deaf blind hypopigmentation syndrome, Yemenite type

Summary

deaf blind hypopigmentation syndrome, Yemenite type (MONDO:0011133) is a disease caused by SOX10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SOX10 (GenCC Definitive)
• Cohort genes: 1
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Very frequent (80-99%)
HP:0000953	Hyperpigmentation of the skin	Very frequent (80-99%)
HP:0001053	Hypopigmented skin patches	Very frequent (80-99%)
HP:0001480	Freckling	Very frequent (80-99%)
HP:0001572	Macrodontia	Very frequent (80-99%)
HP:0005599	Hypopigmentation of hair	Very frequent (80-99%)
HP:0007565	Multiple cafe-au-lait spots	Very frequent (80-99%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000482	Microcornea	Frequent (30-79%)
HP:0000612	Iris coloboma	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0007730	Iris hypopigmentation	Frequent (30-79%)
HP:0011483	Anterior synechiae of the anterior chamber	Frequent (30-79%)
HP:0000679	Taurodontia	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0008499	High hypermetropia	Occasional (5-29%)
HP:0200007	Abnormal size of the palpebral fissures	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	deaf blind hypopigmentation syndrome, Yemenite type
Mondo ID	MONDO:0011133
MeSH	C536771
OMIM	601706
Orphanet	3214
ICD-11	2090985024
SNOMED CT	721084001
UMLS	C1866425
MedGen	355712
GARD	0005535
Is cancer (heuristic)	no

Also known as: Warburg Thomsen syndrome · Warburg-Thomsen syndrome · Yemenite (Warburg) deaf-blind hypopigmentation syndrome · Yemenite deaf-blind hypopigmentation syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › skin pigmentation disorder › hypopigmentation of the skin › deaf blind hypopigmentation syndrome, Yemenite type

Related subtypes (9): Tietz syndrome, piebaldism, piebald trait-neurologic defects syndrome, deafness, congenital, with total albinism, Ito hypomelanosis, albinism-hearing loss syndrome, syndromic oculocutaneous albinism, oculocutaneous albinism, linear hypopigmentation and craniofacial asymmetry with acral, ocular and brain anomalies

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 4 · 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
SOX10	Definitive	Autosomal dominant	deaf blind hypopigmentation syndrome, Yemenite type	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX10	Orphanet:163746	Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease
SOX10	Orphanet:478	Kallmann syndrome
SOX10	Orphanet:895	Waardenburg syndrome type 2
SOX10	Orphanet:897	Waardenburg-Shah 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
SOX10	HGNC:11190	ENSG00000100146	P56693	Transcription factor SOX-10	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX10	Transcription factor SOX-10	Transcription factor that plays a central role in developing and mature glia.

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)
SOX10	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf

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
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX10	218	broad	marker	inferior olivary complex, sural nerve, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX10	3,696

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SOX10	P56693	57.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Regulation of CDH19 Expression and Function	1	1427.5×	0.007	SOX10
Regulation of Homotypic Cell-Cell Adhesion	1	671.8×	0.007	SOX10
Regulation of Expression and Function of Type II Classical Cadherins	1	671.8×	0.007	SOX10
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.008	SOX10
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.008	SOX10
Adherens junctions interactions	1	248.3×	0.008	SOX10
Cell-cell junction organization	1	248.3×	0.008	SOX10
Cell junction organization	1	187.2×	0.008	SOX10
MITF-M-dependent gene expression	1	181.3×	0.008	SOX10
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.008	SOX10
Cell-Cell communication	1	137.6×	0.009	SOX10
MITF-M-regulated melanocyte development	1	114.2×	0.010	SOX10
Nervous system development	1	42.9×	0.025	SOX10
Developmental Biology	1	14.5×	0.069	SOX10

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
positive regulation of gliogenesis	1	8426.0×	0.003	SOX10
morphogenesis of a branching epithelium	1	3370.4×	0.003	SOX10
cellular response to progesterone stimulus	1	2808.7×	0.003	SOX10
negative regulation of Schwann cell proliferation	1	2407.4×	0.003	SOX10
lacrimal gland development	1	2106.5×	0.003	SOX10
central nervous system myelination	1	991.3×	0.004	SOX10
enteric nervous system development	1	991.3×	0.004	SOX10
digestive tract morphogenesis	1	991.3×	0.004	SOX10
melanocyte differentiation	1	802.5×	0.004	SOX10
positive regulation of myelination	1	766.0×	0.004	SOX10
developmental growth	1	732.7×	0.004	SOX10
oligodendrocyte development	1	601.9×	0.004	SOX10
positive regulation of neuroblast proliferation	1	581.1×	0.004	SOX10
peripheral nervous system development	1	581.1×	0.004	SOX10
transcription elongation by RNA polymerase II	1	443.5×	0.004	SOX10
cell maturation	1	443.5×	0.004	SOX10
oligodendrocyte differentiation	1	421.3×	0.004	SOX10
neuroblast proliferation	1	366.4×	0.004	SOX10
morphogenesis of an epithelium	1	343.9×	0.004	SOX10
neural crest cell migration	1	337.0×	0.004	SOX10
cellular response to xenobiotic stimulus	1	240.7×	0.006	SOX10
anatomical structure morphogenesis	1	139.3×	0.009	SOX10
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.011	SOX10
in utero embryonic development	1	72.0×	0.017	SOX10
positive regulation of gene expression	1	38.7×	0.030	SOX10
negative regulation of apoptotic process	1	34.8×	0.032	SOX10
positive regulation of DNA-templated transcription	1	27.9×	0.038	SOX10
negative regulation of transcription by RNA polymerase II	1	17.7×	0.058	SOX10
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SOX10

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
SOX10	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	SOX10

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)
SOX10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.