RTL9

Chr X

retrotransposon Gag like 9

Also known as: MAR9, MART9, RGAG1, SIRH10

NCBI Gene: 57529 ENSG00000243978 UniProt: Q8NET4 OMIM: 300965

RTL9 encodes a retrotransposon-like protein involved in transcriptional regulation and chromatin organization. Mutations cause autosomal recessive developmental delay with seizures, intellectual disability, and growth retardation, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants, indicating that complete loss of RTL9 function is poorly tolerated.

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.22

LOEUF· LoF intol.

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.22LOEUF

pLI 0.997

Z-score 4.13

OE 0.05 (0.01–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

-0.67Z-score

OE missense 1.08 (1.01–1.16)

568 obs / 524.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.05 (0.01–0.22)

0≤0.351.4

Missense OE?1.08 (1.01–1.16)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 21.8Missense obs/exp: 568 / 524.9Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in RTL9?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,198 rare PASS variants

Rare truncating (LoF)

1 in 4,800

52 rare PASS variants

Rare synonymous (reference)

1 in 130

448 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RTL9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 82	1 in 4,000
South Asian	~36k	1 in 52	≈ 1 in 18,000
Remaining (unassigned)	~31k	1 in 45	1 in 6,100
European (Finnish)	~27k	1 in 170	≈ 1 in 6,600
Admixed American	~23k	1 in 55	1 in 2,200
African / African American	~21k	1 in 43	none seen
East Asian	~20k	1 in 51	≈ 1 in 6,700
Ashkenazi Jewish	~13k	1 in 430	none seen
Middle Eastern	~2,758	1 in 46	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓