Cone-rod dystrophy 19

Summary

Cone-rod dystrophy 19 (MONDO:0014372) is a disease caused by TTLL5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TTLL5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 19
Mondo ID	MONDO:0014372
OMIM	615860
DOID	DOID:0111025
UMLS	C4014501
MedGen	862938
GARD	0016022
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 19 · cone-rod dystrophy caused by mutation in TTLL5 · cone-rod dystrophy type 19 · CORD19 · TTLL5 cone-rod dystrophy

Data availability: 22 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › cone-rod dystrophy › cone-rod dystrophy 19

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

10 pathogenic, 5 uncertain significance, 3 benign, 1 likely pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071881	NM_015072.5(TTLL5):c.1166C>G (p.Ser389Ter)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
139513	NM_015072.5(TTLL5):c.1586_1589del (p.Glu529fs)	TTLL5	Pathogenic	criteria provided, single submitter
139514	NM_015072.5(TTLL5):c.401del (p.Leu134fs)	TTLL5	Pathogenic	criteria provided, single submitter
139515	NM_015072.5(TTLL5):c.3354G>A (p.Trp1118Ter)	TTLL5	Pathogenic	no assertion criteria provided
139516	NM_015072.5(TTLL5):c.1627G>T (p.Glu543Ter)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
139517	NM_015072.5(TTLL5):c.1627G>A (p.Glu543Lys)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
2693054	NM_015072.5(TTLL5):c.95G>A (p.Trp32Ter)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
2888538	NM_015072.5(TTLL5):c.2890C>T (p.Arg964Ter)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
522428	NM_015072.5(TTLL5):c.2782dup (p.Met928fs)	TTLL5	Pathogenic	no assertion criteria provided
845763	NM_015072.5(TTLL5):c.3177_3180del (p.Thr1059_Asn1060insTer)	TTLL5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
859370	NM_015072.5(TTLL5):c.2029C>T (p.Arg677Ter)	TTLL5	Pathogenic	criteria provided, multiple submitters, no conflicts
4849454	NM_015072.5(TTLL5):c.182-5_182-1delinsCTTAT	TTLL5	Likely pathogenic	criteria provided, single submitter
851210	NM_015072.5(TTLL5):c.1226G>A (p.Arg409Gln)	TTLL5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3463675	NM_015072.5(TTLL5):c.2269A>G (p.Ile757Val)	TTLL5	Uncertain significance	criteria provided, single submitter
4755415	NM_015072.5(TTLL5):c.419G>T (p.Arg140Leu)	TTLL5	Uncertain significance	criteria provided, single submitter
522427	NM_015072.5(TTLL5):c.987A>T (p.Glu329Asp)	TTLL5	Uncertain significance	criteria provided, single submitter
947701	NM_015072.5(TTLL5):c.3395G>A (p.Gly1132Glu)	TTLL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
948326	NM_015072.5(TTLL5):c.377A>C (p.Tyr126Ser)	TTLL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1164985	NM_015072.5(TTLL5):c.2603-4A>G	TTLL5	Benign	criteria provided, multiple submitters, no conflicts
677189	NM_015072.5(TTLL5):c.446C>T (p.Ala149Val)	TTLL5	Benign	criteria provided, multiple submitters, no conflicts
677191	NM_015072.5(TTLL5):c.1709-7T>C	TTLL5	Benign	criteria provided, multiple submitters, no conflicts
840444	NM_015072.5(TTLL5):c.1781A>G (p.Asp594Gly)	TTLL5	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TTLL5	Definitive	Autosomal recessive	cone-rod dystrophy 19	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TTLL5	Orphanet:1872	Cone rod dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TTLL5	HGNC:19963	ENSG00000119685	Q6EMB2	Tubulin polyglutamylase TTLL5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TTLL5	Tubulin polyglutamylase TTLL5	Polyglutamylase which modifies tubulin, generating polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TTLL5	Other/Unknown	no		TTL/TTLL_fam

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TTLL5	288	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTLL5	872

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTLL5	Q6EMB2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.004	TTLL5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sperm axoneme assembly	1	468.1×	0.004	TTLL5
retina development in camera-type eye	1	255.3×	0.004	TTLL5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TTLL5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TTLL5

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TTLL5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.