AHI1

Abelson helper integration site 1, the group of WD repeat domain containing

Basic information

Region (hg38): 6:135283407-135498434

Links

ENSG00000135541 ∙ NCBI:54806 ∙ OMIM:608894 ∙ HGNC:21575 ∙ Uniprot:Q8N157 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 3 (Definitive), mode of inheritance: AR
• Joubert syndrome 3 (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with ocular defect (Supportive), mode of inheritance: AR
• retinitis pigmentosa (Limited), mode of inheritance: AR
• Joubert syndrome 3 (Strong), mode of inheritance: AR
• Joubert syndrome 3 (Definitive), mode of inheritance: AR
• Joubert syndrome 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 3	AR	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal system, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Neurologic; Ophthalmologic; Renal	15467982; 15322546; 16155189; 16453322; 20081859; 21937992; 25616960
The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AHI1 gene.

• Joubert_syndrome (1282 variants)
• Joubert_syndrome_3 (434 variants)
• not_provided (252 variants)
• Inborn_genetic_diseases (162 variants)
• not_specified (69 variants)
• AHI1-related_disorder (35 variants)
• Retinal_dystrophy (28 variants)
• Joubert_syndrome_and_related_disorders (21 variants)
• Retinitis_pigmentosa (9 variants)
• Intellectual_disability (7 variants)
• Joubert_syndrome_1 (6 variants)
• Joubert_syndrome_with_ocular_defect (5 variants)
• Rod-cone_dystrophy (4 variants)
• See_cases (4 variants)
• Nephronophthisis (3 variants)
• Optic_atrophy (3 variants)
• Leber_congenital_amaurosis (2 variants)
• Type_2_diabetes_mellitus (2 variants)
• Global_developmental_delay (1 variants)
• Typical_Joubert_syndrome_MRI_findings (1 variants)
• Retinal_disorders (1 variants)
• Abnormality_of_the_eye (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AHI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001134831.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		10	315	2	328
missense	9	23	526	60	1	619
nonsense	45	22				67
start loss						0
frameshift	78	47	3			128
splice donor/acceptor (+/-2bp)	8	41	3	1		53
Total	141	133	542	376	3

Highest pathogenic variant AF is 0.00011742705

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AHI1	protein_coding	protein_coding	ENST00000367800	25	214245

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-25	0.166	124467	0	186	124653	0.000746

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0346	598	596	1.00	0.0000299	7867
Missense in Polyphen		135	163.12	0.82762		2072
Synonymous	-0.484	206	197	1.04	0.00000953	2114
Loss of Function	1.88	48	64.3	0.747	0.00000359	827

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00174	0.00172
Ashkenazi Jewish	0.00	0.00
East Asian	0.000853	0.000835
Finnish	0.000662	0.000650
European (Non-Finnish)	0.000830	0.000796
Middle Eastern	0.000853	0.000835
South Asian	0.000401	0.000392
Other	0.00188	0.00182

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium. Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in neuronal differentiation. As a positive modulator of classical Wnt signaling, may play a crucial role in ciliary signaling during cerebellum embryonic development (PubMed:21623382). {ECO:0000250|UniProtKB:Q8K3E5, ECO:0000269|PubMed:21623382}.
• Disease: DISEASE: Joubert syndrome 3 (JBTS3) [MIM:608629]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 3 shows minimal extra central nervous system involvement and appears not to be associated with renal dysfunction. {ECO:0000269|PubMed:15322546, ECO:0000269|PubMed:15467982, ECO:0000269|PubMed:16155189, ECO:0000269|PubMed:16453322, ECO:0000269|PubMed:21623382, ECO:0000269|PubMed:23532844}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ectoderm Differentiation;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.998
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.07

Haploinsufficiency Scores

• pHI: 0.158
• hipred: N
• hipred_score: 0.172
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.207

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ahi1
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ahi1
• Affected structure: retinal cone cell
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: morphogenesis of a polarized epithelium;heart looping;positive regulation of receptor internalization;transmembrane receptor protein tyrosine kinase signaling pathway;central nervous system development;retina layer formation;vesicle-mediated transport;positive regulation of polarized epithelial cell differentiation;hindbrain development;cellular protein localization;cloaca development;photoreceptor cell outer segment organization;pronephric nephron tubule morphogenesis;pronephric duct morphogenesis;negative regulation of apoptotic process;positive regulation of transcription by RNA polymerase II;regulation of behavior;cilium assembly;specification of axis polarity;Kupffer's vesicle development;left/right axis specification;otic vesicle development;ciliary basal body-plasma membrane docking
• Cellular component: centrosome;centriole;cytosol;cell-cell junction;adherens junction;cilium;MKS complex;ciliary basal body;non-motile cilium
• Molecular function: protein binding;identical protein binding