GeneBe

TTLL5

tubulin tyrosine ligase like 5, the group of Tubulin tyrosine ligase family

Basic information

Region (hg38): 14:75633625-75955079

Previous symbols: [ "KIAA0998" ]

Links

ENSG00000119685 ∙ NCBI:23093 ∙ OMIM:612268 ∙ HGNC:19963 ∙ Uniprot:Q6EMB2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • cone-rod dystrophy 19 (Strong), mode of inheritance: AR
  • cone-rod dystrophy (Supportive), mode of inheritance: AD
  • cone-rod dystrophy 19 (Moderate), mode of inheritance: AR
  • cone-rod dystrophy 19 (Definitive), mode of inheritance: AR
  • inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cone-rod dystrophy 19ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingOphthalmologic24791901

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTLL5 gene.

  • not_provided (933 variants)
  • Inborn_genetic_diseases (179 variants)
  • Retinal_dystrophy (31 variants)
  • TTLL5-related_disorder (22 variants)
  • Cone-rod_dystrophy_19 (16 variants)
  • not_specified (6 variants)
  • Cone-rod_dystrophy (5 variants)
  • Retinitis_pigmentosa (3 variants)
  • Abnormal_sperm_morphology (1 variants)
  • Optic_atrophy (1 variants)
  • Oligospermia (1 variants)
  • Central_areolar_choroidal_dystrophy (1 variants)
  • Reduced_sperm_motility (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTLL5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015072.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
208
clinvar
7
clinvar
 221
missense
1
clinvar
3
clinvar
493
clinvar
20
clinvar
4
clinvar
 521
nonsense
24
clinvar
9
clinvar
 33
start loss
0
frameshift
35
clinvar
5
clinvar
 40
splice donor/acceptor (+/-2bp)
6
clinvar
15
clinvar
1
clinvar
1
clinvar
 23
Total 66 32 500 228 12

Highest pathogenic variant AF is 0.000133199

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TTLL5protein_codingprotein_codingENST00000298832 31321454
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.92e-220.99912551122351257480.000943
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.04007257221.000.00004048371
Missense in Polyphen140160.740.870991870
Synonymous0.3042522580.9760.00001382478
Loss of Function3.374880.60.5950.00000495841

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002230.00222
Ashkenazi Jewish0.000.00
East Asian0.003870.00349
Finnish0.0003230.000323
European (Non-Finnish)0.0007080.000703
Middle Eastern0.003870.00349
South Asian0.001120.00111
Other0.001140.00114

dbNSFP

Source: dbNSFP

Function
FUNCTION: Polyglutamylase which preferentially modifies alpha- tubulin. Involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step (By similarity). Required for CCSAP localization to both spindle and cilia microtubules. Increases the effects of NCOA2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (PubMed:17116691, PubMed:22493317). {ECO:0000250|UniProtKB:Q8CHB8, ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:22493317}.;
Disease
DISEASE: Cone-rod dystrophy 19 (CORD19) [MIM:615860]: A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:24791901}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Intolerance Scores

loftool
0.959
rvis_EVS
-0.92
rvis_percentile_EVS
9.83

Haploinsufficiency Scores

pHI
0.606
hipred
N
hipred_score
0.426
ghis
0.555

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.704

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Ttll5
Phenotype
reproductive system phenotype; cellular phenotype;

Gene ontology

Biological process
protein polyglutamylation;retina development in camera-type eye
Cellular component
nucleus;centrosome;cytosol;microtubule;plasma membrane;cilium
Molecular function
ATP binding;tubulin-glutamic acid ligase activity