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…

LOEUF 0.22

Clinical Summary— RTL9

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

167 VUS of 220 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

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

ClinVar Variant Classifications

220 submitted variants in ClinVar

ClinVar

Classification Summary

VUS167

Likely Benign14

Conflicting2

167

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	167	0	0	167
Likely Benign	0	12	0	2	14
Benign	0	0	0	0	0
Conflicting	—				2
Total	0	179	0	2	183

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

View in ClinVar →

72 pathogenic / likely-pathogenic (of 80) ClinVar copy-number / structural variants overlap RTL9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →