LRRC7

Summary

LRRC7 (leucine rich repeat containing 7, HGNC:18531) is a protein-coding gene on chromosome 1p31.1, encoding Leucine-rich repeat-containing protein 7 (Q96NW7). Required for normal synaptic spine architecture and function.

Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and protein localization to membrane. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. Implicated in cocaine dependence.

Source: NCBI Gene 57554 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 221 total — 10 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 160
• MANE Select transcript: NM_001370785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18531
Approved symbol	LRRC7
Name	leucine rich repeat containing 7
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1365, densin-180
Ensembl gene	ENSG00000033122
Ensembl biotype	protein_coding
OMIM	614453
Entrez	57554

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 protein_coding, 2 retained_intron

ENST00000310961, ENST00000370958, ENST00000441830, ENST00000565615, ENST00000588515, ENST00000607936, ENST00000608470, ENST00000608744, ENST00000608815, ENST00000609072, ENST00000609498, ENST00000651217, ENST00000651989

RefSeq mRNA: 10 — MANE Select: NM_001370785 NM_001330635, NM_001350216, NM_001366836, NM_001366837, NM_001366838, NM_001366839, NM_001366840, NM_001366841, NM_001366842, NM_001370785

CCDS: CCDS81341, CCDS90974, CCDS90975

Canonical transcript exons

ENST00000651989 — 27 exons

Exon	Start	End
ENSE00001197358	69760191	69760393
ENSE00001640894	70043954	70044094
ENSE00001646339	70036444	70036624
ENSE00001650344	70089727	70089819
ENSE00001684180	70076077	70076298
ENSE00001737253	70107752	70107826
ENSE00001742903	70036121	70036232
ENSE00001767662	70053026	70053145
ENSE00001772161	70028171	70028371
ENSE00001789525	70038113	70039793
ENSE00001795187	70023126	70023374
ENSE00003466403	69838227	69838283
ENSE00003472542	69931507	69931570
ENSE00003491128	70016465	70016534
ENSE00003503967	70012974	70013089
ENSE00003534235	69825748	69825826
ENSE00003546152	70021005	70021129
ENSE00003563252	69678381	69678478
ENSE00003579817	69994561	69994633
ENSE00003599732	69834780	69834869
ENSE00003625823	69986242	69986386
ENSE00003670745	69980379	69980453
ENSE00003674376	70011797	70011926
ENSE00003680338	70018719	70018818
ENSE00003690100	69792043	69792160
ENSE00003845696	69567922	69568641
ENSE00003848258	70121780	70144364

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.18.

FANTOM5 (CAGE): breadth broad, TPM avg 8.1591 / max 727.3756, expressed in 395 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3450	1.8737	216
3456	1.7262	182
3442	0.8842	96
3443	0.7937	113
3449	0.6740	142
3441	0.5417	109
3452	0.3575	88
3446	0.2654	70
3459	0.2140	59
3458	0.1895	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.23	gold quality
primary visual cortex	UBERON:0002436	93.46	gold quality
nucleus accumbens	UBERON:0001882	92.75	gold quality
middle temporal gyrus	UBERON:0002771	92.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.95	gold quality
ganglionic eminence	UBERON:0004023	91.57	gold quality
caudate nucleus	UBERON:0001873	91.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.72	gold quality
putamen	UBERON:0001874	90.70	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.01	gold quality
occipital lobe	UBERON:0002021	89.82	gold quality
Ammon’s horn	UBERON:0001954	89.53	gold quality
cerebral cortex	UBERON:0000956	89.08	gold quality
anterior cingulate cortex	UBERON:0009835	88.93	gold quality
endothelial cell	CL:0000115	88.82	gold quality
prefrontal cortex	UBERON:0000451	88.75	gold quality
neocortex	UBERON:0001950	88.44	gold quality
right frontal lobe	UBERON:0002810	88.35	gold quality
frontal cortex	UBERON:0001870	88.13	gold quality
amygdala	UBERON:0001876	88.03	gold quality
superior frontal gyrus	UBERON:0002661	87.91	gold quality
temporal lobe	UBERON:0001871	87.55	gold quality
entorhinal cortex	UBERON:0002728	87.18	gold quality
secondary oocyte	CL:0000655	86.52	gold quality
forebrain	UBERON:0001890	86.28	gold quality
postcentral gyrus	UBERON:0002581	85.47	gold quality
parietal lobe	UBERON:0001872	84.60	gold quality
brain	UBERON:0000955	83.89	gold quality
hypothalamus	UBERON:0001898	83.76	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	51.49
E-HCAD-35	yes	28.62
E-GEOD-93593	yes	16.12
E-ANND-3	yes	6.66
E-MTAB-6108	no	262.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting LRRC7, 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-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-8082	99.95	67.27	1170

Literature-anchored findings (GeneRIF, showing 11)

• Densin-180 co-localized with delta-catenin/NPRAP at synapses in delta-catenin/NPRAP and may be involved in organization of the synaptic cell-cell junction through interaction with the delta-catenin/NPRAP-N-cadherin complex (PMID:11729199)
• A novel splice variant, LRRC7, of densin-180 is located on 1p31 and consists of 8 exons. Unlike wild type, not brain-specific. (PMID:12525888)
• expressed by glomerular podocytes and has a role in associating with the nephrin interacting protein complex at the slit diaphragm (PMID:12819232)
• Densin can act as autoantigen, and autoantibodies against these can be detected in patients with type 1 diabetes. (PMID:16741999)
• Densin is a novel testicular protein expressed in the cell membranes of Sertoli cells. (PMID:17039495)
• Densin may associate with the cadherin-catenin and nephrin complex(es), and may be involved in the formation of the cell-cell contacts. (PMID:17581699)
• common variants in LRRC7, KIRREL, NPHS2 and ACTN4 do not appeear to contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes (PMID:17968527)
• Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation. (PMID:21610080)
• We found no genome-wide statistically significant associations but identified several plausible candidate genes among findings at p < 5E-05: LRRC7, TMEM132D, SEMA3A, ALK, and STIP1. (PMID:21784300)
• The important role of this gene in the synapse and mental illness endophenotypes observed in animal models suggests that LRRC7 may play a role in susceptibility to bipolar disorder. (PMID:26901794)
• Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors. (PMID:39256359)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc7	ENSDARG00000079670
mus_musculus	Lrrc7	ENSMUSG00000028176
rattus_norvegicus	Lrrc7	ENSRNOG00000011980

Paralogs (31): PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 7 — Q96NW7 (reviewed: Q96NW7)

Alternative names: Densin-180, Protein LAP1

All UniProt accessions (7): A0A075B6E9, A0A494C1A4, B1AKT2, K7ELH5, V9GY23, V9GYE1, V9GZ42

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal synaptic spine architecture and function. Necessary for DISC1 and GRM5 localization to postsynaptic density complexes and for both N-methyl D-aspartate receptor-dependent and metabotropic glutamate receptor-dependent long term depression.

Subunit / interactions. Interacts with CNKSR2 and DLG4. Interacts with CTNND2/Catenin delta-2. Forms a complex with N-cadherin through CTNND2. Interacts with CAMK2A.

Subcellular location. Cytoplasm. Postsynaptic density.

Tissue specificity. Brain-specific. Isoform 3 is ubiquitously expressed.

Similarity. Belongs to the LAP (LRR and PDZ) protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96NW7-1	1	yes
Q96NW7-2	2
Q96NW7-3	3, LRRC7

RefSeq proteins (10): NP_001317564, NP_001337145, NP_001353765, NP_001353766, NP_001353767, NP_001353768, NP_001353769, NP_001353770, NP_001353771, NP_001357714* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR050614	Synaptic_Scaffolding_LAP-MAGUK	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF00595, PF13855, PF23598

UniProt features (61 total): repeat 17, modified residue 14, region of interest 7, compositionally biased region 7, strand 6, splice variant 3, sequence variant 2, chain 1, domain 1, sequence conflict 1, turn 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7QQM	X-RAY DIFFRACTION	1.6
6X5G	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NW7-F1	52.05	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 (14): 439, 441, 443, 831, 850, 865, 869, 947, 949, 1118, 1149, 1233, 1335, 1439

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6798695	Neutrophil degranulation
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 156 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_ENDOCYTIC_RECYCLING, GOCC_NEURON_PROJECTION, GOBP_PROTEIN_LOCALIZATION_TO_SYNAPSE, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (5): positive regulation of neuron projection development (GO:0010976), receptor clustering (GO:0043113), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), cell-cell adhesion (GO:0098609), neurotransmitter receptor transport, endosome to postsynaptic membrane (GO:0098887)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), cytosol (GO:0005829), adherens junction (GO:0005912), postsynaptic density (GO:0014069), basolateral plasma membrane (GO:0016323), specific granule lumen (GO:0035580), axon initial segment (GO:0043194), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), plasma membrane (GO:0005886), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1
Innate Immune System	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
plasma membrane	1
protein localization to membrane	1
establishment or maintenance of apical/basal cell polarity	1
cell adhesion	1
intercellular transport	1
neurotransmitter receptor transport to postsynaptic membrane	1
neurotransmitter receptor transport, endosome to plasma membrane	1
kinase binding	1
binding	1
cytoplasm	1
cell-cell junction	1
asymmetric synapse	1
postsynaptic specialization	1
basal plasma membrane	1
plasma membrane region	1
secretory granule lumen	1
specific granule	1
main axon	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC7	CAMK2A	Q9UQM7	917
LRRC7	CACNA1D	Q01668	784
LRRC7	CTNND2	Q9UQB3	726
LRRC7	PKP4	Q99569	680
LRRC7	SHANK3	Q9BYB0	649
LRRC7	CAMK2B	Q13554	637
LRRC7	SHANK2	Q9UPX8	636
LRRC7	ARVCF	O00192	609
LRRC7	CACNA1C	Q13936	605
LRRC7	NPHS1	O60500	573
LRRC7	CNKSR2	Q8WXI2	572
LRRC7	ACTN4	O43707	562
LRRC7	DLGAP1	P78335	562
LRRC7	NPHS2	Q9NP85	551
LRRC7	KIRREL1	Q96J84	545

IntAct

391 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LRRC7	PKP4	psi-mi:“MI:0915”(physical association)	0.610
LRRC7	CTNND2	psi-mi:“MI:0915”(physical association)	0.610
LRRC7	E	psi-mi:“MI:0915”(physical association)	0.610
CTNND2	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.610
PKP4	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.610
LRRC7	E	psi-mi:“MI:0407”(direct interaction)	0.610
ERBB2	LRRC7	psi-mi:“MI:0915”(physical association)	0.590
ERBB4	LRRC7	psi-mi:“MI:0915”(physical association)	0.590
CNKSR2	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.590
CFTR	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.570
SHANK1	LRRC7	psi-mi:“MI:0915”(physical association)	0.490
TOR1A	LRRC7	psi-mi:“MI:0915”(physical association)	0.490
LRRC7	TOR1A	psi-mi:“MI:0915”(physical association)	0.490
GAS2L2	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
ARVCF	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
Tax	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
TANC1	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
LRRC7	SLC15A5	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
GUCY1A2	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
LRRC7	WWTR1	psi-mi:“MI:0407”(direct interaction)	0.440
SLCO1C1	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
FAM110D	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
APC	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA1	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM151B	LRRC7	psi-mi:“MI:0407”(direct interaction)	0.440
LRRC7	TRPV3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (56): LRRC7 (Two-hybrid), HOMEZ (Two-hybrid), LRRC7 (Proximity Label-MS), LRRC7 (Affinity Capture-RNA), LRRC7 (Affinity Capture-MS), LRRC7 (Affinity Capture-MS), PPP1R9B (Reconstituted Complex), LRRC7 (Reconstituted Complex), HOMER3 (Two-hybrid), NQO2 (Two-hybrid), EPS15L1 (Two-hybrid), HOMEZ (Two-hybrid), LRRC7 (Two-hybrid), LRRC7 (Two-hybrid), LRRC7 (Two-hybrid)

ESM2 similar proteins: A1A5R8, A6H694, A6PVS8, B8A5Y1, D3Z6S9, F1MCA7, P62283, P62285, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, P62932, P70587, Q05C16, Q14DL3, Q3U3V8, Q3V0J4, Q497N7, Q4R3V2, Q4R739, Q4V8G0, Q53TS8, Q5CZC0, Q5RA75, Q6AXY2, Q6AYL8, Q6P2D8, Q6PUR7, Q7PCK7, Q7T3T8, Q7Z7J5, Q80TE7, Q86WZ0

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, A5PKA5, F1MCA7, G5ECY0, O14907, O14910, O35274, O35867, O55164, O61967, O62674, O62675, O62676, O88951, O88952, P31016, P57105, P70175, P70587, P78352, P97879, Q0P5E6, Q0P5F3, Q12959, Q13424, Q13425, Q13884, Q14160, Q15599, Q22638, Q28626, Q28C55, Q2KIB6, Q32LE7, Q32LM6, Q3T0C9, Q3UHD6, Q4H4B6, Q5EBL8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CAMK2A	unknown	LRRC7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 188 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
Neurexins and neuroligins	7	10.4×	3e-03
Transport of small molecules	17	3.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of excitatory postsynaptic potential	6	17.9×	9e-04
positive regulation of synaptic transmission, glutamatergic	5	17.6×	1e-03
cell-cell adhesion mediated by cadherin	6	13.9×	1e-03
adult behavior	5	13.2×	4e-03
synapse organization	6	9.5×	4e-03
transport across blood-brain barrier	8	8.1×	1e-03
protein-containing complex assembly	10	6.4×	1e-03
monoatomic ion transport	7	6.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	185
Likely benign	17
Benign	5

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
3901201	NM_001370785.2(LRRC7):c.2242C>T (p.Gln748Ter)	Pathogenic
3901202	NM_001370785.2(LRRC7):c.3266dup (p.Gln1091fs)	Pathogenic
4530023	NM_001370785.2(LRRC7):c.281A>G (p.Asn94Ser)	Pathogenic
4530024	NM_001370785.2(LRRC7):c.887T>C (p.Leu296Pro)	Pathogenic
4548003	Single allele	Pathogenic
4830051	Single allele	Pathogenic
4830343	Single allele	Pathogenic
4831341	Single allele	Pathogenic
4831703	Single allele	Pathogenic
4832086	Single allele	Pathogenic
4071962	NM_001370785.2(LRRC7):c.365T>G (p.Leu122Arg)	Likely pathogenic

SpliceAI

4309 predictions. Top by Δscore:

Variant	Effect	Δscore
1:69760390:CAAGG:C	donor_loss	1.0000
1:69760391:AAG:A	donor_loss	1.0000
1:69760392:AGG:A	donor_loss	1.0000
1:69792037:TTACA:T	acceptor_loss	1.0000
1:69792040:CAGC:C	acceptor_loss	1.0000
1:69792041:A:AG	acceptor_gain	1.0000
1:69792041:A:T	acceptor_loss	1.0000
1:69792042:G:GA	acceptor_gain	1.0000
1:69792042:G:GT	acceptor_loss	1.0000
1:69792042:GC:G	acceptor_gain	1.0000
1:69792042:GCA:G	acceptor_gain	1.0000
1:69792042:GCAA:G	acceptor_gain	1.0000
1:69792042:GCAAT:G	acceptor_gain	1.0000
1:69792158:ATGG:A	donor_loss	1.0000
1:69792159:TGG:T	donor_loss	1.0000
1:69792160:GGTAA:G	donor_loss	1.0000
1:69792161:G:GG	donor_gain	1.0000
1:69792161:GTAAG:G	donor_loss	1.0000
1:69792162:T:A	donor_loss	1.0000
1:69825827:G:GG	donor_gain	1.0000
1:69834778:A:AG	acceptor_gain	1.0000
1:69834779:G:GG	acceptor_gain	1.0000
1:69834869:GGT:G	donor_gain	1.0000
1:69834869:GGTAA:G	donor_loss	1.0000
1:69838284:G:GG	donor_gain	1.0000
1:69931567:GCTG:G	donor_gain	1.0000
1:69980366:A:AG	acceptor_gain	1.0000
1:69980367:C:G	acceptor_gain	1.0000
1:69980454:GTAT:G	donor_gain	1.0000
1:70011795:A:AG	acceptor_gain	1.0000

AlphaMissense

10418 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003409 (1:70054135 T>G), RS1000008454 (1:69819575 CTCTGTGTGTGTG>C), RS1000008735 (1:70076053 C>A,T), RS1000011216 (1:69629169 A>G), RS1000012925 (1:70134877 C>T), RS1000017986 (1:69817455 T>C), RS1000026994 (1:69779610 C>A), RS1000027752 (1:69687350 A>C), RS1000035511 (1:69691987 A>C), RS1000035754 (1:70121304 A>G), RS1000043783 (1:69879688 C>T), RS1000047915 (1:69613052 T>C), RS1000053069 (1:69953783 C>T), RS1000059299 (1:69862475 G>A), RS1000060052 (1:69732663 T>C)

Disease associations

OMIM: gene MIM:614453 | disease phenotypes: MIM:621415

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (3): intellectual disability (MONDO:0001071), intellectual developmental disorder, autosomal dominant 77 (MONDO:0980748), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

160 total (30 of 160 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000076	Vesicoureteral reflux
HP:0000098	Tall stature
HP:0000126	Hydronephrosis
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000201	Pierre-Robin sequence
HP:0000218	High palate
HP:0000240	Abnormality of skull size
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000283	Broad face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000486	Strabismus
HP:0000537	Epicanthus inversus
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000571	Hypometric saccades

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001154_6	Attention deficit hyperactivity disorder	4.000000e-06
GCST001405_1	Hypertension risk in short sleep duration	3.000000e-08
GCST001442_5	Orofacial clefts	9.000000e-06
GCST001442_8	Orofacial clefts	4.000000e-06
GCST001762_302	Obesity-related traits	6.000000e-06
GCST002301_6	Body mass index	2.000000e-06
GCST002889_1	Psoriasis	3.000000e-09
GCST003075_80	Cognitive decline rate in late mild cognitive impairment	7.000000e-08
GCST003075_97	Cognitive decline rate in late mild cognitive impairment	6.000000e-06
GCST007324_122	Adventurousness	2.000000e-08
GCST008114_31	Type 2 diabetes	7.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004340	body mass index
EFO:0007710	cognitive decline measurement
EFO:0008579	risk-taking behaviour

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	3
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation	2
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases methylation	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cocaine	affects response to substance	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Thimerosal	increases expression	1
S-Nitrosoglutathione	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4YU	SUi003-A	Induced pluripotent stem cell	Male
CVCL_A4YV	SUi003-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays