LARP7

protein-coding

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

Gene summary

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. [provided by RefSeq, May 2012]

MANE transcript

NM_016648.4

Inheritance

ClinVar variants

P:103U:135B:66

Top phenotype

Alazami syndrome

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr4:112,637,077-112,657,696

External References & Databases

Ensembl (ENSG00000174720)

Transcript & Mutation Effects

hg38 • Region Span ~20.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephalic primordial dwarfism, Alazami typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014031

Submitter: Ambry Genetics

microcephalic primordial dwarfism, Alazami typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014031

Submitter: G2P

microcephalic primordial dwarfism, Alazami typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014031

Submitter: PanelApp Australia

microcephalic primordial dwarfism, Alazami typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014031

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Alazami syndromeAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 22865833; 30006060

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LARP7 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 254

Inborn genetic diseasesTotal: 87

Microcephalic primordial dwarfism, Alazami typeTotal: 62

LARP7-related disorderTotal: 18

not specifiedTotal: 14

Intellectual disabilityTotal: 5

Paediatric disordersTotal: 2

Epileptic encephalopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016648.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	57 clinvar		59
missense		2 clinvar	127 clinvar	8 clinvar	1 clinvar	138
nonsense	6 clinvar	7 clinvar				13
start loss						0
frameshift	45 clinvar	29 clinvar	2 clinvar			76
splice donor/acceptor (+/-2bp)	3 clinvar	11 clinvar	4 clinvar			18
Total	54	49	135	65	1	304

Highest pathogenic variant AF is 0.00005637918

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 127 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016648.4	RefSeq	NP_057732.2	12	MANE Select
ENST00000344442.10	Ensembl	ENSP00000344950.5	12	MANE Select
NM_001267039.4	RefSeq	NP_001253968.2	12	Standard
NM_001370974.1	RefSeq	NP_001357903.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
larp7	Danio rerio	Structure: atrium Quality: dilated abnormal

Gene / Model

Organism

Observed Phenotype

larp7

Danio rerio

Structure: atrium

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

RNA processing

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
cytosol
ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000509061
Coding exons: 13
Length: 20629
Individuals with no LoFs: 125628
Homozygous LoFs: 0
Heterozygous LoFs: 120
Defined: 125748
p: 0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.268	297	284	1.04	0.0000134	3890
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00052	0.00049	rare
Latino/Admixed American	0.00026	0.00023	rare
Ashkenazi Jewish	0.00033	0.00030	rare
East Asian	0.00058	0.00054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00062	0.00058	rare
South Asian	0.00071	0.00065	rare
Other	0.00073	0.00065	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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