Bosley-Salih-Alorainy syndrome

Summary

Bosley-Salih-Alorainy syndrome (MONDO:0019075) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Bosley-Salih-Alorainy syndrome
Mondo ID	MONDO:0019075
Orphanet	69737
ICD-11	1771217937
UMLS	C1832216
MedGen	321908
GARD	0016684
Is cancer (heuristic)	no

Also known as: BSAS

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › human HOXA1 syndromes › Bosley-Salih-Alorainy syndrome

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14898	NM_005522.5(HOXA1):c.175dup (p.Val59fs)	HOXA1	Pathogenic	criteria provided, single submitter
14899	NM_005522.5(HOXA1):c.84C>G (p.Tyr28Ter)	HOXA1	Pathogenic	no assertion criteria provided
14901	NM_005522.5(HOXA1):c.185del (p.Gly62fs)	HOXA1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
HOXA1	Supportive	Autosomal recessive	Bosley-Salih-Alorainy syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOXA1	Orphanet:69737	Bosley-Salih-Alorainy syndrome
HOXA1	Orphanet:69739	Athabaskan brainstem dysgenesis syndrome

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
HOXA1	HGNC:5099	ENSG00000105991	P49639	Homeobox protein Hox-A1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HOXA1	Homeobox protein Hox-A1	Sequence-specific transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HOXA1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

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
esophagus squamous epithelium	1
hair follicle	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOXA1	142	broad	marker	esophagus squamous epithelium, secondary oocyte, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HOXA1	2,373

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HOXA1	P49639	59.15

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
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	91.4×	0.011	HOXA1

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
semicircular canal formation	1	16852.0×	7e-04	HOXA1
optokinetic behavior	1	8426.0×	7e-04	HOXA1
abducens nerve formation	1	8426.0×	7e-04	HOXA1
embryonic neurocranium morphogenesis	1	1872.4×	0.002	HOXA1
outer ear morphogenesis	1	1532.0×	0.002	HOXA1
regulation of behavior	1	1404.3×	0.002	HOXA1
artery development	1	1404.3×	0.002	HOXA1
artery morphogenesis	1	674.1×	0.003	HOXA1
cochlea morphogenesis	1	581.1×	0.003	HOXA1
neuromuscular process	1	526.6×	0.003	HOXA1
cochlea development	1	468.1×	0.003	HOXA1
inner ear development	1	374.5×	0.004	HOXA1
cognition	1	285.6×	0.005	HOXA1
anatomical structure morphogenesis	1	139.3×	0.009	HOXA1
sensory perception of sound	1	100.9×	0.011	HOXA1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	HOXA1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HOXA1

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
HOXA1	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	HOXA1

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)
HOXA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.