KIAA0586

KIAA0586

Basic information

Region (hg38): 14:58427384-58551297

Links

ENSG00000100578 ∙ NCBI:9786 ∙ OMIM:610178 ∙ HGNC:19960 ∙ Uniprot:Q9BVV6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 17 (Definitive), mode of inheritance: AR
• short-rib thoracic dysplasia 14 with polydactyly (Strong), mode of inheritance: AR
• Joubert syndrome 23 (Strong), mode of inheritance: AR
• short-rib thoracic dysplasia 14 with polydactyly (Moderate), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with Jeune asphyxiating thoracic dystrophy (Supportive), mode of inheritance: AR
• Joubert syndrome 23 (Definitive), mode of inheritance: AR
• Joubert syndrome 23 (Strong), mode of inheritance: AR
• short-rib thoracic dysplasia 14 with polydactyly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 23; Short rib thoracic dysplasia 14 with polydactyly	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	26096313; 26166481; 26386044

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KIAA0586 gene.

• Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly (836 variants)
• not provided (255 variants)
• Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23 (191 variants)
• Inborn genetic diseases (78 variants)
• Joubert syndrome 23 (38 variants)
• Short-rib thoracic dysplasia 14 with polydactyly (11 variants)
• KIAA0586-related condition (10 variants)
• not specified (9 variants)
• Joubert syndrome and related disorders (5 variants)
• Neurodevelopmental disorder (2 variants)
• Retinal dystrophy (2 variants)
• Congenital cerebellar hypoplasia;Rod-cone dystrophy;Intellectual disability (1 variants)
• Familial aplasia of the vermis (1 variants)
• Jeune thoracic dystrophy (1 variants)
• Intellectual disability;Congenital cerebellar hypoplasia;Rod-cone dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIAA0586 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		12	175	7	195
missense	1	2	533	21	8	565
nonsense	25	4	1			30
start loss			3		1	4
frameshift	34	9	2			45
inframe indel			8			8
splice donor/acceptor (+/-2bp)	2	16	2			20
splice region	2		32	31	7	72
non coding	4	2	33	159	63	261
Total	67	33	594	355	79

Highest pathogenic variant AF is 0.0000854

Variants in KIAA0586

This is a list of pathogenic ClinVar variants found in the KIAA0586 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-58427629-A-G		not specified	Uncertain significance (May 12, 2022)
14-58427631-G-A		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Jan 01, 2024)
14-58427632-T-C		Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23	Uncertain significance (Apr 11, 2021)
14-58427633-T-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Aug 21, 2023)
14-58427638-G-A		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Conflicting classifications of pathogenicity (Nov 01, 2022)
14-58427641-A-C		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Dec 08, 2021)
14-58427642-G-C		Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23	Uncertain significance (Oct 13, 2022)
14-58427647-T-C		KIAA0586-related disorder	Uncertain significance (Jan 29, 2024)
14-58427649-G-C		Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23	Likely benign (Jun 26, 2022)
14-58427651-C-T		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Likely benign (Oct 28, 2023)
14-58427653-C-T		Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23	Likely benign (Mar 19, 2022)
14-58427859-T-C			Benign (Jul 06, 2018)
14-58428196-C-T			Likely benign (Jul 21, 2018)
14-58428218-A-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Likely benign (Feb 22, 2022)
14-58428228-C-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Likely benign (Jul 13, 2023)
14-58428229-G-A		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Likely benign (Nov 17, 2023)
14-58428232-C-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Nov 26, 2021)
14-58428234-T-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly • KIAA0586-related disorder	Likely benign (Jan 15, 2024)
14-58428236-A-C		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Likely pathogenic (Jun 21, 2023)
14-58428237-G-A		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Dec 07, 2023)
14-58428245-C-T		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Jan 05, 2022)
14-58428260-A-G			Uncertain significance (Feb 01, 2021)
14-58428261-C-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Nov 01, 2022)
14-58428263-A-G		Joubert syndrome 23;Short-rib thoracic dysplasia 14 with polydactyly	Uncertain significance (Sep 05, 2023)
14-58428264-T-C		Short-rib thoracic dysplasia 14 with polydactyly;Joubert syndrome 23	Likely benign (May 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KIAA0586	protein_coding	protein_coding	ENST00000354386	34	121114

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.13e-16	1.00	123905	1	747	124653	0.00300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.371	735	764	0.962	0.0000362	10687
Missense in Polyphen		246	233.53	1.0534		3362
Synonymous	-0.0283	267	266	1.00	0.0000135	3085
Loss of Function	3.44	36	66.2	0.544	0.00000297	1006

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00433	0.00421
Ashkenazi Jewish	0.00838	0.00748
East Asian	0.000431	0.000389
Finnish	0.000806	0.000789
European (Non-Finnish)	0.00498	0.00457
Middle Eastern	0.000431	0.000389
South Asian	0.000892	0.000785
Other	0.00267	0.00232

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for ciliogenesis and sonic hedgehog/SHH signaling. Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1. May play a role in early ciliogenesis in the disappearance of centriolar satellites that preceeds ciliary vesicle formation (PubMed:24421332). Involved in regulation of cell intracellular organization. Involved in regulation of cell polarity (By similarity). Required for asymmetrical localization of CEP120 to daughter centrioles (By similarity). {ECO:0000250|UniProtKB:E9PV87, ECO:0000250|UniProtKB:Q1G7G9, ECO:0000269|PubMed:24421332}.
• Disease: DISEASE: Joubert syndrome 23 (JBTS23) [MIM:616490]: A mild form of Joubert syndrome, 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, renal disease, liver fibrosis, and polydactyly. {ECO:0000269|PubMed:26026149, ECO:0000269|PubMed:26096313, ECO:0000269|PubMed:26386044, ECO:0000269|PubMed:26386247, ECO:0000269|PubMed:26429889}. Note=The disease is caused by mutations affecting the gene represented in this entry. Some patients with biallelic KIAA0586 mutations manifest a disease phenotype with features of Joubert syndrome and additional findings of a small thorax and respiratory problems consistent with Jeune syndrome (Joubert-Jeune ciliopathy). {ECO:0000269|PubMed:26386044}.; DISEASE: Short-rib thoracic dysplasia 14 with polydactyly (SRTD14) [MIM:616546]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:26166481}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0940

Intolerance Scores

• loftool: 0.978
• rvis_EVS: 0.61
• rvis_percentile_EVS: 82.97

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.145
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.365

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: 2700049A03Rik
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; limbs/digits/tail 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); skeleton phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: si:ch211-185a18.2
• Affected structure: eye photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: smoothened signaling pathway;cilium assembly;regulation of establishment of protein localization
• Cellular component: photoreceptor inner segment;centrosome;centriole;ciliary basal body