LARP7

Chr 4AR

La ribonucleoprotein 7, transcriptional regulator

Also known as: ALAZS, HDCMA18P, PIP7S, hLARP7

NCBI Gene: 51574ENSG00000174720UniProt: Q4G0J3

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]

Primary Disease Associations & Inheritance

Alazami syndromeMIM #615071
AR
387
ClinVar variants
98
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LARP7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 146 VUS of 387 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.22
OE 0.55 (0.37–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.27Z-score
OE missense 1.04 (0.95–1.15)
297 obs / 284.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.37–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.95–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.27
0≤1.21.6
LoF obs/exp: 16 / 28.9Missense obs/exp: 297 / 284.3Syn Z: -2.06

ClinVar Variant Classifications

387 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic32
VUS146
Likely Benign112
Benign24
Conflicting7
66
Pathogenic
32
Likely Pathogenic
146
VUS
112
Likely Benign
24
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
42
0
24
0
66
Likely Pathogenic
23
2
7
0
32
VUS
5
116
23
2
146
Likely Benign
0
7
48
57
112
Benign
0
3
21
0
24
Conflicting
—7
Total7012812359387

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LARP7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LARP7-related Alazami syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Alazami syndrome

MIM #615071

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteogenomic insights into the biology and treatment of pancreatic ductal adenocarcinoma.
Tong Y et al.·J Hematol Oncol
2022
Functional Characterization of Variants in LARP7: Report of Three New Individuals With Alazami Syndrome and a Literature Review.
Ambrose A et al.·Hum Mutat
2025Review
Glucose-regulating hydrogel for immune modulation and angiogenesis through metabolic reprogramming and LARP7-SIRT1 pathway in infected diabetic wounds.
Liao Y et al.·Biomaterials
2025
Further phenotypic delineation of Alazami syndrome.
Al-Hinai A et al.·Am J Med Genet A
2022Case report
Broadening the phenotypic spectrum of pathogenic LARP7 variants: two cases with intellectual disability, variable growth retardation and distinct facial features.
Hollink IH et al.·J Hum Genet
2016Case report
[Clinical and genetic analysis of a child with Alazami syndrome due to compound heterozygous variants of LARP7 gene].
Yuan L et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Novel Mutation in LARP7 in Two Iranian Consanguineous Families with Syndromic Intellectual Disability and Facial Dysmorphism.
Kazemi G et al.·Arch Iran Med
2020Case report
Alazami syndrome: the first case of papillary thyroid carcinoma.
Ivanovski I et al.·J Hum Genet
2020Case report
Interaction of the Ankyrin H Core Effector of Legionella with the Host LARP7 Component of the 7SK snRNP Complex.
Von Dwingelo J et al.·mBio
2019
Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing.
Palumbo P et al.·Genes (Basel)
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools