GeneBe

TUB

protein-coding

TUB bipartite transcription factor

Gene summary

This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_177972.3

Inheritance

AR, AD

ClinVar variants

P:22U:298B:172

Top phenotype

Retinal dystrophy and obesity

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr11:8,019,244-8,106,243

External References & Databases

Ensembl (ENSG00000166402)NCBI Gene (7275)OMIM (601197)HGNC:12406GenCCUniProt (P50607)AlphaFoldClinVar (TUB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~87.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinal dystrophy and obesityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014522

Submitter: PanelApp Australia

retinal dystrophy and obesityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014522

Submitter: G2P

essential tremorLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0003233

Submitter: Ambry Genetics

retinal dystrophy and obesitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014522

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

retinal dystrophy and obesityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014522

Submitter: Ambry Genetics

retinal dystrophy and obesityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014522

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Retinal dystrophy and obesityAR

Manifestation: Endocrine; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 24375934Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUB variants in ClinVar

5 Conditions Cataloged
not providedTotal: 457
TUB-related disorderTotal: 304
not specifiedTotal: 150
Retinal dystrophy and obesityTotal: 20
Retinal dystrophyTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177972.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
154
clinvar
2
clinvar
 162
missense
283
clinvar
14
clinvar
 297
nonsense
2
clinvar
1
clinvar
1
clinvar
 4
start loss
1
clinvar
 1
frameshift
2
clinvar
6
clinvar
5
clinvar
1
clinvar
 14
splice donor/acceptor (+/-2bp)
11
clinvar
2
clinvar
1
clinvar
 14
Total4182981702492

Highest pathogenic variant AF is 0.00003903573

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_177972.3RefSeqNP_813977.112MANE Select
ENST00000299506.3EnsemblENSP00000299506.312MANE Select
NM_001440538.1RefSeqNP_001427467.112Standard
NM_001440539.1RefSeqNP_001427468.112Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • g-protein signaling through tubby proteins

Biological Process

  • phagocytosis, recognition
  • sensory perception of sound
  • response to hormone
  • photoreceptor cell maintenance
  • positive regulation of phagocytosis

Molecular Function

  • phosphatidylinositol binding
  • protein-containing complex binding

Cellular Component

  • extracellular region
  • nucleus
  • cytoplasm
  • cytosol
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000305253
Coding exons
13
Length
86869
Individuals with no LoFs
125714
Homozygous LoFs
0
Heterozygous LoFs
33
Defined
125747
p
0.000131
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4703313560.9300.00002273655
Missense (PolyPhen)135165.290.816761697
Synonymous-1.481571351.160.000008411109
Loss of Function3.411030.20.3310.00000175326

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.000230.00023rare
Ashkenazi Jewish0.000100.000099rare
East Asian00.0absent
Finnish0.000140.000092rare
European (Non-Finnish)0.000110.00011rare
South Asian0.000170.00016rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Functions in signal transduction from heterotrimeric G protein-coupled receptors. Binds to membranes containing phosphatidylinositol 4,5-bisphosphate. Can bind DNA (in vitro). May contribute to the regulation of transcription in the nucleus. Could be involved in the hypothalamic regulation of body weight (By similarity). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages. {ECO:0000250, ECO:0000269|PubMed:19837063}.;
Disease
DISEASE: Retinal dystrophy and obesity (RDOB) [MIM:616188]: A disease characterized by obesity, night blindness, decreased visual acuity, and electrophysiological features of a rod cone dystrophy. {ECO:0000269|PubMed:24375934}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.253

Intolerance Scores

LoFtool
0.0654
RVIS EVS
-0.91
RVIS percentile EVS
10.12

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.726

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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