This gene encodes a large protein that maintains normal ciliary structure and is involved in the genetic cascade governing left-right organ specification, including regulation of NODAL, LEFTY and PITX2 expression. Mutations cause autosomal recessive microcephaly, short stature, and polymicrogyria with seizures. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.741 OMIM phenotype
Clinical SummaryRTTN
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Gene-Disease Validity (ClinGen)
microcephalic primordial dwarfism due to RTTN deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 3.97
OE 0.61 (0.500.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.11Z-score
OE missense 0.99 (0.941.04)
1124 obs / 1134.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.500.74)
00.351.4
Missense OE0.99 (0.941.04)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 73 / 120.0Missense obs/exp: 1124 / 1134.1Syn Z: -0.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRTTN-related bilateral diffuse polymicrogyriaOTHERAR

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

DN
0.6356th %ile
GOF
0.5269th %ile
LOF
0.3551th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RTTN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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