LARP7

Chr 4

La ribonucleoprotein 7, transcriptional regulator

Also known as: ALAZS, HDCMA18P, PIP7S, hLARP7

NCBI Gene: 51574 ENSG00000174720 UniProt: Q4G0J3

The LARP7 protein binds to specific small nuclear RNAs (7SK and U6 snRNAs) and regulates RNA polymerase II transcriptional elongation and mRNA splicing fidelity through its roles in ribonucleoprotein complexes. Biallelic mutations cause Alazami syndrome, an autosomal recessive disorder. This gene shows low constraint against loss-of-function variants (pLI near zero).

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.84

Clinical Summary— LARP7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

88 unique Pathogenic / Likely Pathogenic· 143 VUS of 384 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.22

OE 0.55 (0.37–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.27Z-score

OE missense 1.04 (0.95–1.15)

297 obs / 284.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.37–0.84)

0≤0.351.4

Missense OE?1.04 (0.95–1.15)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 16 / 28.9Missense obs/exp: 297 / 284.3Syn Z: -2.06

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveLARP7-related Alazami syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6646th %ile

GOF

0.4777th %ile

LOF

0.4429th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

384 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56

Likely Pathogenic32

VUS143

Likely Benign112

Benign24

Conflicting7

Pathogenic

Likely Pathogenic

143

VUS

112

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	54	0	2	0	56
Likely Pathogenic	29	2	1	0	32
VUS	5	128	8	2	143
Likely Benign	0	9	46	57	112
Benign	0	3	21	0	24
Conflicting	—				7
Total	88	142	78	59	374

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap LARP7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →