AHI1

Chr 6AR

Abelson helper integration site 1

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

NCBI Gene: 54806 ENSG00000135541 UniProt: Q8N157 OMIM: 608894

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.951 OMIM phenotype

Clinical Summary— AHI1

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Gene-Disease Validity (ClinGen)

Joubert syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

287 unique Pathogenic / Likely Pathogenic· 632 VUS of 1793 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — AHI1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.88

OE 0.75 (0.59–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.03Z-score

OE missense 1.00 (0.94–1.07)

598 obs / 595.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.59–0.95)

0≤0.351.4

Missense OE?1.00 (0.94–1.07)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 48 / 64.3Missense obs/exp: 598 / 595.6Syn Z: -0.48

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAHI1-related Joubert syndromeLOFAR

This gene — mechanism propensity

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

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

1793 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic156

Likely Pathogenic131

VUS632

Likely Benign691

Benign60

Conflicting91

156

Pathogenic

131

Likely Pathogenic

632

VUS

691

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	129	8	18	1	156
Likely Pathogenic	109	17	5	0	131
VUS	6	540	76	10	632
Likely Benign	0	25	356	310	691
Benign	0	1	57	2	60
Conflicting	—				91
Total	244	591	512	323	1,761

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap AHI1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →