Branchiootorenal syndrome 2
diseaseOn this page
Also known as BOR2branchio-oto-renal syndrome caused by mutation in SIX5branchiootorenal syndrome type 2SIX5 branchio-oto-renal syndrome
Summary
Branchiootorenal syndrome 2 (MONDO:0012575) is a disease caused by SIX5 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: SIX5 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 158
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | branchiootorenal syndrome 2 |
| Mondo ID | MONDO:0012575 |
| OMIM | 610896 |
| DOID | DOID:0111424 |
| UMLS | C1970479 |
| MedGen | 410081 |
| GARD | 0015503 |
| Is cancer (heuristic) | no |
Also known as: BOR2 · branchio-oto-renal syndrome caused by mutation in SIX5 · branchiootorenal syndrome 2 · branchiootorenal syndrome type 2 · SIX5 branchio-oto-renal syndrome
Data availability: 158 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › branchio-oto-renal syndrome › branchiootorenal syndrome 2
Related subtypes (1): branchiootorenal syndrome 1
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
158 retrieved; paginated sample, class counts are floors:
110 uncertain significance, 21 conflicting classifications of pathogenicity, 15 likely benign, 7 benign/likely benign, 3 benign, 1 likely pathogenic, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 8600 | NM_175875.5(SIX5):c.1093G>A (p.Gly365Arg) | LOC107075317 | Pathogenic | no assertion criteria provided |
| 3899976 | NM_175875.5(SIX5):c.675C>A (p.Tyr225Ter) | DM1-AS | Likely pathogenic | no assertion criteria provided |
| 1317730 | NM_175875.5(SIX5):c.191C>T (p.Pro64Leu) | DM1-AS | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1918598 | NM_175875.5(SIX5):c.628G>A (p.Glu210Lys) | DM1-AS | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2979694 | NM_175875.5(SIX5):c.517G>T (p.Glu173Ter) | DM1-AS | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2987410 | NM_175875.5(SIX5):c.53C>A (p.Ala18Glu) | DM1-AS | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3584024 | NM_175875.5(SIX5):c.288G>A (p.Glu96=) | DM1-AS | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1315682 | NM_175875.5(SIX5):c.1091G>T (p.Gly364Val) | LOC107075317 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2064471 | NM_175875.5(SIX5):c.834C>A (p.Asp278Glu) | LOC107075317 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2359580 | NM_175875.5(SIX5):c.932C>T (p.Pro311Leu) | LOC107075317 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 8599 | NM_175875.5(SIX5):c.886G>A (p.Ala296Thr) | LOC107075317 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1270820 | NM_175875.5(SIX5):c.1651G>A (p.Val551Met) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1360087 | NM_175875.5(SIX5):c.1390A>T (p.Thr464Ser) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2056962 | NM_175875.5(SIX5):c.1739C>T (p.Ala580Val) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2414314 | NM_175875.5(SIX5):c.1342G>C (p.Val448Leu) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2472918 | NM_175875.5(SIX5):c.1321C>T (p.Pro441Ser) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2634151 | NM_175875.5(SIX5):c.1400G>A (p.Ser467Asn) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2650125 | NM_175875.5(SIX5):c.1379C>T (p.Pro460Leu) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3583992 | NM_175875.5(SIX5):c.1223C>A (p.Ala408Asp) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 515611 | NM_175875.5(SIX5):c.1462C>T (p.Pro488Ser) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 829852 | NM_175875.5(SIX5):c.1802C>T (p.Pro601Leu) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 8601 | NM_175875.5(SIX5):c.1655C>T (p.Thr552Met) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 994495 | NM_175875.5(SIX5):c.1687C>T (p.Leu563Phe) | SIX5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1367847 | NM_175875.5(SIX5):c.258C>G (p.Phe86Leu) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2079288 | NM_175875.5(SIX5):c.463G>A (p.Ala155Thr) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2197460 | NM_175875.5(SIX5):c.38C>T (p.Ala13Val) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2435958 | NM_175875.5(SIX5):c.503G>A (p.Arg168His) | DM1-AS | Uncertain significance | criteria provided, single submitter |
| 2884635 | NM_175875.5(SIX5):c.493C>G (p.Leu165Val) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3010143 | NM_175875.5(SIX5):c.347C>G (p.Pro116Arg) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3068352 | NM_175875.5(SIX5):c.668A>G (p.Asn223Ser) | DM1-AS | Uncertain significance | criteria provided, multiple submitters, no conflicts |
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 |
|---|---|---|---|---|
| SIX5 | Definitive | Autosomal dominant | branchiootorenal syndrome 2 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SIX5 | Orphanet:107 | BOR syndrome |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SIX5 | HGNC:10891 | ENSG00000177045 | Q8N196 | Homeobox protein SIX5 | gencc,clinvar |
| DM1-AS | HGNC:53125 | ENSG00000267395 | DM1 locus antisense RNA | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SIX5 | Homeobox protein SIX5 | Transcription factor that is thought to be involved in regulation of organogenesis. |
Protein-family classification
Druggable: 0 · Difficult: 1 · 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 |
|---|---|---|---|
| Transcription factor | 1 | 4.1× | 0.455 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SIX5 | Transcription factor | no | HD, Homeodomain-like_sf, Homeobox_CS | |
| DM1-AS | Other/Unknown | no |
Expression context
Cohort genes with no expression data: 0.
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 |
|---|---|
| right uterine tube | 2 |
| cardiac muscle of right atrium | 1 |
| right ovary | 1 |
| left ovary | 1 |
| right lobe of thyroid gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SIX5 | 205 | ubiquitous | yes | cardiac muscle of right atrium, right uterine tube, right ovary |
| DM1-AS | 157 | broad | yes | right uterine tube, left ovary, right lobe of thyroid gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SIX5 | 1,158 |
| DM1-AS | 0 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 1
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SIX5 | Q8N196 | 53.21 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| Leydig cell proliferation | 1 | 8426.0× | 7e-04 | SIX5 |
| negative regulation of skeletal muscle satellite cell proliferation | 1 | 4213.0× | 7e-04 | SIX5 |
| lens development in camera-type eye | 1 | 374.5× | 0.005 | SIX5 |
| spermatid development | 1 | 145.3× | 0.010 | SIX5 |
| negative regulation of DNA-templated transcription | 1 | 31.6× | 0.038 | SIX5 |
| regulation of transcription by RNA polymerase II | 1 | 11.7× | 0.086 | SIX5 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| SIX5 | 0 | 0 |
| DM1-AS | 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 | 2 | SIX5, DM1-AS |
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) |
|---|---|---|
| SIX5 | 0 | — |
| DM1-AS | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.