BBS4 Bardet-Biedl syndrome 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BBS4provided by HGNC
Official Full Name: Bardet-Biedl syndrome 4provided by HGNC
Primary source: HGNC:HGNC:969
See related: Ensembl:ENSG00000140463 MIM:600374; AllianceGenome:HGNC:969
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse. The similar phenotypes exhibited by mutations in BBS gene family members are likely due to the protein's shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene has sequence similarity to O-linked N-acetylglucosamine (O-GlcNAc) transferases in plants and archaebacteria and in human forms a multi-protein "BBSome" complex with seven other BBS proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in testis (RPKM 12.7), prostate (RPKM 9.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q24.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (72686207..72738473)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (70503538..70555769)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (72978548..73030814)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation.
Title: Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation.
BBS4 protein has basal body/ciliary localization in sensory organs but extra-ciliary localization in oligodendrocytes during human development.
Title: BBS4 protein has basal body/ciliary localization in sensory organs but extra-ciliary localization in oligodendrocytes during human development.
BBS4 Is Essential for Nuclear Transport of Transcription Factors Mediating Neuronal ER Stress Response.
Title: BBS4 Is Essential for Nuclear Transport of Transcription Factors Mediating Neuronal ER Stress Response.
The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells.
Title: The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells.
a novel nonsense mutation in BBS4 gene in a Chinese family with Bardet-Biedl syndrome. This homozygous mutation was predicted to completely abolish the synthesis of the BBS4 protein; a rare heterozygous missense SNP in BBS10 gene was also detected
Title: A novel nonsense mutation in BBS4 gene identified in a Chinese family with Bardet-Biedl syndrome.
Results present evidence of a role for BBS4 in mediating the phosphorylation of TrkB by BDNF and its activation requires a proper localization to the ciliary axoneme.
Title: BBS4 is necessary for ciliary localization of TrkB receptor and activation by BDNF.
mediates endosomal recycling, sorting and signal transduction of Notch receptors
Title: Basal body proteins regulate Notch signaling through endosomal trafficking.
loss of BBS1, BBS4, or OFD1 led to decreased NF-kappaB activity and concomitant IkappaBbeta accumulation and that these defects were ameliorated with SFN treatment.
Title: Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators.
Findings indicate that Bbs proteins play a central role in the regulation of the actin cytoskeleton and control the cilia length through alteration of RhoA levels.
Title: Bardet-Biedl syndrome proteins control the cilia length through regulation of actin polymerization.
Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice.
Title: Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Bardet-Biedl syndrome MedGen: C0752166 GeneReviews: Bardet-Biedl Syndrome Overview	Compare labs
Bardet-Biedl syndrome 4 MedGen: C2936864 OMIM: 615982 GeneReviews: Bardet-Biedl Syndrome Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D15S1270 (e-PCR)
- UniSTS:81787

RH103709 (e-PCR)
- UniSTS:98034

Homology

Homologs of the BBS4 gene: The BBS4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, and frog.
Orthologs from Annotation Pipeline: 494 organisms have orthologs with human gene BBS4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables alpha-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables beta-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables dynactin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in adult behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in brain morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in centrosome cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cerebral cortex development	ISS Inferred from Sequence or Structural Similarity more info
involved_in cilium assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cilium assembly	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cilium assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in dendrite development	ISS Inferred from Sequence or Structural Similarity more info
involved_in face development	IEA Inferred from Electronic Annotation more info
involved_in fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in fat pad development	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in heart looping	ISS Inferred from Sequence or Structural Similarity more info
involved_in hippocampus development	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular transport	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in maintenance of protein location in nucleus	IGI Inferred from Genetic Interaction more info	PubMed
involved_in melanosome transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in microtubule anchoring at centrosome	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microtubule cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitotic cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of GTPase activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of appetite by leptin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of systemic arterial blood pressure	IEA Inferred from Electronic Annotation more info
involved_in neural tube closure	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in non-motile cilium assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoreceptor cell maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoreceptor cell outer segment organization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cilium assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in protein localization to centrosome	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to cilium	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in protein localization to cilium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to organelle	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to photoreceptor outer segment	IEA Inferred from Electronic Annotation more info
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of cilium beat frequency involved in ciliary motility	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lipid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of non-motile cilium assembly	IEA Inferred from Electronic Annotation more info
involved_in regulation of stress fiber assembly	IEA Inferred from Electronic Annotation more info
involved_in retina homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in retinal rod cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in sensory perception of smell	ISS Inferred from Sequence or Structural Similarity more info
involved_in sensory processing	TAS Traceable Author Statement more info	PubMed
involved_in social behavior	IEA Inferred from Electronic Annotation more info
involved_in spermatid development	ISS Inferred from Sequence or Structural Similarity more info
involved_in striatum development	ISS Inferred from Sequence or Structural Similarity more info
involved_in ventricular system development	IEA Inferred from Electronic Annotation more info
involved_in visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of BBSome	IDA Inferred from Direct Assay more info	PubMed
part_of BBSome	IPI Inferred from Physical Interaction more info	PubMed
located_in centriolar satellite	IDA Inferred from Direct Assay more info	PubMed
located_in centriole	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in ciliary basal body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in ciliary basal body	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary membrane	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary transition zone	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in motile cilium	IDA Inferred from Direct Assay more info	PubMed
located_in non-motile cilium	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in pericentriolar material	IDA Inferred from Direct Assay more info	PubMed
located_in photoreceptor connecting cilium	IEA Inferred from Electronic Annotation more info
located_in photoreceptor inner segment	IEA Inferred from Electronic Annotation more info
located_in photoreceptor outer segment	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: Bardet-Biedl syndrome 4 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009416.3 RefSeqGene

Range

5002..57268

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001252678.2 → NP_001239607.1 Bardet-Biedl syndrome 4 protein isoform 2

See identical proteins and their annotated locations for NP_001239607.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal exon and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC009712

Consensus CDS

CCDS58377.1

UniProtKB/Swiss-Prot

Q96RK4

Related

ENSP00000378631.3, ENST00000395205.6

Conserved Domains (2) summary

sd00006
Location:98 → 126

TPR; TPR repeat [structural motif]

cl26002
Location:1 → 221

TPR_11; TPR repeat
NM_001320665.2 → NP_001307594.1 Bardet-Biedl syndrome 4 protein isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an exon in the 3' coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AC009712

UniProtKB/Swiss-Prot

Q96RK4

Conserved Domains (3) summary

smart00028
Location:170 → 201

TPR; Tetratricopeptide repeats

COG0457
Location:46 → 321

TPR; Tetratricopeptide (TPR) repeat [General function prediction only]

sd00006
Location:101 → 129

TPR; TPR repeat [structural motif]
NM_033028.5 → NP_149017.2 Bardet-Biedl syndrome 4 protein isoform 1

See identical proteins and their annotated locations for NP_149017.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC009712

Consensus CDS

CCDS10246.1

UniProtKB/Swiss-Prot

Q96H45, Q96RK4

UniProtKB/TrEMBL

A0A0S2Z3A9

Related

ENSP00000268057.4, ENST00000268057.9

Conserved Domains (2) summary

sd00006
Location:101 → 129

TPR; TPR repeat [structural motif]

cl26002
Location:18 → 400

TPR_11; TPR repeat

RNA

NR_045565.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC009712
NR_045566.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC009712

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

72686207..72738473

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047432911.1 → XP_047288867.1 Bardet-Biedl syndrome 4 protein isoform X1
XM_017022450.2 → XP_016877939.1 Bardet-Biedl syndrome 4 protein isoform X2
XM_047432912.1 → XP_047288868.1 Bardet-Biedl syndrome 4 protein isoform X3
XM_017022454.2 → XP_016877943.1 Bardet-Biedl syndrome 4 protein isoform X3

UniProtKB/Swiss-Prot

Q96RK4

Conserved Domains (2) summary

sd00006
Location:98 → 126

TPR; TPR repeat [structural motif]

cl26002
Location:1 → 221

TPR_11; TPR repeat
XM_047432913.1 → XP_047288869.1 Bardet-Biedl syndrome 4 protein isoform X3
XM_047432914.1 → XP_047288870.1 Bardet-Biedl syndrome 4 protein isoform X4