LARP7

Summary

LARP7 (La ribonucleoprotein 7, transcriptional regulator, HGNC:24912) is a protein-coding gene on chromosome 4q25, encoding La-related protein 7 (Q4G0J3). RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function.

This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51574 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephalic primordial dwarfism, Alazami type (Definitive, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 372 total — 54 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24912
Approved symbol	LARP7
Name	La ribonucleoprotein 7, transcriptional regulator
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	HDCMA18P, PIP7S, DKFZP564K112
Ensembl gene	ENSG00000174720
Ensembl biotype	protein_coding
OMIM	612026
Entrez	51574

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 38 protein_coding, 12 retained_intron, 9 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000344442, ENST00000503316, ENST00000503898, ENST00000504079, ENST00000505034, ENST00000505216, ENST00000507443, ENST00000508577, ENST00000509061, ENST00000509622, ENST00000511529, ENST00000512361, ENST00000512589, ENST00000513553, ENST00000651579, ENST00000684864, ENST00000685424, ENST00000685716, ENST00000688617, ENST00000689262, ENST00000689844, ENST00000690008, ENST00000692075, ENST00000692168, ENST00000692416, ENST00000693375, ENST00000693442, ENST00000694891, ENST00000694892, ENST00000694893, ENST00000694894, ENST00000694895, ENST00000694896, ENST00000694897, ENST00000694898, ENST00000694899, ENST00000694900, ENST00000694901, ENST00000694902, ENST00000895081, ENST00000895082, ENST00000895083, ENST00000895084, ENST00000895085, ENST00000895086, ENST00000895087, ENST00000895088, ENST00000895089, ENST00000895090, ENST00000895091, ENST00000895092, ENST00000926147, ENST00000926148, ENST00000926149, ENST00000926150, ENST00000926151, ENST00000969071, ENST00000969072, ENST00000969073, ENST00000969074, ENST00000969075

RefSeq mRNA: 12 — MANE Select: NM_016648 NM_001267039, NM_001370974, NM_001370975, NM_001370976, NM_001370977, NM_001370978, NM_001370979, NM_001370980, NM_001370981, NM_001370982, NM_015454, NM_016648

CCDS: CCDS3701, CCDS93568, CCDS93569, CCDS93570, CCDS93571

Canonical transcript exons

ENST00000344442 — 13 exons

Exon	Start	End
ENSE00002059299	112637143	112637239
ENSE00003517186	112653077	112653236
ENSE00003522604	112657247	112657586
ENSE00003524792	112647199	112647549
ENSE00003555792	112647690	112647834
ENSE00003563909	112647034	112647127
ENSE00003576461	112644668	112644871
ENSE00003598390	112649535	112649686
ENSE00003609857	112646791	112646955
ENSE00003645834	112654068	112654159
ENSE00003668693	112646351	112646451
ENSE00003668965	112650461	112650582
ENSE00003790574	112646588	112646671

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0250 / max 2282.2247, expressed in 1779 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49293	22.2630	1743
49295	12.5617	1637
49294	2.2003	1051

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.73	gold quality
monocyte	CL:0000576	96.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.53	gold quality
mononuclear cell	CL:0000842	96.41	gold quality
ventricular zone	UBERON:0003053	96.22	gold quality
leukocyte	CL:0000738	96.02	gold quality
tendon	UBERON:0000043	95.83	gold quality
sural nerve	UBERON:0015488	95.78	gold quality
rectum	UBERON:0001052	95.66	gold quality
ganglionic eminence	UBERON:0004023	94.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.71	gold quality
lower esophagus	UBERON:0013473	94.70	gold quality
right atrium auricular region	UBERON:0006631	94.62	gold quality
colonic epithelium	UBERON:0000397	94.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.26	gold quality
descending thoracic aorta	UBERON:0002345	94.23	gold quality
gall bladder	UBERON:0002110	94.16	gold quality
heart left ventricle	UBERON:0002084	94.10	gold quality
cardiac ventricle	UBERON:0002082	94.02	gold quality
metanephros cortex	UBERON:0010533	94.02	gold quality
body of uterus	UBERON:0009853	93.99	gold quality
popliteal artery	UBERON:0002250	93.78	gold quality
tibial artery	UBERON:0007610	93.78	gold quality
left ovary	UBERON:0002119	93.64	gold quality
transverse colon	UBERON:0001157	93.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.57	gold quality
sigmoid colon	UBERON:0001159	93.55	gold quality
left coronary artery	UBERON:0001626	93.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	2932.92
E-ANND-3	yes	8.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting LARP7, 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-150-5P	99.99	66.69	1976
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-6730-3P	97.03	67.54	889

Literature-anchored findings (GeneRIF, showing 27)

• Results identify PIP7S as a La-related protein stably associated with and required for 7SK snRNP integrity. (PMID:18249148)
• Results indicate LARP7 is a 7SK-binding protein. (PMID:18281698)
• Results suggest that LARP7 is a negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system. (PMID:18483487)
• A combination of restrictive chromatin structures at the HIV long terminal repeat and limiting P-TEFb levels contribute to transcriptional silencing leading to latency in primary CD4(+) T cells. (PMID:20410271)
• 7SK RNA thus establishes gene-dependent plasticity between HMGA1 chromatin remodeling and transcription initiation and P-TEFb transcription elongation. (PMID:21957495)
• LARP7 downregulation occurs early during gastric tumorigenesis and may promote gastric tumorigenesis via p-TEFb dysregulation. (PMID:22488152)
• Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism (PMID:22865833)
• Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb. (PMID:23340209)
• The results demonstrate that the La modules of the human LARP7 is also active in tRNA-mediated suppression, even in the absence of stable UUU-3’OH trailer protection. (PMID:23887937)
• LARP7 is most likely recruited to the HIV-1 promoter in the presence of hnRNP A1. (PMID:24607481)
• LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. (PMID:25053741)
• results suggest that LARP7 uses both its N- and C-terminal domains to stabilize 7SK in a closed structure, which forms by joining conserved sequences at the 5’-end with the foot of the 3’ hairpin and has thus functional implications (PMID:25753663)
• protein HEXIM with 7SKsnRNP complex comprising the non-coding RNA 7SK and proteins MePCE and LARP7. (PMID:25863285)
• LARP7 knockdown induces progressive time-dependent telomere shortening concomitant with a reduction in telomerase enzymatic activity and a decrease in full-length (catalytically active) TERT mRNA in vitro, and that humans with LARP7 deficiency display dramatically short telomeres, borderline anemia in younger generations, and anticipation consistent with a telomeropathy. (PMID:27766953)
• The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. (PMID:28254838)
• LARP7 may have inhibited the proliferation and increased the radioiodine uptake of PTC cells by regulating the SHH signaling pathway. (PMID:29620212)
• a structural model for Larp7 binding to the 7SK 3’ end and mechanism for 7SK RNP assembly. This work provides insight into how this domain contributes to 7SK recognition and assembly of the core 7SK RNP. (PMID:29946027)
• LARP7 functios as a bridging factor for snoRNA-guided modification of the U6 snRNA and alterations in splicing fidelity contribute to the etiology of the Alazami syndrome. (PMID:32017898)
• L ARP7 Is a BRCA1 Ubiquitinase Substrate and Regulates Genome Stability and Tumorigenesis. (PMID:32726637)
• Alazami syndrome: Phenotypic expansion and clinical resemblance to Smith-Lemli-Opitz syndrome. (PMID:32888391)
• Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins. (PMID:33131423)
• Novel Mutation in LARP7 in Two Iranian Consanguineous Families with Syndromic Intellectual Disability and Facial Dysmorphism. (PMID:33356342)
• Alazami syndrome: Report of three Indian patients with phenotypic spectrum from adolescence to adulthood. (PMID:33569879)
• LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis. (PMID:33663221)
• Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. (PMID:34107850)
• LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity. (PMID:34818543)
• LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis. (PMID:39009594)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	larp7	ENSDARG00000017315
mus_musculus	Larp7	ENSMUSG00000027968
mus_musculus	Larp7-ps	ENSMUSG00000066107
rattus_norvegicus	Larp7	ENSRNOG00000048989
drosophila_melanogaster	Larp7	FBGN0260771

Paralogs (6): LARP4B (ENSG00000107929), SSB (ENSG00000138385), LARP1B (ENSG00000138709), LARP1 (ENSG00000155506), LARP4 (ENSG00000161813), LARP6 (ENSG00000166173)

Protein

Protein identifiers

La-related protein 7 — Q4G0J3 (reviewed: Q4G0J3)

Alternative names: La ribonucleoprotein domain family member 7, P-TEFb-interaction protein for 7SK stability

All UniProt accessions (17): A0A8I5KQG7, A0A8I5KSZ3, A0A8I5KUI4, A0A8I5KYN2, A0A8Q3SHF1, A0A8Q3SHG9, A0A8Q3SHH4, A0A8Q3SHL6, A0A8Q3SHN7, A0A8Q3WK75, Q4G0J3, D6R9Z6, D6RBH8, D6RF22, D6RF49, D6RFF0, H0YA82

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function. Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II. The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC). LARP7 specifically binds to the highly conserved 3’-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex. LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing. Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2’-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes. U6 snRNA 2’-O-methylation is required for mRNA splicing fidelity. Binds U6 snRNAs with a 5’-CAGGG-3’ sequence motif. U6 snRNA processing is required for spermatogenesis.

Subunit / interactions. Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with METTL16. Interacts with RBM7; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core, yielding to P-TEFb complex activation. Associates with box C/D small nucleolar ribonucleoprotein (snoRNP) complexes.

Subcellular location. Nucleus. Nucleoplasm.

Disease relevance. Alazami syndrome (ALAZS) [MIM:615071] A syndromic form of primordial dwarfism, a condition characterized by severe growth restriction that has its onset in utero, and results in short stature and undersize. ALAZS patients manifest severe intellectual disability and distinct facial features including malar hypoplasia, deep-set eyes, broad nose, short philtrum, and macrostomia. Some patients have non-specific and inconsistent skeletal findings, for example, scoliosis and mild epiphyseal changes in the proximal phalanges, but no frank dysplasia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The xRRM domain binds the 3’ end of 7SK snRNA (7SK RNA) at the top of stem-loop 4.

Similarity. Belongs to the LARP7 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q4G0J3-1	1	yes
Q4G0J3-2	2
Q4G0J3-3	3

RefSeq proteins (12): NP_001253968, NP_001357903, NP_001357904, NP_001357905, NP_001357906, NP_001357907, NP_001357908, NP_001357909, NP_001357910, NP_001357911, NP_056269, NP_057732* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002344	Lupus_La	Family
IPR006630	La_HTH	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR014886	La_xRRM	Domain
IPR034887	LARP7_RRM1	Domain
IPR034910	LARP7_RRM2	Domain
IPR034946	LARP7_La	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045180	La_dom_prot	Family

Pfam: PF00076, PF05383, PF08777

UniProt features (65 total): helix 13, modified residue 11, strand 10, mutagenesis site 9, compositionally biased region 6, domain 3, sequence conflict 3, region of interest 3, cross-link 2, splice variant 2, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6D12	X-RAY DIFFRACTION	2.21
4WKR	X-RAY DIFFRACTION	3.2
7SLQ	ELECTRON MICROSCOPY	3.7
7SLP	ELECTRON MICROSCOPY	4.1
5KNW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0J3-F1	67.89	0.23

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 (13): 1, 257, 258, 261, 273, 298, 299, 300, 337, 338, 351, 237, 410

Mutagenesis-validated functional residues (9):

Position	Phenotype
44	reduced binding to u6 snrna without affecting binding to 7sk rna. reduced 2’-o-methylation of u6 snrnas.
128	loss of 7sk rna-binding and marked decrease in 7sk rnp complex formation.
130	decreased rna-binding.
168	does not affect rna-binding.
451	does not affect binding to the 7sk rna.
472	does not affect binding to the 7sk rna.
483	reduced binding to the 7sk rna. does not affect binding to u6 snrna.
483	does not affect binding to the 7sk rna.
496	strongly reduced binding to the stem loop 4 of 7sk rna.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 265 (showing top): chr4q25, PAL_PRMT5_TARGETS_UP, GOBP_SNO_S_RNA_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_RNA_METHYLATION, CEBPB_01, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOBP_RNA_MODIFICATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RNA_SPLICING, SCHLOSSER_SERUM_RESPONSE_DN

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), box C/D sno(s)RNA 3’-end processing (GO:0000494), mRNA processing (GO:0006397), spermatogenesis (GO:0007283), RNA splicing (GO:0008380), cell differentiation (GO:0030154), negative regulation of viral transcription (GO:0032897), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), regulation of mRNA splicing, via spliceosome (GO:0048024), positive regulation of protein localization to Cajal body (GO:1904871), positive regulation of snRNA transcription by RNA polymerase II (GO:1905382), U6 2’-O-snRNA methylation (GO:1990438), RNA processing (GO:0006396)

GO Molecular Function (5): RNA binding (GO:0003723), U6 snRNA binding (GO:0017070), 7SK snRNA binding (GO:0097322), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), 7SK snRNP (GO:0120259), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
snRNA binding	2
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
sno(s)RNA 3’-end processing	1
box C/D sno(s)RNA processing	1
mRNA metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
positive regulation of protein localization to nucleus	1
protein localization to Cajal body	1
regulation of protein localization to Cajal body	1
snRNA transcription by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
regulation of snRNA transcription by RNA polymerase II	1
snRNA 2’-O-methylation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
small nuclear ribonucleoprotein complex	1
protein-containing complex	1

Protein interactions and networks

STRING

3811 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LARP7	MEPCE	Q7L2J0	999
LARP7	HEXIM1	O94992	999
LARP7	HEXIM2	Q96MH2	997
LARP7	CDK9	P50750	975
LARP7	CCNT1	O60563	974
LARP7	CCNT2	O60583	903
LARP7	SART3	Q15020	819
LARP7	AFF1	P51825	807
LARP7	AFF4	Q9UHB7	795
LARP7	LARP4B	Q92615	771
LARP7	BRD4	O60885	756
LARP7	ELL2	O00472	741
LARP7	RBM8A	Q9Y5S9	741
LARP7	ELL	P55199	692
LARP7	MLLT1	Q03111	671

IntAct

243 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
HEXIM1	CDK9	psi-mi:“MI:0914”(association)	0.940
CDK9	LARP7	psi-mi:“MI:0915”(physical association)	0.930
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
tat	CCNT1	psi-mi:“MI:0914”(association)	0.780
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
DDX21	LARP7	psi-mi:“MI:0915”(physical association)	0.670
BRD4	CDK9	psi-mi:“MI:0914”(association)	0.660
LARP7		psi-mi:“MI:0914”(association)	0.660
	LARP7	psi-mi:“MI:0915”(physical association)	0.660
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.660
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640

BioGRID (1530): LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS), LARP7 (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A2CG63, B0S733, F1QNX7, G3V8T1, O75376, O94988, P29536, Q02040, Q14241, Q149C2, Q15695, Q15696, Q28G87, Q2KIC0, Q4FZU3, Q4G0J3, Q4KKX4, Q4LE39, Q4R627, Q53F19, Q561R3, Q5NCR9, Q5R4U2, Q5RL73, Q5U2T3, Q5XIN3, Q5ZM19, Q60974, Q62377, Q63187, Q64707, Q6PFK1, Q6PGZ3, Q8BZR9, Q8C761, Q8CB77, Q8K2X2, Q8QG78, Q8TDR0

Diamond homologs: A0A0D1C8Z4, A2Q848, A6NDY0, A8WLV5, B0BNE4, B3LYP1, B3P0D7, B4JUT1, B4KCD5, B4LZ88, O13620, O13741, O13845, O14327, O80678, P19683, P19684, P20397, P33240, P38922, P40561, P42696, P49313, P49314, Q00916, Q05AT9, Q05CL8, Q06106, Q08208, Q08937, Q09295, Q09301, Q10B98, Q1PEP5, Q28165, Q28ZX3, Q44554, Q44556, Q44560, Q4G0J3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
LARP7	“down-regulates activity”	HEXIM1	binding
LARP7	“down-regulates activity”	P-TEFb	binding
ATM	“down-regulates quantity by destabilization”	LARP7	phosphorylation
“BRCA1-BARD1 complex”	“down-regulates quantity by destabilization”	LARP7	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	28.0×	9e-06
SARS-CoV-2 modulates host translation machinery	11	20.5×	3e-10
Eukaryotic Translation Initiation	7	18.0×	1e-06
Cap-dependent Translation Initiation	7	18.0×	1e-06
SARS-CoV-1 modulates host translation machinery	7	18.0×	1e-06
Eukaryotic Translation Elongation	7	16.2×	3e-06
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	15.9×	3e-06
SRP-dependent cotranslational protein targeting to membrane	18	15.0×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	7	47.1×	1e-08
chromosome condensation	7	35.3×	1e-07
spliceosomal snRNP assembly	6	20.9×	3e-05
cytoplasmic translation	16	17.7×	5e-13
ribosomal small subunit biogenesis	11	15.0×	3e-08
positive regulation of transcription elongation by RNA polymerase II	8	14.4×	7e-06
ribosomal large subunit biogenesis	5	13.3×	2e-03
rRNA processing	15	12.7×	3e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	21
Uncertain significance	140
Likely benign	108
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070296	NM_016648.4(LARP7):c.1599G>A (p.Trp533Ter)	Pathogenic
1172609	NM_016648.3:c.392_997del	Pathogenic
1308663	NM_016648.4(LARP7):c.64_65del (p.Glu22fs)	Pathogenic
1308667	NM_016648.4(LARP7):c.789dup (p.Glu264Ter)	Pathogenic
1325791	NM_016648.4(LARP7):c.1045_1051dup (p.Ser351Ter)	Pathogenic
1335562	NM_016648.4(LARP7):c.1147G>T (p.Glu383Ter)	Pathogenic
1355037	NM_016648.4(LARP7):c.712_713del (p.Glu238fs)	Pathogenic
1374371	NM_016648.4(LARP7):c.878_896del (p.Gly293fs)	Pathogenic
1385262	NM_016648.4(LARP7):c.1166_1167del (p.Lys389fs)	Pathogenic
1458164	NM_016648.4(LARP7):c.1358del (p.Ser453fs)	Pathogenic
1458227	NM_016648.4(LARP7):c.825_834del (p.Lys275fs)	Pathogenic
1459435	NM_016648.4(LARP7):c.1055_1058del (p.Leu352fs)	Pathogenic
1526263	NM_016648.4(LARP7):c.690_699delinsTCCAAGCCAATAGACAATATCCAAGCC (p.Lys230_Asn233delinsAsnProSerGlnTer)	Pathogenic
1708490	NM_016648.4(LARP7):c.931_950del (p.Lys311fs)	Pathogenic
1801475	NM_016648.4(LARP7):c.225_226del (p.Ser76fs)	Pathogenic
1803676	NM_016648.4(LARP7):c.728_729dup (p.Ser244fs)	Pathogenic
1805499	NM_016648.4(LARP7):c.290C>A (p.Ser97Ter)	Pathogenic
1926459	NM_016648.4(LARP7):c.1227_1231del (p.Lys410fs)	Pathogenic
1957190	NM_016648.4(LARP7):c.461_462del (p.Ile154fs)	Pathogenic
1967475	NM_016648.4(LARP7):c.1010_1011del (p.Ser337fs)	Pathogenic
1986316	NM_016648.4(LARP7):c.377_378del (p.Thr126fs)	Pathogenic
2035314	NM_016648.4(LARP7):c.66del (p.Val23fs)	Pathogenic
2135121	NM_016648.4(LARP7):c.961dup (p.Ile321fs)	Pathogenic
2168966	NM_016648.4(LARP7):c.818C>G (p.Ser273Ter)	Pathogenic
2629784	NM_016648.4(LARP7):c.925C>T (p.Arg309Ter)	Pathogenic
2766195	NM_016648.4(LARP7):c.520G>T (p.Glu174Ter)	Pathogenic
2824153	NM_016648.4(LARP7):c.627dup (p.Pro210fs)	Pathogenic
2996235	NM_016648.4(LARP7):c.268dup (p.Ile90fs)	Pathogenic
2999617	NM_016648.4(LARP7):c.1491del (p.Phe497fs)	Pathogenic
3252951	NM_016648.4(LARP7):c.673_676del (p.Lys225fs)	Pathogenic

SpliceAI

2330 predictions. Top by Δscore:

Variant	Effect	Δscore
4:112637207:G:GG	donor_gain	1.0000
4:112637227:G:GT	donor_gain	1.0000
4:112637240:G:GG	donor_gain	1.0000
4:112644656:T:A	acceptor_gain	1.0000
4:112644659:A:AG	acceptor_gain	1.0000
4:112644660:A:G	acceptor_gain	1.0000
4:112644664:ACAG:A	acceptor_gain	1.0000
4:112644665:C:G	acceptor_gain	1.0000
4:112644665:CAGG:C	acceptor_loss	1.0000
4:112644666:A:AG	acceptor_gain	1.0000
4:112644666:AG:A	acceptor_gain	1.0000
4:112644667:G:GT	acceptor_gain	1.0000
4:112644667:GG:G	acceptor_gain	1.0000
4:112644667:GGA:G	acceptor_gain	1.0000
4:112644667:GGAA:G	acceptor_gain	1.0000
4:112644667:GGAAT:G	acceptor_gain	1.0000
4:112644754:TCAC:T	donor_gain	1.0000
4:112644867:TGGAT:T	donor_gain	1.0000
4:112644868:GGAT:G	donor_gain	1.0000
4:112644868:GGATG:G	donor_gain	1.0000
4:112644869:GAT:G	donor_gain	1.0000
4:112644869:GATG:G	donor_gain	1.0000
4:112644871:TG:T	donor_loss	1.0000
4:112644872:G:GG	donor_gain	1.0000
4:112644872:GTA:G	donor_loss	1.0000
4:112644873:T:G	donor_loss	1.0000
4:112646346:TTTAG:T	acceptor_loss	1.0000
4:112646347:TTAGA:T	acceptor_loss	1.0000
4:112646348:TAG:T	acceptor_loss	1.0000
4:112646349:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000077739 (4:112652833 G>A,T), RS1000356255 (4:112646771 T>C,G), RS1000556228 (4:112636197 T>G), RS1000683853 (4:112641135 T>G), RS1000855041 (4:112647944 T>C), RS1000925515 (4:112653989 T>C), RS1000958560 (4:112648113 T>C), RS1001083924 (4:112654200 T>G), RS1001109052 (4:112648125 G>A), RS1001138706 (4:112641330 G>C), RS1001535213 (4:112654569 C>G), RS1001546822 (4:112637348 C>G,T), RS1001732248 (4:112643023 A>C,G), RS1001733432 (4:112645768 T>C), RS1001866698 (4:112649354 C>G,T)

Disease associations

OMIM: gene MIM:612026 | disease phenotypes: MIM:615071

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephalic primordial dwarfism, Alazami type	Definitive	Autosomal recessive

Mondo (2): microcephalic primordial dwarfism, Alazami type (MONDO:0014031), intellectual disability (MONDO:0001071)

Orphanet (2): Alazami syndrome (Orphanet:319671), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000315	Abnormality of the orbital region
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000687	Widely spaced teeth
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000742	Self-mutilation
HP:0000965	Cutis marmorata
HP:0001072	Thickened skin
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001631	Atrial septal defect
HP:0002360	Sleep disturbance
HP:0002650	Scoliosis
HP:0003100	Slender long bone
HP:0003510	Severe short stature
HP:0004325	Decreased body weight
HP:0005280	Depressed nasal bridge
HP:0008897	Postnatal growth retardation
HP:0010535	Sleep apnea
HP:0010864	Severe intellectual disability

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005951_145	Body mass index	4.000000e-08
GCST009269_5	Dental caries (decayed and filled deciduous teeth)	3.000000e-06
GCST010143_1	Meat-related diet	3.000000e-08
GCST010701_20	Cortical surface area (MOSTest)	1.000000e-242
GCST010702_74	Subcortical volume (MOSTest)	2.000000e-11
GCST010703_129	Brain morphology (MOSTest)	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523314 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,781 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL428690	ALVOCIDIB	3	27,781

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Ki	3	nM	ALVOCIDIB

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 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
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	1572664: Inhibition of human recombinant P-TEFb expressed in baculovirus expression system after 10 mins by SDS-PAGE analysis	ki	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
trichostatin A	affects expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
pyrimidin-2-one beta-ribofuranoside	increases expression	1
kojic acid	decreases expression	1
beta-lapachone	increases expression	1
potassium chromate(VI)	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
tanespimycin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Clozapine	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4370693	Binding	Inhibition of human recombinant P-TEFb expressed in baculovirus expression system after 10 mins by SDS-PAGE analysis	A review on flavones targeting serine/threonine protein kinases for potential anticancer drugs. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
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
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
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)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders