B9D1

B9 domain containing 1, the group of MicroRNA protein coding host genes|MKS complex|B9 domain containing

Basic information

Region (hg38): 17:19334307-19378193

Links

ENSG00000108641 ∙ NCBI:27077 ∙ OMIM:614144 ∙ HGNC:24123 ∙ Uniprot:Q9UPM9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meckel syndrome, type 9 (Strong), mode of inheritance: AR
• Meckel syndrome, type 9 (Moderate), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome 27 (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 27; Meckel syndrome 9	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; Genitourinary; Musculoskeletal; Neurologic; Renal	21493627; 24886560

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B9D1 gene.

• Familial aplasia of the vermis;Meckel-Gruber syndrome (70 variants)
• Meckel-Gruber syndrome;Familial aplasia of the vermis (66 variants)
• not provided (42 variants)
• Meckel syndrome, type 9 (21 variants)
• not specified (15 variants)
• Joubert syndrome 27 (13 variants)
• Inborn genetic diseases (11 variants)
• Familial aplasia of the vermis (3 variants)
• B9D1-related condition (1 variants)
• B9D1-Related Disorders (1 variants)
• Joubert syndrome and related disorders (1 variants)
• Intellectual disability (1 variants)
• Jeune thoracic dystrophy (1 variants)
• Meckel-Gruber syndrome (1 variants)
• Meckel syndrome, type 9;Joubert syndrome 27 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B9D1 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	31		32
missense	1	3	69	2		75
nonsense	1		2			3
start loss						0
frameshift	1		2			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	2		3
non coding			10	36	18	64
Total	4	4	86	69	18

Highest pathogenic variant AF is 0.0000132

Variants in B9D1

This is a list of pathogenic ClinVar variants found in the B9D1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-19337659-G-A		Joubert syndrome 27 • Meckel syndrome, type 9	Benign (Jul 14, 2021)
17-19337659-G-C			Likely benign (Jul 21, 2018)
17-19337684-C-A			Benign (Jul 31, 2018)
17-19337728-G-T		Intellectual disability	Uncertain significance (Mar 02, 2020)
17-19337749-C-G		Joubert syndrome 27 • not specified • B9D1-related disorder	Conflicting classifications of pathogenicity (Dec 18, 2023)
17-19337782-A-G			Benign (Jul 06, 2018)
17-19337906-T-C			Likely benign (Aug 14, 2018)
17-19337913-T-C			Benign (Jun 26, 2018)
17-19338043-A-G			Benign (Jun 19, 2018)
17-19338052-C-T			Likely benign (Oct 09, 2018)
17-19341269-G-A		B9D1-related disorder	Benign/Likely benign (Feb 01, 2024)
17-19343131-G-T			Likely benign (Feb 28, 2019)
17-19343261-C-T		Meckel syndrome, type 9	Uncertain significance (Jan 13, 2018)
17-19343272-G-A		Meckel syndrome, type 9	Uncertain significance (Jan 13, 2018)
17-19343317-C-T			Likely benign (Aug 24, 2017)
17-19343321-A-G		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Mar 10, 2021)
17-19343322-C-A		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Sep 11, 2023)
17-19343326-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (May 12, 2022)
17-19343331-G-T		Meckel-Gruber syndrome;Familial aplasia of the vermis • Inborn genetic diseases	Uncertain significance (Mar 28, 2023)
17-19343332-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome • Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
17-19343337-G-C		Meckel syndrome, type 9 • Meckel-Gruber syndrome;Familial aplasia of the vermis	Conflicting classifications of pathogenicity (Jan 07, 2021)
17-19343350-C-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Mar 11, 2022)
17-19343354-A-G		not specified • Meckel syndrome, type 9 • Familial aplasia of the vermis;Meckel-Gruber syndrome	Benign/Likely benign (Jan 30, 2024)
17-19343355-C-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Mar 04, 2022)
17-19343357-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Sep 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B9D1	protein_coding	protein_coding	ENST00000261499	7	40629

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00280	0.945	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.102	121	124	0.974	0.00000783	1325
Missense in Polyphen		30	34.66	0.86555		344
Synonymous	-0.582	53	47.9	1.11	0.00000319	393
Loss of Function	1.69	6	12.4	0.482	6.06e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity). {ECO:0000250}.
• Disease: DISEASE: Meckel syndrome 9 (MKS9) [MIM:614209]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:21493627}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 27 (JBTS27) [MIM:617120]: A 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. JBTS27 inheritance is autosomal recessive. {ECO:0000269|PubMed:24886560}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.551
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.100
• hipred: N
• hipred_score: 0.267
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.270

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: B9d1
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo 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); vision/eye 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); digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: in utero embryonic development;vasculature development;smoothened signaling pathway;regulation of protein localization;embryonic digit morphogenesis;camera-type eye development;cilium assembly;neuroepithelial cell differentiation;ciliary basal body-plasma membrane docking
• Cellular component: centrosome;cytosol;membrane;ciliary transition zone;MKS complex;ciliary basal body
• Molecular function: hedgehog receptor activity