-alpha1, ERC1a and LL5 also define new highly polarized and dynamic cytoplasmic structures uniquely localized near the protruding cell edge (PMID:24982445)
• Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5beta, and to promote microtubule targeting of focal adhesions. (PMID:27378169)
• Collectively, our findings present the first to elucidate that miR-29c is a direct p53 target gene, and also identify PHLDB2 as an important miR-29c target gene involved in colon cancer metastasis. (PMID:28392396)
• Oncometabolite L-2-hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma. (PMID:33320958)
• NOTCH3, a crucial target of miR-491-5p/miR-875-5p, promotes gastric carcinogenesis by upregulating PHLDB2 expression and activating Akt pathway. (PMID:33452458)
• RNA-seq-Based Screening in Coal Dust-Treated Cells Identified PHLDB2 as a Novel Lung Cancer-Related Molecular Marker. (PMID:34337001)
• PHLDB2 Mediates Cetuximab Resistance via Interacting With EGFR in Latent Metastasis of Colorectal Cancer. (PMID:34952201)
• Interfering with the ERC1-LL5beta interaction disrupts plasma membrane-Associated platforms and affects tumor cell motility. (PMID:37437062)
• Depletion of PHLDB2 Suppresses Epithelial-Mesenchymal Transition and Enhances Anti-Tumor Immunity in Head and Neck Squamous Cell Carcinoma. (PMID:38397469)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	phldb2b	ENSDARG00000074843
danio_rerio	phldb2a	ENSDARG00000079889
mus_musculus	Phldb2	ENSMUSG00000033149
rattus_norvegicus	Phldb2	ENSRNOG00000002171
drosophila_melanogaster	dos	FBGN0016794
caenorhabditis_elegans		WBGENE00004928

Paralogs (7): PHLDB1 (ENSG00000019144), GAB2 (ENSG00000033327), GAB1 (ENSG00000109458), PLEKHS1 (ENSG00000148735), GAB3 (ENSG00000160219), PHLDB3 (ENSG00000176531), GAB4 (ENSG00000215568)

Protein

Protein identifiers

Pleckstrin homology-like domain family B member 2 — Q86SQ0 (reviewed: Q86SQ0)

Alternative names: Protein LL5-beta

All UniProt accessions (8): Q86SQ0, A0A1W2PQ63, A0A1W2PRJ2, A0A1W2PRT1, E9PDY7, E9PFQ4, E9PGF6, G5E9V3

UniProt curated annotations — full annotation on UniProt →

Function. Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane.

Subunit / interactions. Interacts with FLNC. Interacts with AMOTL2; interaction may facilitate PHLDB2 localization to the myotube podosome cortex that surrounds the core. Part of a cortical microtubule stabilization complex (CMSC) composed of KANK1, PPFIA1, PPFIBP1, ERC1/ELKS, PHLDB2/LL5beta, CLASPs, KIF21A and possibly additional interactors; within CMSCs KANK1 and PHLDB2/LL5beta appear to be the core components for targeting of microtubule-binding proteins KIF21A and CLASPs, whereas PPFIA1, PPFIBP1 and ERC1/ELKS serve as scaffolds for protein clustering.

Subcellular location. Cytoplasm. Cell cortex. Membrane. Cell projection. Podosome.

Domain organisation. The PH domain mediates the binding to phosphoinositides.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86SQ0-1	1	yes
Q86SQ0-2	2
Q86SQ0-3	3

RefSeq proteins (4): NP_001127909, NP_001127910, NP_001127911, NP_665696 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR037810	PHLDB1/2/3_PH	Domain
IPR052212	PH-like_domain	Family

Pfam: PF00169

UniProt features (44 total): modified residue 23, region of interest 5, compositionally biased region 4, sequence conflict 3, coiled-coil region 3, splice variant 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8WHJ	X-RAY DIFFRACTION	1.4
8WHM	X-RAY DIFFRACTION	2.3
8WHK	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SQ0-F1	59.39	0.26

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 (23): 71, 73, 157, 204, 212, 242, 245, 330, 334, 348, 351, 384, 387, 415, 420, 468, 489, 501, 504, 513 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
1162–1163	loss of binding to ptdins(3,4,5)p3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 242 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_FOCAL_ADHESION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS

GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), cell migration (GO:0016477), establishment of cell polarity (GO:0030010), establishment of protein localization (GO:0045184), negative regulation of stress fiber assembly (GO:0051497), negative regulation of focal adhesion assembly (GO:0051895), basement membrane organization (GO:0071711), negative regulation of wound healing, spreading of epidermal cells (GO:1903690)

GO Molecular Function (2): cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (12): podosome (GO:0002102), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), cell leading edge (GO:0031252), intermediate filament cytoskeleton (GO:0045111), basal cortex (GO:0045180), cytoplasm (GO:0005737), focal adhesion (GO:0005925), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
cell periphery	2
cytoskeleton organization	1
microtubule-based process	1
cell motility	1
establishment or maintenance of cell polarity	1
establishment of localization	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
negative regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
negative regulation of cell-substrate junction organization	1
negative regulation of cell junction assembly	1
extracellular matrix organization	1
negative regulation of cell migration	1
wound healing, spreading of epidermal cells	1
negative regulation of wound healing	1
regulation of wound healing, spreading of epidermal cells	1
cell adhesion molecule binding	1
binding	1
actin-based cell projection	1
membrane	1
cytoskeleton	1
basal part of cell	1
cell cortex region	1
intracellular anatomical structure	1
cell-substrate junction	1
cell junction	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHLDB2	CLASRP	Q8N2M8	989
PHLDB2	ERC1	Q8IUD2	985
PHLDB2	PPFIA1	Q13136	905
PHLDB2	KANK1	Q14678	894
PHLDB2	CLASP2	O75122	882
PHLDB2	FLNC	Q14315	808
PHLDB2	PRICKLE1	Q96MT3	739
PHLDB2	KIF21A	Q7Z4S6	659
PHLDB2	TLN2	Q9Y4G6	647
PHLDB2	TLN1	Q9Y490	645
PHLDB2	CLIP1	P30622	632
PHLDB2	CLASP1	Q7Z460	597
PHLDB2	PPFIA3	O75145	576
PHLDB2	FLNA	P21333	567
PHLDB2	PLEK2	Q9NYT0	553

IntAct

163 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PHLDB2	FLNA	psi-mi:“MI:0915”(physical association)	0.560
FLNA	PHLDB2	psi-mi:“MI:0915”(physical association)	0.560
PHLDB2	USP7	psi-mi:“MI:0915”(physical association)	0.550
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
LZTS2	UNC119B	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PHLDB2		psi-mi:“MI:0403”(colocalization)	0.460
	PHLDB2	psi-mi:“MI:0915”(physical association)	0.460
PHLDB2		psi-mi:“MI:0915”(physical association)	0.460
PATL1	PHLDB2	psi-mi:“MI:0915”(physical association)	0.400
PHLDB2	CLASP1	psi-mi:“MI:0915”(physical association)	0.400
Cep135		psi-mi:“MI:0914”(association)	0.350

BioGRID (194): PHLDB2 (Affinity Capture-MS), PHLDB2 (Biochemical Activity), PHLDB2 (Proximity Label-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS), PHLDB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HFX9, A0A2R6X6S3, A0JM08, A0JNL1, A0JPQ1, A3KP40, A4QNZ7, B5XBI1, E2QSX5, E7F555, E9Q309, F1MCY2, F1QIC4, O75167, P04370, P0CAX8, P0CJ62, Q13522, Q32NP7, Q3T044, Q4KMC9, Q501J7, Q52KW0, Q5F368, Q5F3P8, Q5R8Q8, Q5RAU1, Q5SS90, Q5SW79, Q5U2R6, Q5VT06, Q6A065, Q6PEI3, Q6RFY2, Q80TN7, Q80Z38, Q86SQ0, Q8C1B1, Q8C3W1, Q8IVL0

Diamond homologs: A6QLU3, Q00IB7, Q13480, Q2WGN9, Q86SQ0, Q8BUL6, Q8K1N2, Q8WWW8, Q99PF6, Q9EQH1, Q9HB21, Q9QYY0, Q9ULM0, Q9UQC2, Q9VZZ9, Q9W5D0, Q9Z1S8, A0A0G2JUG7, A2A5R2, A5PKW4, A6H7I5, B6RSP1, D3ZL52, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, G5EGS5, O08967, O13817, O43739, O46382, P08567, P11075, P31749

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	52.2×	2e-10
Activation of BAD and translocation to mitochondria	7	51.7×	3e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	45.6×	8e-09
Activation of BH3-only proteins	7	33.7×	5e-08
RHO GTPases activate PKNs	8	24.6×	5e-08
Intrinsic Pathway for Apoptosis	7	19.9×	2e-06
RAF activation	6	19.6×	2e-05
Signaling by high-kinase activity BRAF mutants	6	18.5×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
substantia nigra development	8	20.8×	4e-06
protein targeting	7	18.2×	4e-05
intracellular protein localization	12	8.9×	6e-06
MAPK cascade	8	8.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	6
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

5016 predictions. Top by Δscore:

Variant	Effect	Δscore
3:111913316:CA:C	acceptor_loss	1.0000
3:111913317:A:G	acceptor_loss	1.0000
3:111913685:C:CG	donor_gain	1.0000
3:111913685:C:G	donor_gain	1.0000
3:111919159:GAACT:G	donor_gain	1.0000
3:111919198:GA:G	donor_gain	1.0000
3:111919211:GAGAG:G	donor_gain	1.0000
3:111919213:GAG:G	donor_gain	1.0000
3:111919214:AGGT:A	donor_loss	1.0000
3:111919215:GGTAA:G	donor_loss	1.0000
3:111919216:G:A	donor_loss	1.0000
3:111919217:T:A	donor_loss	1.0000
3:111920277:CTTA:C	acceptor_loss	1.0000
3:111920279:TAGTT:T	acceptor_loss	1.0000
3:111920280:A:AG	acceptor_gain	1.0000
3:111920280:AGTT:A	acceptor_gain	1.0000
3:111920280:AGTTG:A	acceptor_gain	1.0000
3:111920281:G:A	acceptor_loss	1.0000
3:111920281:G:GA	acceptor_gain	1.0000
3:111920281:GT:G	acceptor_gain	1.0000
3:111920281:GTT:G	acceptor_gain	1.0000
3:111920281:GTTG:G	acceptor_gain	1.0000
3:111920281:GTTGG:G	acceptor_gain	1.0000
3:111920415:CCAAG:C	donor_loss	1.0000
3:111920416:CAAG:C	donor_loss	1.0000
3:111920417:AAG:A	donor_loss	1.0000
3:111920418:AGGTA:A	donor_loss	1.0000
3:111920420:G:A	donor_loss	1.0000
3:111920421:T:A	donor_loss	1.0000
3:111932252:T:TA	acceptor_gain	1.0000

AlphaMissense

8316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:111939523:T:C	F727L	1.000
3:111939524:T:C	F727S	1.000
3:111939525:C:A	F727L	1.000
3:111939525:C:G	F727L	1.000
3:111939533:T:C	L730P	1.000
3:111966657:T:C	L1041P	1.000
3:111966668:G:C	A1045P	1.000
3:111966690:T:C	L1052P	1.000
3:111967730:G:C	R1074P	1.000
3:111969810:T:C	C1146R	1.000
3:111969812:C:G	C1146W	1.000
3:111969816:G:A	G1148R	1.000
3:111969816:G:C	G1148R	1.000
3:111969817:G:A	G1148E	1.000
3:111969823:T:C	L1150P	1.000
3:111969852:T:A	W1160R	1.000
3:111969852:T:C	W1160R	1.000
3:111969854:G:C	W1160C	1.000
3:111969854:G:T	W1160C	1.000
3:111969862:G:C	R1163P	1.000
3:111969864:T:A	W1164R	1.000
3:111969864:T:C	W1164R	1.000
3:111969868:T:C	F1165S	1.000
3:111969871:T:A	V1166D	1.000
3:111974445:T:C	F1215S	1.000
3:111974451:T:A	V1217D	1.000
3:111974484:C:A	A1228D	1.000
3:111974510:T:A	W1237R	1.000
3:111974510:T:C	W1237R	1.000
3:111974517:A:T	D1239V	1.000

dbSNP variants (sampled 300 via entrez): RS1000004124 (3:111856283 C>A), RS1000017609 (3:111915217 T>C), RS1000021267 (3:111900734 G>A,T), RS1000026746 (3:111840439 T>G), RS1000027355 (3:111810073 G>A), RS1000066133 (3:111818607 C>G), RS1000082221 (3:111907426 G>T), RS1000083637 (3:111890614 C>T), RS1000088172 (3:111902206 A>T), RS1000096100 (3:111763073 G>C), RS1000098480 (3:111768472 C>T), RS1000111320 (3:111740307 A>G), RS1000116784 (3:111855912 T>C), RS1000132389 (3:111972377 G>A,C), RS1000132762 (3:111972168 A>G)

Disease associations

OMIM: gene MIM:610298 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000579_15	Cognitive performance	5.000000e-06
GCST002729_7	Crohn’s disease-related phenotypes	2.000000e-06
GCST006061_143	Atrial fibrillation	5.000000e-11
GCST006061_57	Atrial fibrillation	3.000000e-11
GCST006414_80	Atrial fibrillation	2.000000e-15
GCST007045_23	PR interval	2.000000e-08
GCST010321_115	PR interval	7.000000e-17
GCST010796_5187	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_5188	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004462	PR interval
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	6
sodium arsenite	decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
Silver	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases methylation	1

Clinical trials (associated diseases)

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