LARP7

La ribonucleoprotein 7, transcriptional regulator, the group of RNA binding motif containing|7SK snRNP complex|La ribonucleoproteins

Basic information

Region (hg38): 4:112637077-112657696

Links

ENSG00000174720 ∙ NCBI:51574 ∙ OMIM:612026 ∙ HGNC:24912 ∙ Uniprot:Q4G0J3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephalic primordial dwarfism, Alazami type (Definitive), mode of inheritance: AR
• microcephalic primordial dwarfism, Alazami type (Moderate), mode of inheritance: AR
• microcephalic primordial dwarfism, Alazami type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alazami syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	22865833; 30006060

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LARP7 gene.

• not provided (28 variants)
• Microcephalic primordial dwarfism, Alazami type (11 variants)
• LARP7-related disorder (1 variants)
• Alazami-Yuan syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LARP7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				43	1	44
missense		1	70	7	3	81
nonsense	10	1				11
start loss						0
frameshift	26	13	1			40
inframe indel	1		11	1		13
splice donor/acceptor (+/-2bp)		4				4
splice region		3	4	10	1	18
non coding			3	25	20	48
Total	37	19	85	76	24

Highest pathogenic variant AF is 0.0000592

Variants in LARP7

This is a list of pathogenic ClinVar variants found in the LARP7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-112644678-T-C			Likely benign (Oct 13, 2023)
4-112644679-G-A		not specified	Benign (Jan 31, 2024)
4-112644692-A-G		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
4-112644703-A-G			Uncertain significance (Aug 22, 2022)
4-112644723-AAAG-A			Uncertain significance (Jun 17, 2023)
4-112644730-AAAG-A		LARP7-related disorder	Likely benign (Jan 25, 2024)
4-112644731-AAG-A		Microcephalic primordial dwarfism, Alazami type • LARP7-related disorder	Pathogenic (Oct 12, 2023)
4-112644733-GA-G			Pathogenic (Oct 16, 2023)
4-112644734-A-T		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
4-112644758-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2023)
4-112644786-T-TA		Microcephalic primordial dwarfism, Alazami type	Pathogenic/Likely pathogenic (Mar 03, 2023)
4-112644810-G-T		LARP7-related disorder	Likely benign (Dec 21, 2023)
4-112644817-A-C			Uncertain significance (Apr 16, 2021)
4-112644860-C-A			Uncertain significance (Oct 20, 2021)
4-112644863-G-A			Uncertain significance (Oct 20, 2021)
4-112644881-C-T			Likely benign (Mar 03, 2023)
4-112644886-GTAAAGGAACCAATTTTTAGATATGGTTGCCTT-G			Likely benign (Jun 14, 2022)
4-112645135-T-C			Benign (Nov 12, 2018)
4-112646005-G-GTT			Benign (Jun 20, 2021)
4-112646332-A-C			Likely benign (Apr 26, 2023)
4-112646332-AC-A			Likely benign (Dec 12, 2023)
4-112646334-TTTTTCATTTTCTTTAGATGTTGATATATCACTACTTGTGTC-T		Microcephalic primordial dwarfism, Alazami type	Likely pathogenic (Jan 04, 2016)
4-112646338-T-C			Likely benign (Jul 25, 2022)
4-112646348-T-G		LARP7-related disorder	Uncertain significance (Dec 07, 2021)
4-112646356-G-GAT		Microcephalic primordial dwarfism, Alazami type	Pathogenic (Dec 21, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LARP7	protein_coding	protein_coding	ENST00000509061	13	20629

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.34e-8	0.982	125628	0	120	125748	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.268	297	284	1.04	0.0000134	3890
Missense in Polyphen		74	97.722	0.75725		1392
Synonymous	-2.06	118	92.7	1.27	0.00000438	1025
Loss of Function	2.22	16	28.9	0.554	0.00000141	422

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000780	0.000752
Ashkenazi Jewish	0.000333	0.000298
East Asian	0.000575	0.000544
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.000625	0.000580
Middle Eastern	0.000575	0.000544
South Asian	0.000714	0.000653
Other	0.000734	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system. Within the 7SK RNP complex, the positive transcription elongation factor b (P-TEFb) is sequestered in an inactive form, preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. {ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18483487}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:21937992, ECO:0000269|PubMed:22865833}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.969
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.46

Haploinsufficiency Scores

• pHI: 0.499
• hipred: Y
• hipred_score: 0.659
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Larp7
• Phenotype: growth/size/body region phenotype; cellular phenotype; embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: larp7
• Affected structure: atrium
• Phenotype tag: abnormal
• Phenotype quality: dilated

Gene ontology

• Biological process: RNA processing
• Cellular component: nucleoplasm;cytosol;ribonucleoprotein complex
• Molecular function: RNA binding;protein binding