LLPH

Summary

LLPH (LLP homolog, long-term synaptic facilitation factor, HGNC:28229) is a protein-coding gene on chromosome 12q14.3, encoding Protein LLP homolog (Q9BRT6). In hippocampal neurons, regulates dendritic and spine growth and synaptic transmission. It is a selective cancer dependency (DepMap: 50.3% of cell lines).

Enables RNA binding activity. Predicted to be involved in dendrite extension and positive regulation of dendritic spine development. Located in chromosome and nucleolus.

Source: NCBI Gene 84298 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 50.3% of screened cell lines
• MANE Select transcript: NM_032338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28229
Approved symbol	LLPH
Name	LLP homolog, long-term synaptic facilitation factor
Location	12q14.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC14817, hLLP
Ensembl gene	ENSG00000139233
Ensembl biotype	protein_coding
OMIM	616998
Entrez	84298

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000266604, ENST00000446587, ENST00000921898, ENST00000921899

RefSeq mRNA: 1 — MANE Select: NM_032338 NM_032338

CCDS: CCDS8974

Canonical transcript exons

ENST00000266604 — 3 exons

Exon	Start	End
ENSE00001158366	66116555	66124018
ENSE00001208035	66130705	66130750
ENSE00003592110	66128896	66129113

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 93.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.1303 / max 2703.4951, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131927	45.1303	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	93.70	gold quality
right adrenal gland	UBERON:0001233	92.53	gold quality
right adrenal gland cortex	UBERON:0035827	92.50	gold quality
monocyte	CL:0000576	92.42	gold quality
leukocyte	CL:0000738	92.33	gold quality
left adrenal gland	UBERON:0001234	91.77	gold quality
left adrenal gland cortex	UBERON:0035825	91.24	gold quality
islet of Langerhans	UBERON:0000006	91.00	gold quality
adrenal gland	UBERON:0002369	90.38	gold quality
vermiform appendix	UBERON:0001154	89.87	gold quality
endothelial cell	CL:0000115	89.65	silver quality
gastrocnemius	UBERON:0001388	89.00	gold quality
adrenal cortex	UBERON:0001235	88.97	gold quality
smooth muscle tissue	UBERON:0001135	88.92	gold quality
rectum	UBERON:0001052	88.75	gold quality
granulocyte	CL:0000094	88.72	gold quality
mucosa of transverse colon	UBERON:0004991	88.65	gold quality
muscle of leg	UBERON:0001383	88.49	gold quality
calcaneal tendon	UBERON:0003701	87.85	gold quality
descending thoracic aorta	UBERON:0002345	87.61	gold quality
stromal cell of endometrium	CL:0002255	87.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.28	gold quality
left coronary artery	UBERON:0001626	86.93	gold quality
left testis	UBERON:0004533	86.69	gold quality
right testis	UBERON:0004534	86.57	gold quality
tibial artery	UBERON:0007610	86.55	gold quality
popliteal artery	UBERON:0002250	86.54	gold quality
thoracic aorta	UBERON:0001515	86.51	gold quality
mucosa of stomach	UBERON:0001199	86.48	gold quality
pancreas	UBERON:0001264	86.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting LLPH, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-4800-3P	88.42	63.07	35

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis. (PMID:33583303)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Llph	ENSMUSG00000020224
rattus_norvegicus	Llph-ps1	ENSRNOG00000004316

Protein

Protein identifiers

Protein LLP homolog — Q9BRT6 (reviewed: Q9BRT6)

Alternative names: Protein LAPS18-like

All UniProt accessions (1): Q9BRT6

UniProt curated annotations — full annotation on UniProt →

Function. In hippocampal neurons, regulates dendritic and spine growth and synaptic transmission.

Subunit / interactions. Interacts with CTCF, MYO1C and with the transcriptional machinery, including RNA polymerase II and TBP.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Similarity. Belongs to the learning-associated protein family.

RefSeq proteins (1): NP_115714* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018784	LLPH-like	Family

Pfam: PF10169

UniProt features (8 total): region of interest 2, compositionally biased region 2, cross-link 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
8FKW	ELECTRON MICROSCOPY	2.5
8FL3	ELECTRON MICROSCOPY	2.53
8FL7	ELECTRON MICROSCOPY	2.55
8FLB	ELECTRON MICROSCOPY	2.55
8FLD	ELECTRON MICROSCOPY	2.58
8FKX	ELECTRON MICROSCOPY	2.59
8FL6	ELECTRON MICROSCOPY	2.62
8FLA	ELECTRON MICROSCOPY	2.63
8FLF	ELECTRON MICROSCOPY	2.65
8FKY	ELECTRON MICROSCOPY	2.67
8FL2	ELECTRON MICROSCOPY	2.67
8FL9	ELECTRON MICROSCOPY	2.75
8FLC	ELECTRON MICROSCOPY	2.76
8IDT	ELECTRON MICROSCOPY	2.8
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8RL2	ELECTRON MICROSCOPY	2.84
8FL4	ELECTRON MICROSCOPY	2.89
8FL0	ELECTRON MICROSCOPY	2.91
8IDY	ELECTRON MICROSCOPY	3
8INF	ELECTRON MICROSCOPY	3
8FKZ	ELECTRON MICROSCOPY	3.04
9QIW	ELECTRON MICROSCOPY	3.04
6LU8	ELECTRON MICROSCOPY	3.13
8INE	ELECTRON MICROSCOPY	3.2
8INK	ELECTRON MICROSCOPY	3.2
8IPD	ELECTRON MICROSCOPY	3.2
8IPY	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRT6-F1	74.92	0.36

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 (2): 67, 74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_GROWTH, GOBP_NEUROGENESIS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_DEVELOPMENTAL_CELL_GROWTH, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_DEVELOPMENTAL_GROWTH_INVOLVED_IN_MORPHOGENESIS, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (2): positive regulation of dendritic spine development (GO:0060999), dendrite extension (GO:0097484)

GO Molecular Function (3): obsolete basal RNA polymerase II transcription machinery binding (GO:0001099), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): chromosome (GO:0005694), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
positive regulation of developmental process	1
dendritic spine development	1
regulation of dendritic spine development	1
neuron projection extension	1
nucleic acid binding	1
binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LLPH	MSRB3	Q8IXL7	564
LLPH	RFX8	Q6ZV50	528
LLPH	SHISAL1	Q3SXP7	484
LLPH	ACSS3	Q9H6R3	462
LLPH	LRRTM4	Q86VH4	460
LLPH	PIGQ	Q9BRB3	457
LLPH	THOC1	Q96FV9	443
LLPH	TMBIM4	Q9HC24	432
LLPH	HELB	Q8NG08	430
LLPH	ZNF593	O00488	424
LLPH	ASIC2	Q16515	412
LLPH	FRMD3	A2A2Y4	407
LLPH	OR52I2	Q8NH67	391
LLPH	MEIS1	O00470	379
LLPH	PATE2	Q6UY27	373

IntAct

66 interactions, top by confidence:

A	B	Type	Score
KRI1	LLPH	psi-mi:“MI:0915”(physical association)	0.560
ZFP41	LLPH	psi-mi:“MI:0915”(physical association)	0.560
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
Ctcf	RPL36A	psi-mi:“MI:0915”(physical association)	0.400
NFIC	LLPH	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
OAS3	PTBP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZC3HAV1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
CNBP	NOP56	psi-mi:“MI:0914”(association)	0.350
rep	URB1	psi-mi:“MI:0914”(association)	0.350
N	MRPL45	psi-mi:“MI:0914”(association)	0.350
EIF2AK2	NKRF	psi-mi:“MI:0914”(association)	0.350
SRPK3	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SRPK2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
DDX21	RPS3A	psi-mi:“MI:0914”(association)	0.350
ILF3	RPS3A	psi-mi:“MI:0914”(association)	0.350
IPO5	C11orf98	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RPL11	RPS3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (170): LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Two-hybrid), LLPH (Reconstituted Complex), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Affinity Capture-MS), LLPH (Proximity Label-MS), LLPH (Affinity Capture-MS)

ESM2 similar proteins: A5JSS4, B1MTI8, O88892, P02641, P06398, P09739, P0C0A9, P12620, P45378, P84101, P84102, Q05310, Q0UVD1, Q148I0, Q1E554, Q28HN4, Q28IN9, Q2KIT1, Q2TBR9, Q2TBV6, Q32P76, Q3E7B7, Q4I5Z5, Q5R5J3, Q5R6N0, Q5R7C4, Q5R8X8, Q5REM2, Q5ZHK9, Q68EY7, Q6DD17, Q6GNG8, Q6NVR5, Q6PHE8, Q75NG9, Q7SDA6, Q7ZY35, Q8MKI3, Q8NHG7, Q8R1F0

Diamond homologs: B0FRH7, Q2TBR9, Q3B748, Q5ZHK9, Q6NVR5, Q7ZY35, Q9BRT6, Q9D945, Q9GNQ1

SIGNOR signaling

0 interactions.

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
Peptide chain elongation	9	22.4×	1e-08
Viral mRNA Translation	9	22.4×	1e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	9	22.1×	1e-08
Selenocysteine synthesis	9	21.2×	1e-08
Eukaryotic Translation Termination	9	21.2×	1e-08
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	9	20.8×	1e-08
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	9	20.8×	1e-08
Formation of a pool of free 40S subunits	9	19.8×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of viral genome replication	7	36.4×	9e-08
cytoplasmic translation	10	25.7×	1e-09
ribosomal small subunit biogenesis	7	22.1×	3e-06
rRNA processing	11	21.6×	1e-09
translation	11	15.7×	1e-08
negative regulation of translation	5	13.6×	2e-03
response to virus	5	10.0×	7e-03
defense response to virus	8	7.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

419 predictions. Top by Δscore:

Variant	Effect	Δscore
12:66123865:TTC:T	donor_gain	0.9900
12:66123866:T:A	donor_gain	0.9900
12:66123910:G:A	donor_gain	0.9900
12:66124016:CAT:C	acceptor_gain	0.9900
12:66124017:ATC:A	acceptor_loss	0.9900
12:66124018:TC:T	acceptor_loss	0.9900
12:66124019:C:CC	acceptor_gain	0.9900
12:66124019:CTG:C	acceptor_loss	0.9900
12:66124020:T:A	acceptor_loss	0.9900
12:66128953:C:CT	donor_gain	0.9900
12:66129109:TTTAC:T	acceptor_gain	0.9900
12:66129110:TTAC:T	acceptor_gain	0.9900
12:66129111:TAC:T	acceptor_gain	0.9900
12:66129112:ACCT:A	acceptor_loss	0.9900
12:66129113:CCT:C	acceptor_loss	0.9900
12:66129113:CCTGA:C	acceptor_loss	0.9900
12:66129114:C:CC	acceptor_gain	0.9900
12:66129114:C:CG	acceptor_loss	0.9900
12:66129114:CT:C	acceptor_loss	0.9900
12:66129115:T:A	acceptor_loss	0.9900
12:66129120:T:C	acceptor_gain	0.9900
12:66130702:CA:C	donor_loss	0.9900
12:66130703:A:AC	donor_gain	0.9900
12:66130703:A:AT	donor_loss	0.9900
12:66130704:C:CC	donor_gain	0.9900
12:66123894:T:A	donor_gain	0.9800
12:66123929:G:A	donor_gain	0.9800
12:66124023:A:C	acceptor_gain	0.9800
12:66128893:CAC:C	donor_loss	0.9800
12:66128894:A:T	donor_loss	0.9800

AlphaMissense

870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:66123944:A:G	W96R	0.997
12:66123944:A:T	W96R	0.997
12:66129053:T:A	R18S	0.996
12:66129053:T:G	R18S	0.996
12:66129098:T:A	K3N	0.996
12:66129098:T:G	K3N	0.996
12:66129067:G:T	R14S	0.995
12:66129074:T:A	R11S	0.995
12:66129074:T:G	R11S	0.995
12:66129083:C:A	K8N	0.994
12:66129083:C:G	K8N	0.994
12:66123942:C:A	W96C	0.993
12:66123942:C:G	W96C	0.993
12:66129054:C:G	R18T	0.993
12:66129064:C:G	A15P	0.993
12:66129102:G:A	A2V	0.993
12:66129066:C:G	R14P	0.992
12:66129086:A:C	S7R	0.992
12:66129086:A:T	S7R	0.992
12:66129088:T:G	S7R	0.992
12:66123845:A:G	W129R	0.991
12:66123845:A:T	W129R	0.991
12:66123949:G:T	P94Q	0.991
12:66129099:T:A	K3I	0.991
12:66129075:C:G	R11T	0.990
12:66129095:G:C	S4R	0.990
12:66129095:G:T	S4R	0.990
12:66129097:T:G	S4R	0.990
12:66123958:C:T	G91E	0.989
12:66129077:T:A	K10N	0.989

dbSNP variants (sampled 300 via entrez): RS1000010516 (12:66123040 G>A,T), RS1000171863 (12:66125731 C>A), RS1000510915 (12:66124166 A>G), RS1000685194 (12:66118890 G>C), RS1000686338 (12:66116738 C>T), RS1000907572 (12:66116945 C>G), RS1001007430 (12:66130683 A>C), RS1001105569 (12:66123894 T>C), RS1001179172 (12:66123623 G>A), RS1001254963 (12:66117217 T>A), RS1001411052 (12:66129566 T>C), RS1001671920 (12:66130386 C>G), RS1001762658 (12:66117514 T>C), RS1002120186 (12:66129201 T>C), RS1002176683 (12:66122834 CG>C)

Disease associations

OMIM: gene MIM:616998 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003943_2	Hepcidin levels	6.000000e-07
GCST003989_44	Chin dimples	6.000000e-09
GCST004387_4	Pulse pressure	8.000000e-09
GCST90020026_496	Hip index	5.000000e-09
GCST90020028_986	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
Air Pollutants	increases abundance, decreases expression, increases expression, affects expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
resorcinol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, decreases expression, increases expression	1
Ribonucleotides	affects binding	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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