Microcephaly and chorioretinopathy 3
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Also known as MCCRP3microcephaly and chorioretinopathy caused by mutation in TUBGCP4microcephaly and chorioretinopathy type 3microcephaly and chorioretinopathy, autosomal recessive, 3microcephaly and chorioretinopathy, autosomal recessive, type 3TUBGCP4 microcephaly and chorioretinopathy
Summary
Microcephaly and chorioretinopathy 3 (MONDO:0014592) is a disease caused by TUBGCP4 (GenCC Strong), with 2 cohort genes.
At a glance
- Causal gene: TUBGCP4 (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 14
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | microcephaly and chorioretinopathy 3 |
| Mondo ID | MONDO:0014592 |
| OMIM | 616335 |
| DOID | DOID:0080107 |
| UMLS | C4225362 |
| MedGen | 902924 |
| GARD | 0018482 |
| Is cancer (heuristic) | no |
Also known as: MCCRP3 · microcephaly and chorioretinopathy caused by mutation in TUBGCP4 · microcephaly and chorioretinopathy type 3 · microcephaly and chorioretinopathy, autosomal recessive, 3 · microcephaly and chorioretinopathy, autosomal recessive, type 3 · TUBGCP4 microcephaly and chorioretinopathy
Data availability: 14 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › microcephaly › microcephaly and chorioretinopathy › microcephaly and chorioretinopathy 3
Related subtypes (2): microcephaly and chorioretinopathy 1, microcephaly and chorioretinopathy 2
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
14 retrieved; paginated sample, class counts are floors:
4 pathogenic/likely pathogenic, 4 pathogenic, 2 benign, 2 uncertain significance, 1 likely pathogenic, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 190123 | NM_014444.5(TUBGCP4):c.1746G>T (p.Leu582=) | TP53BP1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1029278 | NM_014444.5(TUBGCP4):c.889+2T>C | TUBGCP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1692991 | NM_014444.5(TUBGCP4):c.1669C>T (p.Arg557Ter) | TUBGCP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 190124 | NM_014444.5(TUBGCP4):c.579dup (p.Gly194fs) | TUBGCP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 190125 | NG_042168.2:g.(35752_37583)(39659?)del | TUBGCP4 | Pathogenic | no assertion criteria provided |
| 190126 | NM_014444.5(TUBGCP4):c.298del (p.Tyr100fs) | TUBGCP4 | Pathogenic | no assertion criteria provided |
| 803072 | NM_014444.5(TUBGCP4):c.1380G>A (p.Trp460Ter) | TUBGCP4 | Pathogenic | criteria provided, single submitter |
| 982788 | NM_014444.5(TUBGCP4):c.778C>T (p.Arg260Ter) | TUBGCP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1299230 | NM_014444.5(TUBGCP4):c.346del (p.His116fs) | TUBGCP4 | Likely pathogenic | criteria provided, single submitter |
| 1520885 | NM_014444.5(TUBGCP4):c.1597-11A>G | TUBGCP4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 377341 | NM_014444.5(TUBGCP4):c.998G>A (p.Arg333His) | TUBGCP4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1165270 | NM_014444.5(TUBGCP4):c.1014+15G>A | TUBGCP4 | Benign | criteria provided, multiple submitters, no conflicts |
| 1226213 | NM_014444.5(TUBGCP4):c.1280-24T>C | TUBGCP4 | Benign | criteria provided, multiple submitters, no conflicts |
| 741414 | NM_014444.5(TUBGCP4):c.1781C>T (p.Ser594Leu) | TUBGCP4 | Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · 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 |
|---|---|---|---|---|
| TUBGCP4 | Strong | Autosomal recessive | microcephaly and chorioretinopathy 3 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TUBGCP4 | Orphanet:2518 | Autosomal recessive chorioretinopathy-microcephaly syndrome |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TUBGCP4 | HGNC:16691 | ENSG00000137822 | Q9UGJ1 | Gamma-tubulin complex component 4 | gencc,clinvar |
| TP53BP1 | HGNC:11999 | ENSG00000067369 | Q12888 | TP53-binding protein 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TUBGCP4 | Gamma-tubulin complex component 4 | Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation. |
| TP53BP1 | TP53-binding protein 1 | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 2 · 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 | 2 | 1.8× | 0.312 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TUBGCP4 | Other/Unknown | no | GCP, GCP_C, GCP_N | |
| TP53BP1 | Other/Unknown | no | BRCT_dom, Rib_uL2_dom2, 53-BP1_Tudor |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ cell | 1 |
| secondary oocyte | 1 |
| sperm | 1 |
| adenohypophysis | 1 |
| adrenal tissue | 1 |
| pituitary gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TUBGCP4 | 259 | ubiquitous | marker | sperm, secondary oocyte, male germ cell |
| TP53BP1 | 285 | ubiquitous | marker | pituitary gland, adenohypophysis, adrenal tissue |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TP53BP1 | 4,411 |
| TUBGCP4 | 1,322 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TP53BP1 | Q12888 | 45 |
| TUBGCP4 | Q9UGJ1 | 28 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| SUMOylation of transcription factors | 1 | 285.5× | 0.017 | TP53BP1 |
| Nonhomologous End-Joining (NHEJ) | 1 | 84.0× | 0.017 | TP53BP1 |
| Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | 1 | 73.2× | 0.017 | TP53BP1 |
| Recruitment of mitotic centrosome proteins and complexes | 1 | 68.0× | 0.017 | TUBGCP4 |
| G2/M DNA damage checkpoint | 1 | 60.1× | 0.017 | TP53BP1 |
| Recruitment of NuMA to mitotic centrosomes | 1 | 58.3× | 0.017 | TUBGCP4 |
| Processing of DNA double-strand break ends | 1 | 57.1× | 0.017 | TP53BP1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator | 1 | 1404.3× | 0.007 | TP53BP1 |
| cellular response to X-ray | 1 | 842.6× | 0.007 | TP53BP1 |
| double-strand break repair via classical nonhomologous end joining | 1 | 842.6× | 0.007 | TP53BP1 |
| positive regulation of isotype switching | 1 | 648.1× | 0.007 | TP53BP1 |
| protein localization to site of double-strand break | 1 | 526.6× | 0.007 | TP53BP1 |
| microtubule nucleation | 1 | 312.1× | 0.008 | TUBGCP4 |
| negative regulation of double-strand break repair via homologous recombination | 1 | 312.1× | 0.008 | TP53BP1 |
| spindle assembly | 1 | 221.7× | 0.009 | TUBGCP4 |
| double-strand break repair via nonhomologous end joining | 1 | 210.7× | 0.009 | TP53BP1 |
| DNA damage checkpoint signaling | 1 | 195.9× | 0.009 | TP53BP1 |
| cytoplasmic microtubule organization | 1 | 172.0× | 0.010 | TUBGCP4 |
| meiotic cell cycle | 1 | 122.1× | 0.012 | TUBGCP4 |
| mitotic cell cycle | 1 | 66.9× | 0.021 | TUBGCP4 |
| protein homooligomerization | 1 | 61.1× | 0.021 | TP53BP1 |
| protein-containing complex assembly | 1 | 56.9× | 0.021 | TUBGCP4 |
| DNA damage response | 1 | 26.8× | 0.042 | TP53BP1 |
| positive regulation of DNA-templated transcription | 1 | 14.0× | 0.074 | TP53BP1 |
| positive regulation of transcription by RNA polymerase II | 1 | 7.4× | 0.130 | TP53BP1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TUBGCP4 | 0 | 0 |
| TP53BP1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TP53BP1 | 24 | Binding:24 |
| TUBGCP4 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | 2 | TUBGCP4, TP53BP1 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TUBGCP4 | 1 | — |
| TP53BP1 | 24 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.