B9D2 (B9 domain containing 2)

Gene

• Entrez ID: 80776
• Gene name: B9 domain containing 2
• Gene symbol: B9D2
• Synonyms (NCBI Gene): ICIS-1, JBTS34, MKS10, MKSR-2, MKSR2
• Chromosome: 19
• Chromosome location: 19q13.2
• Summary: This gene encodes a B9 domain protein, which are exclusively found in ciliated organisms. The gene is upregulated during mucociliary differentiation, and the encoded protein localizes to basal bodies and cilia. Disrupting expression of this gene results i

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs757863670	A>G	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs786204189	ATGTCCCC>-	Likely-pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant, initiator codon variant
rs1568484575	G>C	Likely-pathogenic	Coding sequence variant, stop gained

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	21602787, 26638075, 27173435, 32296183, 32726168, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IDA	19208769
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005929	Component	Cilium	IEA
GO:0016020	Component	Membrane	IEA
GO:0030030	Process	Cell projection organization	IEA
GO:0036038	Component	MKS complex	IBA
GO:0036038	Component	MKS complex	IEA
GO:0036038	Component	MKS complex	ISS
GO:0036064	Component	Ciliary basal body	IDA	19208769
GO:0042995	Component	Cell projection	IEA
GO:0043015	Function	Gamma-tubulin binding	IEA
GO:0043015	Function	Gamma-tubulin binding	ISS
GO:0060271	Process	Cilium assembly	IBA
GO:0060271	Process	Cilium assembly	IEA
GO:0060271	Process	Cilium assembly	ISS

Other IDs

• MIM: 611951
• HGNC: 28636
• e!Ensembl: ENSG00000123810

Protein

• UniProt ID: Q9BPU9
• Protein name: B9 domain-containing protein 2 (MKS1-related protein 2)
• Protein 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07162	B9-C2	4 → 164	Ciliary basal body-associated, B9 protein	Domain

• Sequence:

  MAEVHVIGQIIGASGFSESSLFCKWGIHTGAAWKLLSGVREGQTQVDTPQIGDMAYWSHP
  IDLHFATKGLQGWPRLHFQVWSQDSFGRCQLAGYGFCHVPSSPGTHQLACPTWRPLGSWR
  EQLARAFVGGGPQLLHGDTIYSGADRYRLHTAAGGTVHLEIGLLLRNFDRYGVEC

• Sequence length: 175

Pathways

Reactome:

Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
Separation of Sister Chromatids
Resolution of Sister Chromatid Cohesion
Anchoring of the basal body to the plasma membrane
RHO GTPases Activate Formins
Mitotic Prometaphase
EML4 and NUDC in mitotic spindle formation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Joubert syndrome	Likely pathogenic; Pathogenic	rs786204189, rs750436680, rs863225150, rs757863670	RCV000168253 RCV000201776 RCV000201694 RCV000201607	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Joubert syndrome 34	Likely pathogenic; Pathogenic	rs750436680, rs863225150, rs757863670	RCV002265681 RCV002265683 RCV002265682	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Joubert syndrome and related disorders	Likely pathogenic; Pathogenic	rs750436680, rs863225150, rs2513398193, rs2513408240, rs1487082103	RCV001844085 RCV001844086 RCV003226859 RCV003226860 RCV003330400	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Meckel syndrome, type 10	Pathogenic; Likely pathogenic	rs1487082103, rs1388769907, rs1568484575	RCV000023919 RCV000993853 RCV001002781	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meckel-Gruber syndrome	Likely pathogenic; Pathogenic	rs786204189	RCV001850379	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
B9D2-related disorder	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliopathy	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar CTD, ClinGen	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONGENITAL ABSENCE OF PART OF BRAIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HYPOPLASIA OF PART OF BRAIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL APLASIA OF THE VERMIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYDRANENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ISOLATED JOUBERT SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LISSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MACROGYRIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MECKEL SYNDROME	—	CTD, Orphanet CTD, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROGYRIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anencephaly	Anencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anophthalmos	Syndromic microphthalmia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG	21763481, 26092869		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Carcinoma	Colorectal Cancer	GWASDB_DG	24836286		★☆☆☆☆ Found in Text Mining only
Congenital absence of spleen	Asplenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital cerebral hernia	Congenital Cerebral Hernia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystic liver disease	Cystic liver disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Double ureter	Double Ureter	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial aplasia of the vermis	Cerebellar vermis agenesis	GENOMICS_ENGLAND_DG	21763481, 26092869		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial aplasia of the vermis	Cerebellar vermis agenesis	BEFREE	26092869		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial aplasia of the vermis	Cerebellar vermis agenesis	CLINVAR_DG	26092869		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fibrosis of pancreas	Fibrosis Of Pancreas	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hepatic Fibrosis, Congenital	Congenital Hepatic Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lobar Holoprosencephaly	Lobar Holoprosencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Meckel syndrome	Meckel Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Meckel syndrome type 1	Meckel Syndrome	BEFREE	21763481, 31411728		★☆☆☆☆ Found in Text Mining only
Meckel syndrome type 1	Meckel Syndrome	GENOMICS_ENGLAND_DG	21763481, 26092869		★☆☆☆☆ Found in Text Mining only
MECKEL SYNDROME, TYPE 10	Meckel Syndrome	GENOMICS_ENGLAND_DG	21763481, 26092869		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MECKEL SYNDROME, TYPE 10	Meckel Syndrome	UNIPROT_DG	21763481, 26092869		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Meckel-Gruber syndrome	Meckel-Gruber Syndrome	ORPHANET_DG	21763481		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcornea	Microcornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multicystic Dysplastic Kidney	Multicystic renal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Occipital Encephalocele	Occipital Encephalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic Cyst	Pancreatic Cyst	HPO_DG			★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polycystic liver disease	Polycystic liver disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG	26092869		★☆☆☆☆ Found in Text Mining only
Polydactyly preaxial type 1	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Postaxial foot polydactyly	Foot Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sclerocornea	Sclerocornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Simple renal cyst	Renal cyst	HPO_DG			★☆☆☆☆ Found in Text Mining only
Situs inversus totalis	Situs Inversus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Talipes	Talipes	HPO_DG			★☆☆☆☆ Found in Text Mining only
True Hermaphroditism (disorder)	True Hermaphroditism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ulnar polydactyly of fingers	Postaxial hand polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Urethral atresia	Urethral atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only