Holoprosencephaly 10

Summary

Holoprosencephaly 10 (MONDO:0976262) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	holoprosencephaly 10
Mondo ID	MONDO:0976262
OMIM	621143
GARD	0028099
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › holoprosencephaly › holoprosencephaly 10

Related subtypes (16): holoprosencephaly 3, holoprosencephaly 4, holoprosencephaly 2, holoprosencephaly 1, holoprosencephaly 6, holoprosencephaly 8, holoprosencephaly 7, chromosome 1q41-q42 deletion syndrome, holoprosencephaly 11, microform holoprosencephaly, lobar holoprosencephaly, alobar holoprosencephaly, holoprosencephaly 13, X-linked, holoprosencephaly 14, holoprosencephaly 12 with or without pancreatic agenesis, semilobar holoprosencephaly

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

12 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3776742	DISP1, SER144CYS	DISP1	Pathogenic	no assertion criteria provided
3776743	DISP1, GLN1320TER	DISP1	Pathogenic	no assertion criteria provided
3776744	DISP1, SER746PRO	DISP1	Pathogenic	no assertion criteria provided
3776745	DISP1, PRO189LEU	DISP1	Pathogenic	no assertion criteria provided
3776746	DISP1, GLY1047SER	DISP1	Pathogenic	no assertion criteria provided
3776747	DISP1, 1-BP DEL, NT4408	DISP1	Pathogenic	no assertion criteria provided
4057294	NM_001377229.1(DISP1):c.2064C>A (p.Cys688Ter)	DISP1	Likely pathogenic	criteria provided, single submitter
4845551	NM_001377229.1(DISP1):c.2839G>A (p.Val947Met)	DISP1	Likely pathogenic	criteria provided, single submitter
4849370	NM_001377229.1(DISP1):c.3765del (p.Glu1257fs)	DISP1	Likely pathogenic	criteria provided, single submitter
418828	NM_001377229.1(DISP1):c.3990_3993del (p.His1331fs)	DISP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702962	NM_001377229.1(DISP1):c.4054C>T (p.Pro1352Ser)	DISP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279865	NM_001377229.1(DISP1):c.2165T>A (p.Leu722Gln)	DISP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DISP1	Orphanet:220386	Semilobar holoprosencephaly
DISP1	Orphanet:280195	Septopreoptic holoprosencephaly
DISP1	Orphanet:280200	Microform holoprosencephaly
DISP1	Orphanet:93924	Lobar holoprosencephaly
DISP1	Orphanet:93925	Alobar holoprosencephaly
DISP1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly

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
DISP1	HGNC:19711	ENSG00000154309	Q96F81	Protein dispatched homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DISP1	Protein dispatched homolog 1	Functions in hedgehog (Hh) signaling.

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)
DISP1	Other/Unknown	no		SSD, MMPL_dom, Dispatched_Hh_regulator

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
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DISP1	221	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DISP1	621

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DISP1	Q96F81	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
patched ligand maturation	1	16852.0×	5e-04	DISP1
peptide transport	1	4213.0×	9e-04	DISP1
diaphragm development	1	1872.4×	0.001	DISP1
regulation of protein secretion	1	1532.0×	0.001	DISP1
embryonic pattern specification	1	543.6×	0.003	DISP1
dorsal/ventral pattern formation	1	421.3×	0.003	DISP1
determination of left/right symmetry	1	255.3×	0.004	DISP1
smoothened signaling pathway	1	181.2×	0.006	DISP1

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
DISP1	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	DISP1

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)
DISP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.