AHI1

Chr 6AR

Abelson helper integration site 1

Also known as: AHI-1, JBTS3, ORF1, dJ71N10.1

The AHI1 protein is involved in vesicle trafficking and required for ciliogenesis, formation of primary cilia, and recruitment of RAB8A to the basal body, functioning as part of the tectonic-like complex at the ciliary transition zone. Mutations cause Joubert syndrome 3, a recessively inherited developmental brain disorder affecting cerebellar and cortical development. This gene follows autosomal recessive inheritance and is extremely intolerant to loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.951 OMIM phenotype
Clinical SummaryAHI1
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Gene-Disease Validity (ClinGen)
Joubert syndrome 3 · 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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ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 50 VUS of 100 total submissions
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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
0.95LOEUF
pLI 0.000
Z-score 1.88
OE 0.75 (0.590.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.03Z-score
OE missense 1.00 (0.941.07)
598 obs / 595.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.75 (0.590.95)
00.351.4
Missense OE1.00 (0.941.07)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 48 / 64.3Missense obs/exp: 598 / 595.6Syn Z: -0.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAHI1-related Joubert syndromeLOFAR

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

DN
0.6065th %ile
GOF
0.6931th %ile
LOF
0.4528th %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

100 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS50
Likely Benign37
Conflicting1
9
Pathogenic
3
Likely Pathogenic
50
VUS
37
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
0
0
9
Likely Pathogenic
3
0
0
0
3
VUS
0
47
2
1
50
Likely Benign
0
0
20
17
37
Benign
0
0
0
0
0
Conflicting
1
Total11482218100

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

View in ClinVar →

Protein Context — Lollipop Plot

AHI1 · 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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